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Too much to lose from office visit recording or filming
A common phrase you see on inspirational posters is “sing like nobody’s listening, dance like nobody’s watching.”
In medicine, it should be “speak as if everyone is recording, behave as if everyone is filming.”
In this day and age, you’d think that would be obvious. Every few hours there’s a viral video of someone getting upset, then losing their temper and saying something most of us would regret. A few years ago it would be a private matter, but today things are rapidly spread over Facebook and Twitter. Even if it’s entirely false, that doesn’t matter. It’s easy for anyone with a smartphone and apps to edit the clip to make it entirely different from what really happened. People go with their first reaction. By the time the facts come out, they’ve moved on and don’t care about the truth.
Occasionally, I get a request to record what I’m saying. In most cases I decline, and never allow myself to be filmed. I do this because anything can be altered, and unless I go to the effort to record it myself, I have no way to prove who’s telling the truth. So it’s easier just to not do it at all.
Unfortunately, this is often taken as “proof” of me trying to hide something. I’m certainly not. Being open and honest with patients is always something I focus on. But the truth of what happened in a 30- to 60-minute visit can be misconstrued in an edited, and possibly altered, sound bite of 5-10 seconds. People who want to do such things have their own motives and aren’t interested in reason or honesty.
Doctors, like everyone else, are susceptible to human emotions and reactions, but a big part of the job is keeping them controlled and hidden when working with patients. It’s the best way to make reasoned decisions and work with someone who’s frightened, angry, or irrational.
If you find yourself losing the battle to stay in control, sometimes it’s good to remember that your words and actions could be being recorded and posted on Facebook in an hour, whether you permitted it or not. Because you don’t want to learn the hard way.
Dr. Block has a solo neurology practice in Scottsdale, Ariz.
A common phrase you see on inspirational posters is “sing like nobody’s listening, dance like nobody’s watching.”
In medicine, it should be “speak as if everyone is recording, behave as if everyone is filming.”
In this day and age, you’d think that would be obvious. Every few hours there’s a viral video of someone getting upset, then losing their temper and saying something most of us would regret. A few years ago it would be a private matter, but today things are rapidly spread over Facebook and Twitter. Even if it’s entirely false, that doesn’t matter. It’s easy for anyone with a smartphone and apps to edit the clip to make it entirely different from what really happened. People go with their first reaction. By the time the facts come out, they’ve moved on and don’t care about the truth.
Occasionally, I get a request to record what I’m saying. In most cases I decline, and never allow myself to be filmed. I do this because anything can be altered, and unless I go to the effort to record it myself, I have no way to prove who’s telling the truth. So it’s easier just to not do it at all.
Unfortunately, this is often taken as “proof” of me trying to hide something. I’m certainly not. Being open and honest with patients is always something I focus on. But the truth of what happened in a 30- to 60-minute visit can be misconstrued in an edited, and possibly altered, sound bite of 5-10 seconds. People who want to do such things have their own motives and aren’t interested in reason or honesty.
Doctors, like everyone else, are susceptible to human emotions and reactions, but a big part of the job is keeping them controlled and hidden when working with patients. It’s the best way to make reasoned decisions and work with someone who’s frightened, angry, or irrational.
If you find yourself losing the battle to stay in control, sometimes it’s good to remember that your words and actions could be being recorded and posted on Facebook in an hour, whether you permitted it or not. Because you don’t want to learn the hard way.
Dr. Block has a solo neurology practice in Scottsdale, Ariz.
A common phrase you see on inspirational posters is “sing like nobody’s listening, dance like nobody’s watching.”
In medicine, it should be “speak as if everyone is recording, behave as if everyone is filming.”
In this day and age, you’d think that would be obvious. Every few hours there’s a viral video of someone getting upset, then losing their temper and saying something most of us would regret. A few years ago it would be a private matter, but today things are rapidly spread over Facebook and Twitter. Even if it’s entirely false, that doesn’t matter. It’s easy for anyone with a smartphone and apps to edit the clip to make it entirely different from what really happened. People go with their first reaction. By the time the facts come out, they’ve moved on and don’t care about the truth.
Occasionally, I get a request to record what I’m saying. In most cases I decline, and never allow myself to be filmed. I do this because anything can be altered, and unless I go to the effort to record it myself, I have no way to prove who’s telling the truth. So it’s easier just to not do it at all.
Unfortunately, this is often taken as “proof” of me trying to hide something. I’m certainly not. Being open and honest with patients is always something I focus on. But the truth of what happened in a 30- to 60-minute visit can be misconstrued in an edited, and possibly altered, sound bite of 5-10 seconds. People who want to do such things have their own motives and aren’t interested in reason or honesty.
Doctors, like everyone else, are susceptible to human emotions and reactions, but a big part of the job is keeping them controlled and hidden when working with patients. It’s the best way to make reasoned decisions and work with someone who’s frightened, angry, or irrational.
If you find yourself losing the battle to stay in control, sometimes it’s good to remember that your words and actions could be being recorded and posted on Facebook in an hour, whether you permitted it or not. Because you don’t want to learn the hard way.
Dr. Block has a solo neurology practice in Scottsdale, Ariz.
2018 FDA-approved new drugs
In 2018, the Food and Drug Administration approved a record 58 new drugs for humans. One of these agents, Annovera (segesterone acetate and ethinyl estradiol), is a vaginal ring to prevent pregnancy and is not relevant in this article. A second drug, Asparlas (calaspargase pegol-mknl), indicated to treat acute lymphoblastic leukemia, has not yet been released by its manufacturer. The agents with molecular weights (MW) less than 1,000 probably cross the placenta, but nearly all, regardless of MW, will cross in the second half of pregnancy.
There is no human pregnancy data for these agents, but there are five drugs included in pregnancy registries. However, it will take some time before the outcomes of these drugs are published. The routine absence of pregnancy data for most drugs was pointed out in a reference that I coauthored (“Should pregnant women be included in phase 4 clinical drug trials?” Am J Obstet Gynecol. 2015 Dec;213[6]:810-5). The article makes a strong argument for including some drugs in these trials.
Amyloidosis
Onpattro (patisiran) is indicated for the treatment of the polyneuropathy of hereditary transthyretin-mediated amyloidosis in adults. The drug caused embryo-fetal death and reduced fetal body weight in rabbits at doses also associated with maternal toxicity. No developmental toxicity was observed in rats.
Anti-infectives
Aemcolo (rifamycin), which has a MW of 720, is indicated for treatment of travelers’ diarrhea caused by noninvasive strains of Escherichia coli. No adverse fetal effects were observed in rats and rabbits that received close to human doses.
Krintafel (tafenoquine) is an antimalarial agent that is used to prevent relapse in patients who are receiving appropriate antimalarial therapy for Plasmodium vivax infection. The drug may cause hemolytic anemia in a fetus deficient in glucose-6-phosphate dehydrogenase. In rabbits, the drug caused dose-related abortions and maternal toxicity was observed in rabbits and rats. Treatment with this drug in pregnancy is not recommended, according to the manufacturer.
Tpoxx (tecovirimat monohydrate), which has a MW of about 394, is indicated for the treatment of smallpox disease. The drug did not cause embryo-fetal toxicity in pregnant mice and rabbits, but the maximum exposure in rabbits was only 0.4 times the human exposure.
Xofluza (baloxavir marboxil), which has a MW of about 572, is a prodrug that is converted by hydrolysis to baloxavir. It is indicated for the treatment of acute uncomplicated influenza. No adverse developmental effects were observed in rats and rabbits.
Zemdri (plazomicin), which has a MW of about 593, is an aminoglycoside indicated for the treatment of complicated urinary tract infections including pyelonephritis. The drug did not cause fetal harm in rats and rabbits at doses that did not cause maternal toxicity; however, prolonged use of an aminoglycoside (such as streptomycin) has caused irreversible, bilateral congenital deafness in children exposed in utero to prolonged use and is a potential complication.
Three new drugs in 2018 are indicated for treating HIV-1:
Biktarvy is a three-drug combination that includes bictegravir, emtricitabine, and tenofovir. The latter two drugs are included in the 11th edition of my book (“Drugs in Pregnancy and Lactation,” 11th ed. [Riverwoods, Ill.: Wolters Kluwer, 2017) and are not included here. Both are classified as compatible in pregnancy. Bictegravir has a MW of about 471. No adverse embryo-fetal effects in rats and rabbits were observed with this agent.
Trogarzo (ibalizumab-uiyk), which has a MW of about 150,000, is a monoclonal antibody antiretroviral agent used in combination with other antiretrovirals. There are no animal data. Although the MW is very high, monoclonal antibodies are transported across the placenta as pregnancy progresses.
Pifeltro (doravirine), which has a MW of about 426, is a nonnucleoside reverse transcriptase inhibitor used in combination with other antiretroviral agents for the treatment of HIV-1. The drug caused no significant toxicologic effects on embryo-fetal rats and rabbits.
If Biktarvy, Pifeltro, or Trogarzo are used in pregnancy, health care providers are encouraged to register the patient in the Antiretroviral Pregnancy Registry by calling 1-800-258-4263.
There are three new agents in the tetracycline class.
Nuzyra (omadacycline), which has a MW of about 729, is for community-acquired bacterial pneumonia and acute bacterial skin and skin structure infections.
Seysara (sarecycline), which has a MW of about 524, is for inflammatory lesions of nonnodular, moderate to severe acne vulgaris.
Xerava (eravacycline), which has a MW of about 632, is for complicated intra-abdominal infection.
The various dose-related toxicities observed with the three drugs in rats and rabbits included maternal deaths; increased postimplantation loss; reduced fetal body weights; delays in skeletal ossification; and fetal malformations of the skeleton, heart, and lung. Use of these drugs in the last half of pregnancy may cause permanent discoloration of the teeth and enamel hypoplasia, as well as inhibition of bone growth.
Antilipemic agents
Crysvita (burosumab-twza), which has a MW of about 147,000, is a fibroblast growth factor–blocking antibody indicated for the treatment of X-linked hypophosphatemia. In pregnant cynomolgus monkeys, doses slightly higher than the human dose were not teratogenic. The drug was detected in fetal serum indicating that it crossed the monkey placenta.
Tegsedi (inotersen), which has a MW of about 7,601, is an amyloidosis inhibitor used for polyneuropathy of hereditary transthyretin-mediated amyloidosis. It is available only through a restricted program. The drug was not teratogenic in mice and rabbits; however, it does decrease vitamin A levels, so supplementation with the vitamin is recommended.
Antineoplastics
The manufacturers recommend avoiding these drugs during pregnancy. Effective contraception should be used.
Daurismo (glasdegib), which has a MW of about 491, is a hedgehog pathway inhibitor indicated in combination with low-dose cytarabine for newly diagnosed acute myeloid leukemia (AML). The drug caused embryotoxicity, fetotoxicity, and teratogenicity in rats and rabbits at doses less than the human dose.
Erleada (apalutamide), which has a MW of about 477, is an androgen receptor inhibitor indicated for nonmetastatic, castration-resistant prostate cancer. Animal studies were not conducted because the drug should not be used in females.
Elzonris (tagraxofusp-erzs), which has a MW of 57,695, is a cytotoxin indicated for the treatment of blastic plasmacytoid dendritic cell neoplasm. Animal studies have not been conducted.
Lumoxiti (moxetumomab pasudotox–tdfk) which as a MW of about 63,000, is indicated for relapsed or refractory hairy cell leukemia. Studies have not been conducted in pregnant animals. Two life-threatening outcomes have occurred with the drug: capillary leak syndrome and hemolytic uremic syndrome. The drug should be discontinued if either occurs.
Lutathera (lutetium Lu 177 dotatate), which has a MW of about 1,610, is a radiolabeled somatostatin analogue given as a single intravenous dose every 8 weeks for four doses for the treatment of gastroenteropancreatic neuroendocrine tumors. Reproductive studies in animals have not been conducted. However, all radiopharmaceuticals have the potential to cause embryo-fetal harm. They also can cause infertility in males and females.
Talzenna (talazoparib), which has a MW of about 553, is a poly (ADP-ribose) polymerase inhibitor indicated for the treatment of certain types of breast cancer. At doses much less then the human dose, the drug caused fetal malformations and embryo-fetal death in rats.
Tibsovo (ivosidenib), which has a MW of 583, is an isocitrate dehydrogenase 1 inhibitor used for patients with relapsed or refractory AML. The drug caused embryo-fetal toxicity in rats and rabbits at doses slighter higher than the human dose.
There are seven new kinase inhibitors.
Braftovi (encorafenib), which has a MW of 540, is indicated in combination with Mektovi for patients with a specific type of metastatic melanoma. The drug caused embryo-fetal toxicity in rats and rabbits.
Copiktra (duvelisib), which has a MW of about 435, is indicated for treatment of chronic lymphocytic leukemia and follicular lymphoma. In rats and rabbits, the drug caused embryo-fetal death, lower fetal weights, and malformations.
Lorbrena (lorlatinib), which has a MW of about 406, is given for the treatment of metastatic non–small cell lung cancer. In rats and rabbits, the drug caused abortions, decreased fetal body weight, and major malformations.
Mektovi (binimetinib), which has a MW of about 441, is used in combination with Braftovi for patients with a specific type of melanoma. The drug was embryotoxic and abortifacient in rabbits.
Vitrakvi (larotrectinib), which has a MW of about 527, is used for patients with solid tumors. Studies in rats revealed fetal anasarca (extreme generalized edema) and omphalocele in rabbits.
Vizimpro (dacomitinib), which has a MW of about 488, is indicated for metastatic non–small cell lung cancer. The drug caused embryo-fetal toxicity in rats and mice.
Xospata (gilteritinib), which has a MW of about 1,222, is indicated for relapsed or refractory AML. In rats, the drug caused embryo-fetal death, suppressed fetal growth, and caused multiple malformations.
Three drugs are classified as monoclonal antibodies.
Gamifant (emapalumab), which has a MW of about 148,000, is indicated for primary hemophagocytic lymphohistiocytosis. A murine surrogate antimouse antibody was given to pregnant mice throughout gestation and no fetal harm was observed.
Libtayo (cemiplimab-rwlc), which has a MW of 146,000, is indicated for patients with metastatic or locally advanced cutaneous squamous cell carcinoma. Animal reproduction studies have not been conducted; however, based on its mechanism, increased rates of abortion or stillbirth may occur if the drug is used in human pregnancy.
Poteligeo (mogamulizumab-kpkc), which has a MW of about 149,000, is given for relapsed/refractory mycosis fungoides or Sézary syndrome. In pregnant monkeys, there was no embryo-fetal lethality, teratogenicity, fetal growth restriction, spontaneous abortion, or increased fetal death.
Central nervous system
There are three antimigraine agents that are monoclonal antibodies given as a subcutaneous injection.
Aimovig (erenumab-aooe), which has a MW of about 150,000, caused no adverse effects in monkey offspring.
Ajovy (fremanezumab-vfrm), which has a MW of about 148,000, had no adverse effect in rat and rabbit offspring.
Emgality (galcanezumab-gnlm), which has a MW of about 147,000, produced no adverse effects in rat and rabbit offspring.
Diacomit (stiripentol), which has a MW of about 234, is an anticonvulsant used to treat seizures associated with Dravet syndrome. The drug caused severe embryo-fetal toxicity in mice, rabbits, and rats. The drug is included in the North American Antiepileptic Drug (NAAED) Pregnancy Registry. Patients can enroll themselves by calling the toll-free number 1-888-233-2334 or visiting http://aedpregnancyregistry.org/.
Epidiolex (cannabidiol), which has a MW of about 314, is an anticonvulsant indicated for the treatment of seizures associated with Lennox-Gastaut syndrome or Dravet syndrome. In pregnant rats, doses up to about 16 times the recommended human dose (RHD) caused no embryo-fetal adverse effects. The drug caused decreased fetal body weights, increased fetal structural variations, and maternal toxicity when the drug was given to pregnant rabbits throughout organogenesis. The no-effect dose for embryo-fetal toxicity was less than the human dose. Patients can enroll themselves in the NAAED Pregnancy Registry by calling the toll-free number 1-888-233-2334 or visiting http://aedpregnancyregistry.org/.
Firdapse (amifampridine), a potassium channel blocker with a MW of about 201, is used for the treatment of Lambert-Eaton myasthenic syndrome. No adverse effects on embryo-fetal development were observed in rats and rabbits given the drug throughout organogenesis. However, in rats given the drug throughout pregnancy and lactation, there was an increase in stillbirths and pup deaths, reduced pup weight, and delayed sexual development in female pups.
Lucemyra (lofexidine), which has a MW of about 296, is used to mitigate opioid withdrawal symptoms to facilitate abrupt opioid discontinuation in adults. The drug caused severe toxicity in the fetuses of rats and rabbits.
Olumiant (baricitinib), which has a MW of about 371, is a Janus kinase inhibitor indicated for the treatment of rheumatoid arthritis. The drug was teratogenic in pregnant rats given doses about 20 times greater than the maximum RHD based on area under the curve. In rabbits, embryo death and rib anomalies were observed with doses 84 times greater than the maximum RHD, but no developmental toxicity was seen with doses 12 times greater than the maximum RHD.
Orilissa (elagolix), which has a MW of about 654, is a gonadotropin-releasing hormone receptor antagonist indicated for the management of pain associated with endometriosis. The drug caused abortions in rats and rabbits. Because the drug may increase the risk of early pregnancy loss, the manufacturer classifies it as contraindicated in pregnancy.
Dermatologic agents
Ilumya (tildrakizumab), which has a MW of about 147,000, is given by subcutaneous injection for the treatment of moderate to severe plaque psoriasis. When given during organogenesis in monkeys, no maternal or embryo-fetal toxicities were observed. However, when given throughout pregnancy a few neonatal deaths occurred, but the clinical significance of these nonclinical findings were unknown.
Fabry disease
Galafold (migalastat), which has a MW of about 200, is an alpha-galactosidase A pharmacologic chaperone indicated for the treatment of Fabry disease. Three pregnant women with Fabry disease were exposed to the drug in clinical studies but no information was provided on the pregnancy outcomes. No adverse developmental effects were observed in pregnant rats and rabbits.
Gastrointestinal agents
Akynzeo (netupitant or fosnetupitant palonosetron), which have MWs of about 579, 333, and 762, respectively, is available as an oral capsule (netupitant + palonosetron) and as an intravenous formulation (fosnetupitant + palonosetron). They are indicated, in combination with dexamethasone, for the prevention of nausea and vomiting related to cancer chemotherapy. Netupitant and fosnetupitant produced no embryo-fetal adverse effects in rats but were toxic to rabbit embryos. Palonosetron caused no embryo-fetal adverse effects in rats and rabbits.
Motegrity (prucalopride), which has a MW of about 486, is indicated for chronic idiopathic constipation. No adverse embryo-fetal developmental effects were observed in rats and rabbits.
Hematologic agents
Doptelet (avatrombopag), which has a MW of about 766, is indicated for the treatment of thrombocytopenia in adult patients with chronic liver disease who are scheduled to undergo a procedure. No embryo-fetal effects were observed in rats, but in rabbits the drug was associated with spontaneous abortions.
Lokelma (sodium zirconium cyclosilicate) is a nonabsorbed zirconium silicate that exchanges potassium for hydrogen and sodium. Animal studies have not been conducted. Because it is not absorbed, it is not expected to result in fetal exposure to the drug.
Mulpleta (lusutrombopag), which has a MW of about 592, a thrombopoietin receptor agonist, is indicated for the treatment of thrombocytopenia in patients with chronic liver disease. High levels of the drug in pregnant rats were associated with adverse developmental outcomes. No adverse embryo-fetal effects were seen in pregnant rabbits.
Palynziq (pegvaliase-pqpz), which has a MW of about 1,000,000, is a phenylalanine-metabolizing enzyme indicated to reduce blood phenylalanine concentrations in patients with phenylketonuria. In pregnant rats, the drug caused an increase in skeletal variations. In rabbits, the drug caused a high incidence of multiple malformations.
Takhzyro (lanadelumab-flyo), which has a MW of about 49,000, is a monoclonal antibody indicated for prophylaxis to prevent attacks of hereditary angioedema. The drug caused no fetal harm in monkeys.
Tavalisse (fostamatinib disodium hexahydrate), which has a MW of about 733, is a kinase inhibitor used for the treatment of thrombocytopenia. In pregnant rats and rabbits, the drug caused adverse developmental outcomes including embryo-fetal mortality, lower fetal weights, and structural anomalies.
Ultomiris (ravulizumab), which has a MW of about 148,000, is a humanized monoclonal antibody indicated for adult patients with paroxysmal nocturnal hemoglobinuria. In mice, the drug was associated with increased rates of developmental abnormalities and an increased rate of dead and moribund offspring.
Immunologic agent
Revcovi (elapegademase-lvlr), which has a MW of about 113,000, is a recombinant adenosine deaminase indicated for the treatment of adenosine deaminase severe combined immune deficiency. Animal studies in pregnancy have not been conducted.
Nutrient/Nutritional supplement
Fish oil is indicated as a source of calories and fatty acids in pediatric patients with parenteral nutrition-associated cholestasis. Animal reproduction studies have not been conducted. It is doubtful if this product will be used in pregnancy.
Ophthalmic – nerve growth factor
Oxervate (cenegermin-bkbj), which has a MW of 13,266, is a solution that contains 118 amino acids. It is a recombinant human nerve growth factor indicated for neurotrophic keratitis. In rats and rabbits given the drug during organogenesis, there was a slight increase in postimplantation loss at doses greater than or equal to 267 times the human dose.
Respiratory drugs
Symdeko (tezacaftor + ivacaftor), which have MWs of about 521 and 392, is indicated for the treatment of patients with cystic fibrosis who are homozygous for the F508del mutation or who have at least one mutation in the cystic fibrosis transmembrane conductance regulator gene. There were no adverse developmental effects in pregnant rats and rabbits when the drugs were used separately or combined.
Yupelri (revefenacin), which has a MW of about 598, is an anticholinergic drug. It is an inhaled solution for the maintenance treatment of chronic obstructive pulmonary disease. In rats and rabbits, doses that were about 209 times the RHD produced no evidence of fetal harm.
Mr. Briggs is clinical professor of pharmacy at the University of California, San Francisco, and adjunct professor of pharmacy at the University of Southern California, Los Angeles, as well as at Washington State University, Spokane. Mr. Briggs reported no relevant financial disclosures. Email him at obnews@mdedge.com.
In 2018, the Food and Drug Administration approved a record 58 new drugs for humans. One of these agents, Annovera (segesterone acetate and ethinyl estradiol), is a vaginal ring to prevent pregnancy and is not relevant in this article. A second drug, Asparlas (calaspargase pegol-mknl), indicated to treat acute lymphoblastic leukemia, has not yet been released by its manufacturer. The agents with molecular weights (MW) less than 1,000 probably cross the placenta, but nearly all, regardless of MW, will cross in the second half of pregnancy.
There is no human pregnancy data for these agents, but there are five drugs included in pregnancy registries. However, it will take some time before the outcomes of these drugs are published. The routine absence of pregnancy data for most drugs was pointed out in a reference that I coauthored (“Should pregnant women be included in phase 4 clinical drug trials?” Am J Obstet Gynecol. 2015 Dec;213[6]:810-5). The article makes a strong argument for including some drugs in these trials.
Amyloidosis
Onpattro (patisiran) is indicated for the treatment of the polyneuropathy of hereditary transthyretin-mediated amyloidosis in adults. The drug caused embryo-fetal death and reduced fetal body weight in rabbits at doses also associated with maternal toxicity. No developmental toxicity was observed in rats.
Anti-infectives
Aemcolo (rifamycin), which has a MW of 720, is indicated for treatment of travelers’ diarrhea caused by noninvasive strains of Escherichia coli. No adverse fetal effects were observed in rats and rabbits that received close to human doses.
Krintafel (tafenoquine) is an antimalarial agent that is used to prevent relapse in patients who are receiving appropriate antimalarial therapy for Plasmodium vivax infection. The drug may cause hemolytic anemia in a fetus deficient in glucose-6-phosphate dehydrogenase. In rabbits, the drug caused dose-related abortions and maternal toxicity was observed in rabbits and rats. Treatment with this drug in pregnancy is not recommended, according to the manufacturer.
Tpoxx (tecovirimat monohydrate), which has a MW of about 394, is indicated for the treatment of smallpox disease. The drug did not cause embryo-fetal toxicity in pregnant mice and rabbits, but the maximum exposure in rabbits was only 0.4 times the human exposure.
Xofluza (baloxavir marboxil), which has a MW of about 572, is a prodrug that is converted by hydrolysis to baloxavir. It is indicated for the treatment of acute uncomplicated influenza. No adverse developmental effects were observed in rats and rabbits.
Zemdri (plazomicin), which has a MW of about 593, is an aminoglycoside indicated for the treatment of complicated urinary tract infections including pyelonephritis. The drug did not cause fetal harm in rats and rabbits at doses that did not cause maternal toxicity; however, prolonged use of an aminoglycoside (such as streptomycin) has caused irreversible, bilateral congenital deafness in children exposed in utero to prolonged use and is a potential complication.
Three new drugs in 2018 are indicated for treating HIV-1:
Biktarvy is a three-drug combination that includes bictegravir, emtricitabine, and tenofovir. The latter two drugs are included in the 11th edition of my book (“Drugs in Pregnancy and Lactation,” 11th ed. [Riverwoods, Ill.: Wolters Kluwer, 2017) and are not included here. Both are classified as compatible in pregnancy. Bictegravir has a MW of about 471. No adverse embryo-fetal effects in rats and rabbits were observed with this agent.
Trogarzo (ibalizumab-uiyk), which has a MW of about 150,000, is a monoclonal antibody antiretroviral agent used in combination with other antiretrovirals. There are no animal data. Although the MW is very high, monoclonal antibodies are transported across the placenta as pregnancy progresses.
Pifeltro (doravirine), which has a MW of about 426, is a nonnucleoside reverse transcriptase inhibitor used in combination with other antiretroviral agents for the treatment of HIV-1. The drug caused no significant toxicologic effects on embryo-fetal rats and rabbits.
If Biktarvy, Pifeltro, or Trogarzo are used in pregnancy, health care providers are encouraged to register the patient in the Antiretroviral Pregnancy Registry by calling 1-800-258-4263.
There are three new agents in the tetracycline class.
Nuzyra (omadacycline), which has a MW of about 729, is for community-acquired bacterial pneumonia and acute bacterial skin and skin structure infections.
Seysara (sarecycline), which has a MW of about 524, is for inflammatory lesions of nonnodular, moderate to severe acne vulgaris.
Xerava (eravacycline), which has a MW of about 632, is for complicated intra-abdominal infection.
The various dose-related toxicities observed with the three drugs in rats and rabbits included maternal deaths; increased postimplantation loss; reduced fetal body weights; delays in skeletal ossification; and fetal malformations of the skeleton, heart, and lung. Use of these drugs in the last half of pregnancy may cause permanent discoloration of the teeth and enamel hypoplasia, as well as inhibition of bone growth.
Antilipemic agents
Crysvita (burosumab-twza), which has a MW of about 147,000, is a fibroblast growth factor–blocking antibody indicated for the treatment of X-linked hypophosphatemia. In pregnant cynomolgus monkeys, doses slightly higher than the human dose were not teratogenic. The drug was detected in fetal serum indicating that it crossed the monkey placenta.
Tegsedi (inotersen), which has a MW of about 7,601, is an amyloidosis inhibitor used for polyneuropathy of hereditary transthyretin-mediated amyloidosis. It is available only through a restricted program. The drug was not teratogenic in mice and rabbits; however, it does decrease vitamin A levels, so supplementation with the vitamin is recommended.
Antineoplastics
The manufacturers recommend avoiding these drugs during pregnancy. Effective contraception should be used.
Daurismo (glasdegib), which has a MW of about 491, is a hedgehog pathway inhibitor indicated in combination with low-dose cytarabine for newly diagnosed acute myeloid leukemia (AML). The drug caused embryotoxicity, fetotoxicity, and teratogenicity in rats and rabbits at doses less than the human dose.
Erleada (apalutamide), which has a MW of about 477, is an androgen receptor inhibitor indicated for nonmetastatic, castration-resistant prostate cancer. Animal studies were not conducted because the drug should not be used in females.
Elzonris (tagraxofusp-erzs), which has a MW of 57,695, is a cytotoxin indicated for the treatment of blastic plasmacytoid dendritic cell neoplasm. Animal studies have not been conducted.
Lumoxiti (moxetumomab pasudotox–tdfk) which as a MW of about 63,000, is indicated for relapsed or refractory hairy cell leukemia. Studies have not been conducted in pregnant animals. Two life-threatening outcomes have occurred with the drug: capillary leak syndrome and hemolytic uremic syndrome. The drug should be discontinued if either occurs.
Lutathera (lutetium Lu 177 dotatate), which has a MW of about 1,610, is a radiolabeled somatostatin analogue given as a single intravenous dose every 8 weeks for four doses for the treatment of gastroenteropancreatic neuroendocrine tumors. Reproductive studies in animals have not been conducted. However, all radiopharmaceuticals have the potential to cause embryo-fetal harm. They also can cause infertility in males and females.
Talzenna (talazoparib), which has a MW of about 553, is a poly (ADP-ribose) polymerase inhibitor indicated for the treatment of certain types of breast cancer. At doses much less then the human dose, the drug caused fetal malformations and embryo-fetal death in rats.
Tibsovo (ivosidenib), which has a MW of 583, is an isocitrate dehydrogenase 1 inhibitor used for patients with relapsed or refractory AML. The drug caused embryo-fetal toxicity in rats and rabbits at doses slighter higher than the human dose.
There are seven new kinase inhibitors.
Braftovi (encorafenib), which has a MW of 540, is indicated in combination with Mektovi for patients with a specific type of metastatic melanoma. The drug caused embryo-fetal toxicity in rats and rabbits.
Copiktra (duvelisib), which has a MW of about 435, is indicated for treatment of chronic lymphocytic leukemia and follicular lymphoma. In rats and rabbits, the drug caused embryo-fetal death, lower fetal weights, and malformations.
Lorbrena (lorlatinib), which has a MW of about 406, is given for the treatment of metastatic non–small cell lung cancer. In rats and rabbits, the drug caused abortions, decreased fetal body weight, and major malformations.
Mektovi (binimetinib), which has a MW of about 441, is used in combination with Braftovi for patients with a specific type of melanoma. The drug was embryotoxic and abortifacient in rabbits.
Vitrakvi (larotrectinib), which has a MW of about 527, is used for patients with solid tumors. Studies in rats revealed fetal anasarca (extreme generalized edema) and omphalocele in rabbits.
Vizimpro (dacomitinib), which has a MW of about 488, is indicated for metastatic non–small cell lung cancer. The drug caused embryo-fetal toxicity in rats and mice.
Xospata (gilteritinib), which has a MW of about 1,222, is indicated for relapsed or refractory AML. In rats, the drug caused embryo-fetal death, suppressed fetal growth, and caused multiple malformations.
Three drugs are classified as monoclonal antibodies.
Gamifant (emapalumab), which has a MW of about 148,000, is indicated for primary hemophagocytic lymphohistiocytosis. A murine surrogate antimouse antibody was given to pregnant mice throughout gestation and no fetal harm was observed.
Libtayo (cemiplimab-rwlc), which has a MW of 146,000, is indicated for patients with metastatic or locally advanced cutaneous squamous cell carcinoma. Animal reproduction studies have not been conducted; however, based on its mechanism, increased rates of abortion or stillbirth may occur if the drug is used in human pregnancy.
Poteligeo (mogamulizumab-kpkc), which has a MW of about 149,000, is given for relapsed/refractory mycosis fungoides or Sézary syndrome. In pregnant monkeys, there was no embryo-fetal lethality, teratogenicity, fetal growth restriction, spontaneous abortion, or increased fetal death.
Central nervous system
There are three antimigraine agents that are monoclonal antibodies given as a subcutaneous injection.
Aimovig (erenumab-aooe), which has a MW of about 150,000, caused no adverse effects in monkey offspring.
Ajovy (fremanezumab-vfrm), which has a MW of about 148,000, had no adverse effect in rat and rabbit offspring.
Emgality (galcanezumab-gnlm), which has a MW of about 147,000, produced no adverse effects in rat and rabbit offspring.
Diacomit (stiripentol), which has a MW of about 234, is an anticonvulsant used to treat seizures associated with Dravet syndrome. The drug caused severe embryo-fetal toxicity in mice, rabbits, and rats. The drug is included in the North American Antiepileptic Drug (NAAED) Pregnancy Registry. Patients can enroll themselves by calling the toll-free number 1-888-233-2334 or visiting http://aedpregnancyregistry.org/.
Epidiolex (cannabidiol), which has a MW of about 314, is an anticonvulsant indicated for the treatment of seizures associated with Lennox-Gastaut syndrome or Dravet syndrome. In pregnant rats, doses up to about 16 times the recommended human dose (RHD) caused no embryo-fetal adverse effects. The drug caused decreased fetal body weights, increased fetal structural variations, and maternal toxicity when the drug was given to pregnant rabbits throughout organogenesis. The no-effect dose for embryo-fetal toxicity was less than the human dose. Patients can enroll themselves in the NAAED Pregnancy Registry by calling the toll-free number 1-888-233-2334 or visiting http://aedpregnancyregistry.org/.
Firdapse (amifampridine), a potassium channel blocker with a MW of about 201, is used for the treatment of Lambert-Eaton myasthenic syndrome. No adverse effects on embryo-fetal development were observed in rats and rabbits given the drug throughout organogenesis. However, in rats given the drug throughout pregnancy and lactation, there was an increase in stillbirths and pup deaths, reduced pup weight, and delayed sexual development in female pups.
Lucemyra (lofexidine), which has a MW of about 296, is used to mitigate opioid withdrawal symptoms to facilitate abrupt opioid discontinuation in adults. The drug caused severe toxicity in the fetuses of rats and rabbits.
Olumiant (baricitinib), which has a MW of about 371, is a Janus kinase inhibitor indicated for the treatment of rheumatoid arthritis. The drug was teratogenic in pregnant rats given doses about 20 times greater than the maximum RHD based on area under the curve. In rabbits, embryo death and rib anomalies were observed with doses 84 times greater than the maximum RHD, but no developmental toxicity was seen with doses 12 times greater than the maximum RHD.
Orilissa (elagolix), which has a MW of about 654, is a gonadotropin-releasing hormone receptor antagonist indicated for the management of pain associated with endometriosis. The drug caused abortions in rats and rabbits. Because the drug may increase the risk of early pregnancy loss, the manufacturer classifies it as contraindicated in pregnancy.
Dermatologic agents
Ilumya (tildrakizumab), which has a MW of about 147,000, is given by subcutaneous injection for the treatment of moderate to severe plaque psoriasis. When given during organogenesis in monkeys, no maternal or embryo-fetal toxicities were observed. However, when given throughout pregnancy a few neonatal deaths occurred, but the clinical significance of these nonclinical findings were unknown.
Fabry disease
Galafold (migalastat), which has a MW of about 200, is an alpha-galactosidase A pharmacologic chaperone indicated for the treatment of Fabry disease. Three pregnant women with Fabry disease were exposed to the drug in clinical studies but no information was provided on the pregnancy outcomes. No adverse developmental effects were observed in pregnant rats and rabbits.
Gastrointestinal agents
Akynzeo (netupitant or fosnetupitant palonosetron), which have MWs of about 579, 333, and 762, respectively, is available as an oral capsule (netupitant + palonosetron) and as an intravenous formulation (fosnetupitant + palonosetron). They are indicated, in combination with dexamethasone, for the prevention of nausea and vomiting related to cancer chemotherapy. Netupitant and fosnetupitant produced no embryo-fetal adverse effects in rats but were toxic to rabbit embryos. Palonosetron caused no embryo-fetal adverse effects in rats and rabbits.
Motegrity (prucalopride), which has a MW of about 486, is indicated for chronic idiopathic constipation. No adverse embryo-fetal developmental effects were observed in rats and rabbits.
Hematologic agents
Doptelet (avatrombopag), which has a MW of about 766, is indicated for the treatment of thrombocytopenia in adult patients with chronic liver disease who are scheduled to undergo a procedure. No embryo-fetal effects were observed in rats, but in rabbits the drug was associated with spontaneous abortions.
Lokelma (sodium zirconium cyclosilicate) is a nonabsorbed zirconium silicate that exchanges potassium for hydrogen and sodium. Animal studies have not been conducted. Because it is not absorbed, it is not expected to result in fetal exposure to the drug.
Mulpleta (lusutrombopag), which has a MW of about 592, a thrombopoietin receptor agonist, is indicated for the treatment of thrombocytopenia in patients with chronic liver disease. High levels of the drug in pregnant rats were associated with adverse developmental outcomes. No adverse embryo-fetal effects were seen in pregnant rabbits.
Palynziq (pegvaliase-pqpz), which has a MW of about 1,000,000, is a phenylalanine-metabolizing enzyme indicated to reduce blood phenylalanine concentrations in patients with phenylketonuria. In pregnant rats, the drug caused an increase in skeletal variations. In rabbits, the drug caused a high incidence of multiple malformations.
Takhzyro (lanadelumab-flyo), which has a MW of about 49,000, is a monoclonal antibody indicated for prophylaxis to prevent attacks of hereditary angioedema. The drug caused no fetal harm in monkeys.
Tavalisse (fostamatinib disodium hexahydrate), which has a MW of about 733, is a kinase inhibitor used for the treatment of thrombocytopenia. In pregnant rats and rabbits, the drug caused adverse developmental outcomes including embryo-fetal mortality, lower fetal weights, and structural anomalies.
Ultomiris (ravulizumab), which has a MW of about 148,000, is a humanized monoclonal antibody indicated for adult patients with paroxysmal nocturnal hemoglobinuria. In mice, the drug was associated with increased rates of developmental abnormalities and an increased rate of dead and moribund offspring.
Immunologic agent
Revcovi (elapegademase-lvlr), which has a MW of about 113,000, is a recombinant adenosine deaminase indicated for the treatment of adenosine deaminase severe combined immune deficiency. Animal studies in pregnancy have not been conducted.
Nutrient/Nutritional supplement
Fish oil is indicated as a source of calories and fatty acids in pediatric patients with parenteral nutrition-associated cholestasis. Animal reproduction studies have not been conducted. It is doubtful if this product will be used in pregnancy.
Ophthalmic – nerve growth factor
Oxervate (cenegermin-bkbj), which has a MW of 13,266, is a solution that contains 118 amino acids. It is a recombinant human nerve growth factor indicated for neurotrophic keratitis. In rats and rabbits given the drug during organogenesis, there was a slight increase in postimplantation loss at doses greater than or equal to 267 times the human dose.
Respiratory drugs
Symdeko (tezacaftor + ivacaftor), which have MWs of about 521 and 392, is indicated for the treatment of patients with cystic fibrosis who are homozygous for the F508del mutation or who have at least one mutation in the cystic fibrosis transmembrane conductance regulator gene. There were no adverse developmental effects in pregnant rats and rabbits when the drugs were used separately or combined.
Yupelri (revefenacin), which has a MW of about 598, is an anticholinergic drug. It is an inhaled solution for the maintenance treatment of chronic obstructive pulmonary disease. In rats and rabbits, doses that were about 209 times the RHD produced no evidence of fetal harm.
Mr. Briggs is clinical professor of pharmacy at the University of California, San Francisco, and adjunct professor of pharmacy at the University of Southern California, Los Angeles, as well as at Washington State University, Spokane. Mr. Briggs reported no relevant financial disclosures. Email him at obnews@mdedge.com.
In 2018, the Food and Drug Administration approved a record 58 new drugs for humans. One of these agents, Annovera (segesterone acetate and ethinyl estradiol), is a vaginal ring to prevent pregnancy and is not relevant in this article. A second drug, Asparlas (calaspargase pegol-mknl), indicated to treat acute lymphoblastic leukemia, has not yet been released by its manufacturer. The agents with molecular weights (MW) less than 1,000 probably cross the placenta, but nearly all, regardless of MW, will cross in the second half of pregnancy.
There is no human pregnancy data for these agents, but there are five drugs included in pregnancy registries. However, it will take some time before the outcomes of these drugs are published. The routine absence of pregnancy data for most drugs was pointed out in a reference that I coauthored (“Should pregnant women be included in phase 4 clinical drug trials?” Am J Obstet Gynecol. 2015 Dec;213[6]:810-5). The article makes a strong argument for including some drugs in these trials.
Amyloidosis
Onpattro (patisiran) is indicated for the treatment of the polyneuropathy of hereditary transthyretin-mediated amyloidosis in adults. The drug caused embryo-fetal death and reduced fetal body weight in rabbits at doses also associated with maternal toxicity. No developmental toxicity was observed in rats.
Anti-infectives
Aemcolo (rifamycin), which has a MW of 720, is indicated for treatment of travelers’ diarrhea caused by noninvasive strains of Escherichia coli. No adverse fetal effects were observed in rats and rabbits that received close to human doses.
Krintafel (tafenoquine) is an antimalarial agent that is used to prevent relapse in patients who are receiving appropriate antimalarial therapy for Plasmodium vivax infection. The drug may cause hemolytic anemia in a fetus deficient in glucose-6-phosphate dehydrogenase. In rabbits, the drug caused dose-related abortions and maternal toxicity was observed in rabbits and rats. Treatment with this drug in pregnancy is not recommended, according to the manufacturer.
Tpoxx (tecovirimat monohydrate), which has a MW of about 394, is indicated for the treatment of smallpox disease. The drug did not cause embryo-fetal toxicity in pregnant mice and rabbits, but the maximum exposure in rabbits was only 0.4 times the human exposure.
Xofluza (baloxavir marboxil), which has a MW of about 572, is a prodrug that is converted by hydrolysis to baloxavir. It is indicated for the treatment of acute uncomplicated influenza. No adverse developmental effects were observed in rats and rabbits.
Zemdri (plazomicin), which has a MW of about 593, is an aminoglycoside indicated for the treatment of complicated urinary tract infections including pyelonephritis. The drug did not cause fetal harm in rats and rabbits at doses that did not cause maternal toxicity; however, prolonged use of an aminoglycoside (such as streptomycin) has caused irreversible, bilateral congenital deafness in children exposed in utero to prolonged use and is a potential complication.
Three new drugs in 2018 are indicated for treating HIV-1:
Biktarvy is a three-drug combination that includes bictegravir, emtricitabine, and tenofovir. The latter two drugs are included in the 11th edition of my book (“Drugs in Pregnancy and Lactation,” 11th ed. [Riverwoods, Ill.: Wolters Kluwer, 2017) and are not included here. Both are classified as compatible in pregnancy. Bictegravir has a MW of about 471. No adverse embryo-fetal effects in rats and rabbits were observed with this agent.
Trogarzo (ibalizumab-uiyk), which has a MW of about 150,000, is a monoclonal antibody antiretroviral agent used in combination with other antiretrovirals. There are no animal data. Although the MW is very high, monoclonal antibodies are transported across the placenta as pregnancy progresses.
Pifeltro (doravirine), which has a MW of about 426, is a nonnucleoside reverse transcriptase inhibitor used in combination with other antiretroviral agents for the treatment of HIV-1. The drug caused no significant toxicologic effects on embryo-fetal rats and rabbits.
If Biktarvy, Pifeltro, or Trogarzo are used in pregnancy, health care providers are encouraged to register the patient in the Antiretroviral Pregnancy Registry by calling 1-800-258-4263.
There are three new agents in the tetracycline class.
Nuzyra (omadacycline), which has a MW of about 729, is for community-acquired bacterial pneumonia and acute bacterial skin and skin structure infections.
Seysara (sarecycline), which has a MW of about 524, is for inflammatory lesions of nonnodular, moderate to severe acne vulgaris.
Xerava (eravacycline), which has a MW of about 632, is for complicated intra-abdominal infection.
The various dose-related toxicities observed with the three drugs in rats and rabbits included maternal deaths; increased postimplantation loss; reduced fetal body weights; delays in skeletal ossification; and fetal malformations of the skeleton, heart, and lung. Use of these drugs in the last half of pregnancy may cause permanent discoloration of the teeth and enamel hypoplasia, as well as inhibition of bone growth.
Antilipemic agents
Crysvita (burosumab-twza), which has a MW of about 147,000, is a fibroblast growth factor–blocking antibody indicated for the treatment of X-linked hypophosphatemia. In pregnant cynomolgus monkeys, doses slightly higher than the human dose were not teratogenic. The drug was detected in fetal serum indicating that it crossed the monkey placenta.
Tegsedi (inotersen), which has a MW of about 7,601, is an amyloidosis inhibitor used for polyneuropathy of hereditary transthyretin-mediated amyloidosis. It is available only through a restricted program. The drug was not teratogenic in mice and rabbits; however, it does decrease vitamin A levels, so supplementation with the vitamin is recommended.
Antineoplastics
The manufacturers recommend avoiding these drugs during pregnancy. Effective contraception should be used.
Daurismo (glasdegib), which has a MW of about 491, is a hedgehog pathway inhibitor indicated in combination with low-dose cytarabine for newly diagnosed acute myeloid leukemia (AML). The drug caused embryotoxicity, fetotoxicity, and teratogenicity in rats and rabbits at doses less than the human dose.
Erleada (apalutamide), which has a MW of about 477, is an androgen receptor inhibitor indicated for nonmetastatic, castration-resistant prostate cancer. Animal studies were not conducted because the drug should not be used in females.
Elzonris (tagraxofusp-erzs), which has a MW of 57,695, is a cytotoxin indicated for the treatment of blastic plasmacytoid dendritic cell neoplasm. Animal studies have not been conducted.
Lumoxiti (moxetumomab pasudotox–tdfk) which as a MW of about 63,000, is indicated for relapsed or refractory hairy cell leukemia. Studies have not been conducted in pregnant animals. Two life-threatening outcomes have occurred with the drug: capillary leak syndrome and hemolytic uremic syndrome. The drug should be discontinued if either occurs.
Lutathera (lutetium Lu 177 dotatate), which has a MW of about 1,610, is a radiolabeled somatostatin analogue given as a single intravenous dose every 8 weeks for four doses for the treatment of gastroenteropancreatic neuroendocrine tumors. Reproductive studies in animals have not been conducted. However, all radiopharmaceuticals have the potential to cause embryo-fetal harm. They also can cause infertility in males and females.
Talzenna (talazoparib), which has a MW of about 553, is a poly (ADP-ribose) polymerase inhibitor indicated for the treatment of certain types of breast cancer. At doses much less then the human dose, the drug caused fetal malformations and embryo-fetal death in rats.
Tibsovo (ivosidenib), which has a MW of 583, is an isocitrate dehydrogenase 1 inhibitor used for patients with relapsed or refractory AML. The drug caused embryo-fetal toxicity in rats and rabbits at doses slighter higher than the human dose.
There are seven new kinase inhibitors.
Braftovi (encorafenib), which has a MW of 540, is indicated in combination with Mektovi for patients with a specific type of metastatic melanoma. The drug caused embryo-fetal toxicity in rats and rabbits.
Copiktra (duvelisib), which has a MW of about 435, is indicated for treatment of chronic lymphocytic leukemia and follicular lymphoma. In rats and rabbits, the drug caused embryo-fetal death, lower fetal weights, and malformations.
Lorbrena (lorlatinib), which has a MW of about 406, is given for the treatment of metastatic non–small cell lung cancer. In rats and rabbits, the drug caused abortions, decreased fetal body weight, and major malformations.
Mektovi (binimetinib), which has a MW of about 441, is used in combination with Braftovi for patients with a specific type of melanoma. The drug was embryotoxic and abortifacient in rabbits.
Vitrakvi (larotrectinib), which has a MW of about 527, is used for patients with solid tumors. Studies in rats revealed fetal anasarca (extreme generalized edema) and omphalocele in rabbits.
Vizimpro (dacomitinib), which has a MW of about 488, is indicated for metastatic non–small cell lung cancer. The drug caused embryo-fetal toxicity in rats and mice.
Xospata (gilteritinib), which has a MW of about 1,222, is indicated for relapsed or refractory AML. In rats, the drug caused embryo-fetal death, suppressed fetal growth, and caused multiple malformations.
Three drugs are classified as monoclonal antibodies.
Gamifant (emapalumab), which has a MW of about 148,000, is indicated for primary hemophagocytic lymphohistiocytosis. A murine surrogate antimouse antibody was given to pregnant mice throughout gestation and no fetal harm was observed.
Libtayo (cemiplimab-rwlc), which has a MW of 146,000, is indicated for patients with metastatic or locally advanced cutaneous squamous cell carcinoma. Animal reproduction studies have not been conducted; however, based on its mechanism, increased rates of abortion or stillbirth may occur if the drug is used in human pregnancy.
Poteligeo (mogamulizumab-kpkc), which has a MW of about 149,000, is given for relapsed/refractory mycosis fungoides or Sézary syndrome. In pregnant monkeys, there was no embryo-fetal lethality, teratogenicity, fetal growth restriction, spontaneous abortion, or increased fetal death.
Central nervous system
There are three antimigraine agents that are monoclonal antibodies given as a subcutaneous injection.
Aimovig (erenumab-aooe), which has a MW of about 150,000, caused no adverse effects in monkey offspring.
Ajovy (fremanezumab-vfrm), which has a MW of about 148,000, had no adverse effect in rat and rabbit offspring.
Emgality (galcanezumab-gnlm), which has a MW of about 147,000, produced no adverse effects in rat and rabbit offspring.
Diacomit (stiripentol), which has a MW of about 234, is an anticonvulsant used to treat seizures associated with Dravet syndrome. The drug caused severe embryo-fetal toxicity in mice, rabbits, and rats. The drug is included in the North American Antiepileptic Drug (NAAED) Pregnancy Registry. Patients can enroll themselves by calling the toll-free number 1-888-233-2334 or visiting http://aedpregnancyregistry.org/.
Epidiolex (cannabidiol), which has a MW of about 314, is an anticonvulsant indicated for the treatment of seizures associated with Lennox-Gastaut syndrome or Dravet syndrome. In pregnant rats, doses up to about 16 times the recommended human dose (RHD) caused no embryo-fetal adverse effects. The drug caused decreased fetal body weights, increased fetal structural variations, and maternal toxicity when the drug was given to pregnant rabbits throughout organogenesis. The no-effect dose for embryo-fetal toxicity was less than the human dose. Patients can enroll themselves in the NAAED Pregnancy Registry by calling the toll-free number 1-888-233-2334 or visiting http://aedpregnancyregistry.org/.
Firdapse (amifampridine), a potassium channel blocker with a MW of about 201, is used for the treatment of Lambert-Eaton myasthenic syndrome. No adverse effects on embryo-fetal development were observed in rats and rabbits given the drug throughout organogenesis. However, in rats given the drug throughout pregnancy and lactation, there was an increase in stillbirths and pup deaths, reduced pup weight, and delayed sexual development in female pups.
Lucemyra (lofexidine), which has a MW of about 296, is used to mitigate opioid withdrawal symptoms to facilitate abrupt opioid discontinuation in adults. The drug caused severe toxicity in the fetuses of rats and rabbits.
Olumiant (baricitinib), which has a MW of about 371, is a Janus kinase inhibitor indicated for the treatment of rheumatoid arthritis. The drug was teratogenic in pregnant rats given doses about 20 times greater than the maximum RHD based on area under the curve. In rabbits, embryo death and rib anomalies were observed with doses 84 times greater than the maximum RHD, but no developmental toxicity was seen with doses 12 times greater than the maximum RHD.
Orilissa (elagolix), which has a MW of about 654, is a gonadotropin-releasing hormone receptor antagonist indicated for the management of pain associated with endometriosis. The drug caused abortions in rats and rabbits. Because the drug may increase the risk of early pregnancy loss, the manufacturer classifies it as contraindicated in pregnancy.
Dermatologic agents
Ilumya (tildrakizumab), which has a MW of about 147,000, is given by subcutaneous injection for the treatment of moderate to severe plaque psoriasis. When given during organogenesis in monkeys, no maternal or embryo-fetal toxicities were observed. However, when given throughout pregnancy a few neonatal deaths occurred, but the clinical significance of these nonclinical findings were unknown.
Fabry disease
Galafold (migalastat), which has a MW of about 200, is an alpha-galactosidase A pharmacologic chaperone indicated for the treatment of Fabry disease. Three pregnant women with Fabry disease were exposed to the drug in clinical studies but no information was provided on the pregnancy outcomes. No adverse developmental effects were observed in pregnant rats and rabbits.
Gastrointestinal agents
Akynzeo (netupitant or fosnetupitant palonosetron), which have MWs of about 579, 333, and 762, respectively, is available as an oral capsule (netupitant + palonosetron) and as an intravenous formulation (fosnetupitant + palonosetron). They are indicated, in combination with dexamethasone, for the prevention of nausea and vomiting related to cancer chemotherapy. Netupitant and fosnetupitant produced no embryo-fetal adverse effects in rats but were toxic to rabbit embryos. Palonosetron caused no embryo-fetal adverse effects in rats and rabbits.
Motegrity (prucalopride), which has a MW of about 486, is indicated for chronic idiopathic constipation. No adverse embryo-fetal developmental effects were observed in rats and rabbits.
Hematologic agents
Doptelet (avatrombopag), which has a MW of about 766, is indicated for the treatment of thrombocytopenia in adult patients with chronic liver disease who are scheduled to undergo a procedure. No embryo-fetal effects were observed in rats, but in rabbits the drug was associated with spontaneous abortions.
Lokelma (sodium zirconium cyclosilicate) is a nonabsorbed zirconium silicate that exchanges potassium for hydrogen and sodium. Animal studies have not been conducted. Because it is not absorbed, it is not expected to result in fetal exposure to the drug.
Mulpleta (lusutrombopag), which has a MW of about 592, a thrombopoietin receptor agonist, is indicated for the treatment of thrombocytopenia in patients with chronic liver disease. High levels of the drug in pregnant rats were associated with adverse developmental outcomes. No adverse embryo-fetal effects were seen in pregnant rabbits.
Palynziq (pegvaliase-pqpz), which has a MW of about 1,000,000, is a phenylalanine-metabolizing enzyme indicated to reduce blood phenylalanine concentrations in patients with phenylketonuria. In pregnant rats, the drug caused an increase in skeletal variations. In rabbits, the drug caused a high incidence of multiple malformations.
Takhzyro (lanadelumab-flyo), which has a MW of about 49,000, is a monoclonal antibody indicated for prophylaxis to prevent attacks of hereditary angioedema. The drug caused no fetal harm in monkeys.
Tavalisse (fostamatinib disodium hexahydrate), which has a MW of about 733, is a kinase inhibitor used for the treatment of thrombocytopenia. In pregnant rats and rabbits, the drug caused adverse developmental outcomes including embryo-fetal mortality, lower fetal weights, and structural anomalies.
Ultomiris (ravulizumab), which has a MW of about 148,000, is a humanized monoclonal antibody indicated for adult patients with paroxysmal nocturnal hemoglobinuria. In mice, the drug was associated with increased rates of developmental abnormalities and an increased rate of dead and moribund offspring.
Immunologic agent
Revcovi (elapegademase-lvlr), which has a MW of about 113,000, is a recombinant adenosine deaminase indicated for the treatment of adenosine deaminase severe combined immune deficiency. Animal studies in pregnancy have not been conducted.
Nutrient/Nutritional supplement
Fish oil is indicated as a source of calories and fatty acids in pediatric patients with parenteral nutrition-associated cholestasis. Animal reproduction studies have not been conducted. It is doubtful if this product will be used in pregnancy.
Ophthalmic – nerve growth factor
Oxervate (cenegermin-bkbj), which has a MW of 13,266, is a solution that contains 118 amino acids. It is a recombinant human nerve growth factor indicated for neurotrophic keratitis. In rats and rabbits given the drug during organogenesis, there was a slight increase in postimplantation loss at doses greater than or equal to 267 times the human dose.
Respiratory drugs
Symdeko (tezacaftor + ivacaftor), which have MWs of about 521 and 392, is indicated for the treatment of patients with cystic fibrosis who are homozygous for the F508del mutation or who have at least one mutation in the cystic fibrosis transmembrane conductance regulator gene. There were no adverse developmental effects in pregnant rats and rabbits when the drugs were used separately or combined.
Yupelri (revefenacin), which has a MW of about 598, is an anticholinergic drug. It is an inhaled solution for the maintenance treatment of chronic obstructive pulmonary disease. In rats and rabbits, doses that were about 209 times the RHD produced no evidence of fetal harm.
Mr. Briggs is clinical professor of pharmacy at the University of California, San Francisco, and adjunct professor of pharmacy at the University of Southern California, Los Angeles, as well as at Washington State University, Spokane. Mr. Briggs reported no relevant financial disclosures. Email him at obnews@mdedge.com.
Postpartum hypertension
When managing our pregnant patients, we often might be tempted to view the delivery of the baby as the conclusion of prenatal care. For many women, the baby’s birth coincides with a resolution of health conditions that they may have experienced during pregnancy, including edema, gestational diabetes, and hypertensive disorders. However, the postpartum period remains a critical time in the health of the mother. Indeed, the weeks immediately following parturition often are colloquially referred to as the fourth trimester, further emphasizing the importance of appropriate patient management and care during this time.
One of the key health conditions we must monitor in the immediate postpartum period is hypertension. According to a 2018 report compiling data from nine of the Centers for Disease Control and Prevention’s Maternal Mortality Review Committees, hypertensive disorders accounted for approximately 9.3% of pregnancy-related maternal deaths within 42 days after delivery (http://reviewtoaction.org/Report_from_Nine_MMRCs). Although women who have hypertensive disorders during pregnancy are at risk for complications after giving birth, women without gestational hypertension, preeclampsia, or eclampsia can experience these conditions post partum at a rate between 0.3% and 27.5% (Am J Obstet Gynecol 2012 Jun;206[6]:470-5). Therefore, we cannot assume that a patient with an uncomplicated pregnancy is completely “in the clear” after delivery.
Despite these somewhat grim statistics, With vigilant monitoring and strong communication with our patients, ob.gyns. can reduce the risks of these complications from occurring, more quickly resolve symptoms as they might arise, and significantly improve the health and well-being of new mothers in the fourth trimester.
The importance of caring for all of our patients along the continuum of pregnancy, especially as it pertains to monitoring and preventing postpartum hypertension, is the focus of the third and final installment of this Master Class series on hypertension in pregnancy authored by Dr. Baha Sibai, professor of obstetrics, gynecology, and reproductive sciences at the University of Texas McGovern Medical School, Houston.
Dr. Reece, who specializes in maternal-fetal medicine, is executive vice president for medical affairs at the University of Maryland, Baltimore, as well as the John Z. and Akiko K. Bowers Distinguished Professor and dean of the school of medicine. He is the medical editor of this column. He said he had no relevant financial disclosures. Contact him at obnews@mdedge.com.
When managing our pregnant patients, we often might be tempted to view the delivery of the baby as the conclusion of prenatal care. For many women, the baby’s birth coincides with a resolution of health conditions that they may have experienced during pregnancy, including edema, gestational diabetes, and hypertensive disorders. However, the postpartum period remains a critical time in the health of the mother. Indeed, the weeks immediately following parturition often are colloquially referred to as the fourth trimester, further emphasizing the importance of appropriate patient management and care during this time.
One of the key health conditions we must monitor in the immediate postpartum period is hypertension. According to a 2018 report compiling data from nine of the Centers for Disease Control and Prevention’s Maternal Mortality Review Committees, hypertensive disorders accounted for approximately 9.3% of pregnancy-related maternal deaths within 42 days after delivery (http://reviewtoaction.org/Report_from_Nine_MMRCs). Although women who have hypertensive disorders during pregnancy are at risk for complications after giving birth, women without gestational hypertension, preeclampsia, or eclampsia can experience these conditions post partum at a rate between 0.3% and 27.5% (Am J Obstet Gynecol 2012 Jun;206[6]:470-5). Therefore, we cannot assume that a patient with an uncomplicated pregnancy is completely “in the clear” after delivery.
Despite these somewhat grim statistics, With vigilant monitoring and strong communication with our patients, ob.gyns. can reduce the risks of these complications from occurring, more quickly resolve symptoms as they might arise, and significantly improve the health and well-being of new mothers in the fourth trimester.
The importance of caring for all of our patients along the continuum of pregnancy, especially as it pertains to monitoring and preventing postpartum hypertension, is the focus of the third and final installment of this Master Class series on hypertension in pregnancy authored by Dr. Baha Sibai, professor of obstetrics, gynecology, and reproductive sciences at the University of Texas McGovern Medical School, Houston.
Dr. Reece, who specializes in maternal-fetal medicine, is executive vice president for medical affairs at the University of Maryland, Baltimore, as well as the John Z. and Akiko K. Bowers Distinguished Professor and dean of the school of medicine. He is the medical editor of this column. He said he had no relevant financial disclosures. Contact him at obnews@mdedge.com.
When managing our pregnant patients, we often might be tempted to view the delivery of the baby as the conclusion of prenatal care. For many women, the baby’s birth coincides with a resolution of health conditions that they may have experienced during pregnancy, including edema, gestational diabetes, and hypertensive disorders. However, the postpartum period remains a critical time in the health of the mother. Indeed, the weeks immediately following parturition often are colloquially referred to as the fourth trimester, further emphasizing the importance of appropriate patient management and care during this time.
One of the key health conditions we must monitor in the immediate postpartum period is hypertension. According to a 2018 report compiling data from nine of the Centers for Disease Control and Prevention’s Maternal Mortality Review Committees, hypertensive disorders accounted for approximately 9.3% of pregnancy-related maternal deaths within 42 days after delivery (http://reviewtoaction.org/Report_from_Nine_MMRCs). Although women who have hypertensive disorders during pregnancy are at risk for complications after giving birth, women without gestational hypertension, preeclampsia, or eclampsia can experience these conditions post partum at a rate between 0.3% and 27.5% (Am J Obstet Gynecol 2012 Jun;206[6]:470-5). Therefore, we cannot assume that a patient with an uncomplicated pregnancy is completely “in the clear” after delivery.
Despite these somewhat grim statistics, With vigilant monitoring and strong communication with our patients, ob.gyns. can reduce the risks of these complications from occurring, more quickly resolve symptoms as they might arise, and significantly improve the health and well-being of new mothers in the fourth trimester.
The importance of caring for all of our patients along the continuum of pregnancy, especially as it pertains to monitoring and preventing postpartum hypertension, is the focus of the third and final installment of this Master Class series on hypertension in pregnancy authored by Dr. Baha Sibai, professor of obstetrics, gynecology, and reproductive sciences at the University of Texas McGovern Medical School, Houston.
Dr. Reece, who specializes in maternal-fetal medicine, is executive vice president for medical affairs at the University of Maryland, Baltimore, as well as the John Z. and Akiko K. Bowers Distinguished Professor and dean of the school of medicine. He is the medical editor of this column. He said he had no relevant financial disclosures. Contact him at obnews@mdedge.com.
Recognition, evaluation, and management of postpartum hypertension
Postpartum hypertension has a host of potential causes, some of which may be benign (such as the persistence of mild gestational hypertension or mild chronic hypertension) whereas others (such as severe de novo preeclampsia-eclampsia and HELLP syndrome [a complication of pregnancy characterized by hemolysis, elevated liver enzymes, and a low platelet count]) can be life threatening.
Postpartum hypertension may occur secondary to lupus, hyperthyroidism, hemolytic uremic syndrome, stroke, and other conditions, which means that we must have a high index of suspicion for secondary dangerous causes of hypertension when evaluating such women.
With monitoring, reporting, and prompt evaluation of symptoms in the postpartum period – and with patient education on signs and symptoms of severe hypertension and preeclampsia (PE) – we can expect to avoid a range of potential maternal complications, from hypertensive encephalopathy, liver hemorrhage, renal failure, and the development of eclampsia, ischemic stroke/cerebral hemorrhage, pulmonary edema, and cardiomyopathy.
Most women with gestational hypertension (GHTN) become normotensive during the first week post partum, but in women who develop PE during pregnancy, hypertension often takes longer to resolve. Some of these women may have an initial decrease in blood pressure immediately post partum followed by development of hypertension again between days 3 and 6. Therefore, This can be achieved either in-hospital, through home BP monitoring, or with in-office visits.
In addition, all women – including those who did not have hypertension during their pregnancies – should be educated about the signs and symptoms of severe hypertension or PE and instructed to report these to a medical provider in a timely fashion. Severe hypertension or PE with severe features may develop for the first time during the postpartum period either before or after hospital discharge. It is important to appreciate, moreover, that approximately 25%-40% of cases of eclampsia develop in the postpartum period with onset ranging from 2 days to 6 weeks after delivery. Moreover, almost one-third of women who develop the HELLP syndrome do so during the postpartum period.
Management of persistent hypertension
The most common causes for persistent hypertension beyond 48 hours after delivery are GHTN, PE, or chronic hypertension. Initial management will depend on history, clinical findings, presence or absence of associated symptoms, results of laboratory findings (urine protein, platelet count, liver enzymes, serum creatinine, and electrolytes), and response to prior treatment of hypertension.
Certain medications that frequently are prescribed in the postpartum period, such as ergonovine and decongestants, should be discontinued if they are being used. These agents can aggravate preexisting hypertension or result in new-onset hypertension if used in large or frequent doses. Their use also may be associated with cerebral symptoms, nausea, and vomiting.
Subsequent management includes close observation until resolution of hypertension and associated symptoms. If the patient has hypertension only with no symptoms, no proteinuria, and normal laboratory findings, BP control is the focus; antihypertensives are used if systolic BP remains persistently greater than or equal to 150 mm Hg and/or if diastolic BP persists at greater than or equal to 100 mm Hg. Intravenous boluses of either labetalol or hydralazine or oral rapid-acting nifedipine are used initially if systolic BP is greater than or equal to 160 mm Hg or diastolic BP greater than or equal to 110 mm Hg persists for at least 30 minutes. This is followed by oral medication to keep systolic BP less than 150 mg Hg and diastolic BP less than 100 mm Hg.
For patients with persistent hypertension after GHTN or PE, I recommend oral long-acting nifedipine XL (30 mg every 12 hours) or oral labetalol (200 mg every 8-12 hours). Compared with labetalol, oral nifedipine is associated with improved renal blood flow with resultant diuresis, which makes it the drug of choice in women with volume overload. In some, it is necessary to switch to a new agent such as an angiotensin-converting enzyme (ACE) inhibitor; an ACE inhibitor is the drug of choice in those with pregestational diabetes mellitus, renal disease, or cardiomyopathy. In addition, thiazide or loop diuretics may be needed in women with circulatory overload and in those with pulmonary edema. Antihypertensives such as nifedipine, labetalol, furosemide, captopril, and enalapril are compatible with breastfeeding.
If the BP remains less than 150 mm Hg (systolic) and/or less than 100 mm Hg (diastolic) for 24 hours, and there are no maternal symptoms, the patient may be discharged home with instructions for daily BP measurements (self or by a visiting nurse) and the reporting of symptoms until her next visit in 1 week. Antihypertensives then are discontinued if the BP remains below the hypertensive levels for at least 48 hours. This may take 1 or several weeks to achieve.
Women with PE with severe features should receive close monitoring of BP and of symptoms during the immediate postpartum period, as well as accurate measurements of fluid intake, urinary output, and weight gain. These women often have received large amounts of IV fluids during labor as a result of prehydration before epidural analgesia, as well as IV fluids administered during the use of oxytocin and magnesium sulfate in labor and post partum. Mobilization of extracellular fluid also leads to increased intravascular volume. As a result, women who have PE with severe features – particularly those with abnormal renal function, capillary leak, or early-onset disease – are at increased risk for pulmonary edema and exacerbation of severe hypertension.
Careful evaluation of the volume of IV fluids, oral intake, blood products, urine output, respiratory symptoms, and vital signs is advised. Patients who develop tachycardia or respiratory symptoms such as dry cough, shortness of breath, or orthopnea also should be monitored with pulse oximetry and frequent chest auscultation, as well as chest x-ray.
New-onset severe symptoms
Because severe hypertension or PE with severe features may develop for the first time during the postpartum period, postpartum women – and the medical providers and personnel who respond to patient phone calls – should be well educated about the signs and symptoms of severe hypertension or PE. These include new-onset severe headaches that do not respond to maximum doses of analgesics, persistent severe visual changes, and new-onset epigastric pain with nausea and vomiting, dyspnea, orthopnea, shortness of breath, or palpitations. These women are at increased risk for eclampsia, pulmonary edema, stroke, and thromboembolism; these women require careful evaluation and potential hospitalization.
Severe new onset of persistent headaches and/or visual symptoms. Women with hypertension in association with new-onset persistent headaches and/or visual changes should be suspected to have severe PE. Patients who have hypertension with seizure should be initially treated as having eclampsia and should receive brain imaging to rule out other etiologies. Magnesium sulfate therapy must be initiated promptly for seizure prophylaxis and/or treatment. In addition, intravenous antihypertensive medications are recommended to lower BP to the desired goal while considering an alternative cause for the cerebral symptoms.
Women presenting with hypertension in association with refractory and/or thunderclap headaches, visual disturbances, or neurologic deficits should be evaluated for possible cerebrovascular complications such as reversible cerebral vasoconstriction syndrome (RCVS), cerebral venous thrombosis, or stroke. These women will require selective diagnostic neuroimaging and consultation with neurology and/or neurosurgery. Such an evaluation may include CT scan for hemorrhage, MRI for detection of vasogenic edema and/or ischemia or infarction, cerebral angiography for diagnosis of RCVS, and cerebral venography for detection of cerebral venous thrombosis. Subsequent treatment will depend on the etiology.
Severe new-onset epigastric/right upper quadrant pain with nausea and vomiting. Women with persistent nausea, vomiting, or epigastric pain should be evaluated for HELLP syndrome because up to 30% who develop the syndrome do so post partum. The time of onset of clinical and laboratory findings ranges from 1 to 7 days post partum. Women are managed as they are before delivery, with the use of magnesium sulfate, antihypertensives, and close monitoring of vital signs and laboratory values.
In general, patients with HELLP syndrome will demonstrate an improvement in clinical and laboratory findings within 72 hours after treatment. If there is either no improvement or a deterioration in these findings, then it is important to consult with appropriate specialists for evaluation and subsequent management of possible rare syndromes such as acute fatty liver, thrombotic thrombocytopenic purpura, hemolytic uremic syndrome, or exacerbation of lupus.
Severe new-onset shortness of breath, dyspnea, orthopnea, or palpitations. Women with these symptoms in the postpartum period should be evaluated for possible pulmonary edema, pulmonary embolism, or peripartum cardiomyopathy. Women with postpartum hypertension are at risk for pulmonary edema with onset at 3-6 days after delivery. Diagnosis is confirmed by physical exam (tachycardia, tachypnea), presence of rales on lung exam, pulse oximetry (oxygen saturation less than 93%), and chest x-ray, and echocardiography to exclude other etiologies. Treatment of pulmonary edema includes oxygen supplementation, 40 mg IV furosemide, control of severe hypertension, fluid restriction, and supportive care.
Pulmonary embolism usually is confirmed by chest CT angiography and managed with therapeutic anticoagulation. Peripartum cardiomyopathy is diagnosed by echocardiography revealing left ventricular systolic dysfunction (ejection fraction less than 45%, dilated left ventricle). Treatment includes IV furosemide, use of a vasodilator, and ACE inhibitor therapy.
Remote prognosis
Recent research suggests that women who develop PE may be at increased risk for future cardiovascular disease such as heart failure, coronary artery disease, and stroke later in life. Indeed, many of the risk factors and pathophysiologic abnormalities of PE are similar to those of coronary artery disease.
The American College of Obstetricians and Gynecologists and the American Heart Association recommend that women with PE receive close observation in the postpartum period and careful evaluation in the first year after delivery to identify those who could benefit from early intervention to prevent subsequent cardiovascular disease. In general, when pregnancies are complicated by PE, there are opportunities for lifestyle and risk factor modification.
Dr. Sibai is professor of obstetrics, gynecology, and reproductive sciences at the University of Texas McGovern Medical School, Houston
Postpartum hypertension has a host of potential causes, some of which may be benign (such as the persistence of mild gestational hypertension or mild chronic hypertension) whereas others (such as severe de novo preeclampsia-eclampsia and HELLP syndrome [a complication of pregnancy characterized by hemolysis, elevated liver enzymes, and a low platelet count]) can be life threatening.
Postpartum hypertension may occur secondary to lupus, hyperthyroidism, hemolytic uremic syndrome, stroke, and other conditions, which means that we must have a high index of suspicion for secondary dangerous causes of hypertension when evaluating such women.
With monitoring, reporting, and prompt evaluation of symptoms in the postpartum period – and with patient education on signs and symptoms of severe hypertension and preeclampsia (PE) – we can expect to avoid a range of potential maternal complications, from hypertensive encephalopathy, liver hemorrhage, renal failure, and the development of eclampsia, ischemic stroke/cerebral hemorrhage, pulmonary edema, and cardiomyopathy.
Most women with gestational hypertension (GHTN) become normotensive during the first week post partum, but in women who develop PE during pregnancy, hypertension often takes longer to resolve. Some of these women may have an initial decrease in blood pressure immediately post partum followed by development of hypertension again between days 3 and 6. Therefore, This can be achieved either in-hospital, through home BP monitoring, or with in-office visits.
In addition, all women – including those who did not have hypertension during their pregnancies – should be educated about the signs and symptoms of severe hypertension or PE and instructed to report these to a medical provider in a timely fashion. Severe hypertension or PE with severe features may develop for the first time during the postpartum period either before or after hospital discharge. It is important to appreciate, moreover, that approximately 25%-40% of cases of eclampsia develop in the postpartum period with onset ranging from 2 days to 6 weeks after delivery. Moreover, almost one-third of women who develop the HELLP syndrome do so during the postpartum period.
Management of persistent hypertension
The most common causes for persistent hypertension beyond 48 hours after delivery are GHTN, PE, or chronic hypertension. Initial management will depend on history, clinical findings, presence or absence of associated symptoms, results of laboratory findings (urine protein, platelet count, liver enzymes, serum creatinine, and electrolytes), and response to prior treatment of hypertension.
Certain medications that frequently are prescribed in the postpartum period, such as ergonovine and decongestants, should be discontinued if they are being used. These agents can aggravate preexisting hypertension or result in new-onset hypertension if used in large or frequent doses. Their use also may be associated with cerebral symptoms, nausea, and vomiting.
Subsequent management includes close observation until resolution of hypertension and associated symptoms. If the patient has hypertension only with no symptoms, no proteinuria, and normal laboratory findings, BP control is the focus; antihypertensives are used if systolic BP remains persistently greater than or equal to 150 mm Hg and/or if diastolic BP persists at greater than or equal to 100 mm Hg. Intravenous boluses of either labetalol or hydralazine or oral rapid-acting nifedipine are used initially if systolic BP is greater than or equal to 160 mm Hg or diastolic BP greater than or equal to 110 mm Hg persists for at least 30 minutes. This is followed by oral medication to keep systolic BP less than 150 mg Hg and diastolic BP less than 100 mm Hg.
For patients with persistent hypertension after GHTN or PE, I recommend oral long-acting nifedipine XL (30 mg every 12 hours) or oral labetalol (200 mg every 8-12 hours). Compared with labetalol, oral nifedipine is associated with improved renal blood flow with resultant diuresis, which makes it the drug of choice in women with volume overload. In some, it is necessary to switch to a new agent such as an angiotensin-converting enzyme (ACE) inhibitor; an ACE inhibitor is the drug of choice in those with pregestational diabetes mellitus, renal disease, or cardiomyopathy. In addition, thiazide or loop diuretics may be needed in women with circulatory overload and in those with pulmonary edema. Antihypertensives such as nifedipine, labetalol, furosemide, captopril, and enalapril are compatible with breastfeeding.
If the BP remains less than 150 mm Hg (systolic) and/or less than 100 mm Hg (diastolic) for 24 hours, and there are no maternal symptoms, the patient may be discharged home with instructions for daily BP measurements (self or by a visiting nurse) and the reporting of symptoms until her next visit in 1 week. Antihypertensives then are discontinued if the BP remains below the hypertensive levels for at least 48 hours. This may take 1 or several weeks to achieve.
Women with PE with severe features should receive close monitoring of BP and of symptoms during the immediate postpartum period, as well as accurate measurements of fluid intake, urinary output, and weight gain. These women often have received large amounts of IV fluids during labor as a result of prehydration before epidural analgesia, as well as IV fluids administered during the use of oxytocin and magnesium sulfate in labor and post partum. Mobilization of extracellular fluid also leads to increased intravascular volume. As a result, women who have PE with severe features – particularly those with abnormal renal function, capillary leak, or early-onset disease – are at increased risk for pulmonary edema and exacerbation of severe hypertension.
Careful evaluation of the volume of IV fluids, oral intake, blood products, urine output, respiratory symptoms, and vital signs is advised. Patients who develop tachycardia or respiratory symptoms such as dry cough, shortness of breath, or orthopnea also should be monitored with pulse oximetry and frequent chest auscultation, as well as chest x-ray.
New-onset severe symptoms
Because severe hypertension or PE with severe features may develop for the first time during the postpartum period, postpartum women – and the medical providers and personnel who respond to patient phone calls – should be well educated about the signs and symptoms of severe hypertension or PE. These include new-onset severe headaches that do not respond to maximum doses of analgesics, persistent severe visual changes, and new-onset epigastric pain with nausea and vomiting, dyspnea, orthopnea, shortness of breath, or palpitations. These women are at increased risk for eclampsia, pulmonary edema, stroke, and thromboembolism; these women require careful evaluation and potential hospitalization.
Severe new onset of persistent headaches and/or visual symptoms. Women with hypertension in association with new-onset persistent headaches and/or visual changes should be suspected to have severe PE. Patients who have hypertension with seizure should be initially treated as having eclampsia and should receive brain imaging to rule out other etiologies. Magnesium sulfate therapy must be initiated promptly for seizure prophylaxis and/or treatment. In addition, intravenous antihypertensive medications are recommended to lower BP to the desired goal while considering an alternative cause for the cerebral symptoms.
Women presenting with hypertension in association with refractory and/or thunderclap headaches, visual disturbances, or neurologic deficits should be evaluated for possible cerebrovascular complications such as reversible cerebral vasoconstriction syndrome (RCVS), cerebral venous thrombosis, or stroke. These women will require selective diagnostic neuroimaging and consultation with neurology and/or neurosurgery. Such an evaluation may include CT scan for hemorrhage, MRI for detection of vasogenic edema and/or ischemia or infarction, cerebral angiography for diagnosis of RCVS, and cerebral venography for detection of cerebral venous thrombosis. Subsequent treatment will depend on the etiology.
Severe new-onset epigastric/right upper quadrant pain with nausea and vomiting. Women with persistent nausea, vomiting, or epigastric pain should be evaluated for HELLP syndrome because up to 30% who develop the syndrome do so post partum. The time of onset of clinical and laboratory findings ranges from 1 to 7 days post partum. Women are managed as they are before delivery, with the use of magnesium sulfate, antihypertensives, and close monitoring of vital signs and laboratory values.
In general, patients with HELLP syndrome will demonstrate an improvement in clinical and laboratory findings within 72 hours after treatment. If there is either no improvement or a deterioration in these findings, then it is important to consult with appropriate specialists for evaluation and subsequent management of possible rare syndromes such as acute fatty liver, thrombotic thrombocytopenic purpura, hemolytic uremic syndrome, or exacerbation of lupus.
Severe new-onset shortness of breath, dyspnea, orthopnea, or palpitations. Women with these symptoms in the postpartum period should be evaluated for possible pulmonary edema, pulmonary embolism, or peripartum cardiomyopathy. Women with postpartum hypertension are at risk for pulmonary edema with onset at 3-6 days after delivery. Diagnosis is confirmed by physical exam (tachycardia, tachypnea), presence of rales on lung exam, pulse oximetry (oxygen saturation less than 93%), and chest x-ray, and echocardiography to exclude other etiologies. Treatment of pulmonary edema includes oxygen supplementation, 40 mg IV furosemide, control of severe hypertension, fluid restriction, and supportive care.
Pulmonary embolism usually is confirmed by chest CT angiography and managed with therapeutic anticoagulation. Peripartum cardiomyopathy is diagnosed by echocardiography revealing left ventricular systolic dysfunction (ejection fraction less than 45%, dilated left ventricle). Treatment includes IV furosemide, use of a vasodilator, and ACE inhibitor therapy.
Remote prognosis
Recent research suggests that women who develop PE may be at increased risk for future cardiovascular disease such as heart failure, coronary artery disease, and stroke later in life. Indeed, many of the risk factors and pathophysiologic abnormalities of PE are similar to those of coronary artery disease.
The American College of Obstetricians and Gynecologists and the American Heart Association recommend that women with PE receive close observation in the postpartum period and careful evaluation in the first year after delivery to identify those who could benefit from early intervention to prevent subsequent cardiovascular disease. In general, when pregnancies are complicated by PE, there are opportunities for lifestyle and risk factor modification.
Dr. Sibai is professor of obstetrics, gynecology, and reproductive sciences at the University of Texas McGovern Medical School, Houston
Postpartum hypertension has a host of potential causes, some of which may be benign (such as the persistence of mild gestational hypertension or mild chronic hypertension) whereas others (such as severe de novo preeclampsia-eclampsia and HELLP syndrome [a complication of pregnancy characterized by hemolysis, elevated liver enzymes, and a low platelet count]) can be life threatening.
Postpartum hypertension may occur secondary to lupus, hyperthyroidism, hemolytic uremic syndrome, stroke, and other conditions, which means that we must have a high index of suspicion for secondary dangerous causes of hypertension when evaluating such women.
With monitoring, reporting, and prompt evaluation of symptoms in the postpartum period – and with patient education on signs and symptoms of severe hypertension and preeclampsia (PE) – we can expect to avoid a range of potential maternal complications, from hypertensive encephalopathy, liver hemorrhage, renal failure, and the development of eclampsia, ischemic stroke/cerebral hemorrhage, pulmonary edema, and cardiomyopathy.
Most women with gestational hypertension (GHTN) become normotensive during the first week post partum, but in women who develop PE during pregnancy, hypertension often takes longer to resolve. Some of these women may have an initial decrease in blood pressure immediately post partum followed by development of hypertension again between days 3 and 6. Therefore, This can be achieved either in-hospital, through home BP monitoring, or with in-office visits.
In addition, all women – including those who did not have hypertension during their pregnancies – should be educated about the signs and symptoms of severe hypertension or PE and instructed to report these to a medical provider in a timely fashion. Severe hypertension or PE with severe features may develop for the first time during the postpartum period either before or after hospital discharge. It is important to appreciate, moreover, that approximately 25%-40% of cases of eclampsia develop in the postpartum period with onset ranging from 2 days to 6 weeks after delivery. Moreover, almost one-third of women who develop the HELLP syndrome do so during the postpartum period.
Management of persistent hypertension
The most common causes for persistent hypertension beyond 48 hours after delivery are GHTN, PE, or chronic hypertension. Initial management will depend on history, clinical findings, presence or absence of associated symptoms, results of laboratory findings (urine protein, platelet count, liver enzymes, serum creatinine, and electrolytes), and response to prior treatment of hypertension.
Certain medications that frequently are prescribed in the postpartum period, such as ergonovine and decongestants, should be discontinued if they are being used. These agents can aggravate preexisting hypertension or result in new-onset hypertension if used in large or frequent doses. Their use also may be associated with cerebral symptoms, nausea, and vomiting.
Subsequent management includes close observation until resolution of hypertension and associated symptoms. If the patient has hypertension only with no symptoms, no proteinuria, and normal laboratory findings, BP control is the focus; antihypertensives are used if systolic BP remains persistently greater than or equal to 150 mm Hg and/or if diastolic BP persists at greater than or equal to 100 mm Hg. Intravenous boluses of either labetalol or hydralazine or oral rapid-acting nifedipine are used initially if systolic BP is greater than or equal to 160 mm Hg or diastolic BP greater than or equal to 110 mm Hg persists for at least 30 minutes. This is followed by oral medication to keep systolic BP less than 150 mg Hg and diastolic BP less than 100 mm Hg.
For patients with persistent hypertension after GHTN or PE, I recommend oral long-acting nifedipine XL (30 mg every 12 hours) or oral labetalol (200 mg every 8-12 hours). Compared with labetalol, oral nifedipine is associated with improved renal blood flow with resultant diuresis, which makes it the drug of choice in women with volume overload. In some, it is necessary to switch to a new agent such as an angiotensin-converting enzyme (ACE) inhibitor; an ACE inhibitor is the drug of choice in those with pregestational diabetes mellitus, renal disease, or cardiomyopathy. In addition, thiazide or loop diuretics may be needed in women with circulatory overload and in those with pulmonary edema. Antihypertensives such as nifedipine, labetalol, furosemide, captopril, and enalapril are compatible with breastfeeding.
If the BP remains less than 150 mm Hg (systolic) and/or less than 100 mm Hg (diastolic) for 24 hours, and there are no maternal symptoms, the patient may be discharged home with instructions for daily BP measurements (self or by a visiting nurse) and the reporting of symptoms until her next visit in 1 week. Antihypertensives then are discontinued if the BP remains below the hypertensive levels for at least 48 hours. This may take 1 or several weeks to achieve.
Women with PE with severe features should receive close monitoring of BP and of symptoms during the immediate postpartum period, as well as accurate measurements of fluid intake, urinary output, and weight gain. These women often have received large amounts of IV fluids during labor as a result of prehydration before epidural analgesia, as well as IV fluids administered during the use of oxytocin and magnesium sulfate in labor and post partum. Mobilization of extracellular fluid also leads to increased intravascular volume. As a result, women who have PE with severe features – particularly those with abnormal renal function, capillary leak, or early-onset disease – are at increased risk for pulmonary edema and exacerbation of severe hypertension.
Careful evaluation of the volume of IV fluids, oral intake, blood products, urine output, respiratory symptoms, and vital signs is advised. Patients who develop tachycardia or respiratory symptoms such as dry cough, shortness of breath, or orthopnea also should be monitored with pulse oximetry and frequent chest auscultation, as well as chest x-ray.
New-onset severe symptoms
Because severe hypertension or PE with severe features may develop for the first time during the postpartum period, postpartum women – and the medical providers and personnel who respond to patient phone calls – should be well educated about the signs and symptoms of severe hypertension or PE. These include new-onset severe headaches that do not respond to maximum doses of analgesics, persistent severe visual changes, and new-onset epigastric pain with nausea and vomiting, dyspnea, orthopnea, shortness of breath, or palpitations. These women are at increased risk for eclampsia, pulmonary edema, stroke, and thromboembolism; these women require careful evaluation and potential hospitalization.
Severe new onset of persistent headaches and/or visual symptoms. Women with hypertension in association with new-onset persistent headaches and/or visual changes should be suspected to have severe PE. Patients who have hypertension with seizure should be initially treated as having eclampsia and should receive brain imaging to rule out other etiologies. Magnesium sulfate therapy must be initiated promptly for seizure prophylaxis and/or treatment. In addition, intravenous antihypertensive medications are recommended to lower BP to the desired goal while considering an alternative cause for the cerebral symptoms.
Women presenting with hypertension in association with refractory and/or thunderclap headaches, visual disturbances, or neurologic deficits should be evaluated for possible cerebrovascular complications such as reversible cerebral vasoconstriction syndrome (RCVS), cerebral venous thrombosis, or stroke. These women will require selective diagnostic neuroimaging and consultation with neurology and/or neurosurgery. Such an evaluation may include CT scan for hemorrhage, MRI for detection of vasogenic edema and/or ischemia or infarction, cerebral angiography for diagnosis of RCVS, and cerebral venography for detection of cerebral venous thrombosis. Subsequent treatment will depend on the etiology.
Severe new-onset epigastric/right upper quadrant pain with nausea and vomiting. Women with persistent nausea, vomiting, or epigastric pain should be evaluated for HELLP syndrome because up to 30% who develop the syndrome do so post partum. The time of onset of clinical and laboratory findings ranges from 1 to 7 days post partum. Women are managed as they are before delivery, with the use of magnesium sulfate, antihypertensives, and close monitoring of vital signs and laboratory values.
In general, patients with HELLP syndrome will demonstrate an improvement in clinical and laboratory findings within 72 hours after treatment. If there is either no improvement or a deterioration in these findings, then it is important to consult with appropriate specialists for evaluation and subsequent management of possible rare syndromes such as acute fatty liver, thrombotic thrombocytopenic purpura, hemolytic uremic syndrome, or exacerbation of lupus.
Severe new-onset shortness of breath, dyspnea, orthopnea, or palpitations. Women with these symptoms in the postpartum period should be evaluated for possible pulmonary edema, pulmonary embolism, or peripartum cardiomyopathy. Women with postpartum hypertension are at risk for pulmonary edema with onset at 3-6 days after delivery. Diagnosis is confirmed by physical exam (tachycardia, tachypnea), presence of rales on lung exam, pulse oximetry (oxygen saturation less than 93%), and chest x-ray, and echocardiography to exclude other etiologies. Treatment of pulmonary edema includes oxygen supplementation, 40 mg IV furosemide, control of severe hypertension, fluid restriction, and supportive care.
Pulmonary embolism usually is confirmed by chest CT angiography and managed with therapeutic anticoagulation. Peripartum cardiomyopathy is diagnosed by echocardiography revealing left ventricular systolic dysfunction (ejection fraction less than 45%, dilated left ventricle). Treatment includes IV furosemide, use of a vasodilator, and ACE inhibitor therapy.
Remote prognosis
Recent research suggests that women who develop PE may be at increased risk for future cardiovascular disease such as heart failure, coronary artery disease, and stroke later in life. Indeed, many of the risk factors and pathophysiologic abnormalities of PE are similar to those of coronary artery disease.
The American College of Obstetricians and Gynecologists and the American Heart Association recommend that women with PE receive close observation in the postpartum period and careful evaluation in the first year after delivery to identify those who could benefit from early intervention to prevent subsequent cardiovascular disease. In general, when pregnancies are complicated by PE, there are opportunities for lifestyle and risk factor modification.
Dr. Sibai is professor of obstetrics, gynecology, and reproductive sciences at the University of Texas McGovern Medical School, Houston
Depression: a changing concept in the age of ketamine
What does it mean to define an amalgamation of symptoms as a “psychiatric disorder?” Are psychiatric disorders an extreme variation of normative human behavior? Is human behavior simply an output phenotype of some neurologic chemical processes that become disordered in mental illness? Can depression be localized in the brain and subsequently turned on or off? If depression were to be localized in the brain, would it be an excess of a neurotransmitter, the depletion of a receptor, a malfunctioning neuron, an overactive connectome, poorly processed genetic material, or something as yet undefined? Those questions always have been present in our minds and influenced our understanding of patients, but a recent development in psychiatry raises questions about one of the few things we were historically confident about.
A part of our foundational understanding of depression was that it is not sadness, per se. One can be sad for any amount of time. It is not uncommon to feel sad for any variety of reasons, such as watching an adorable 60-second commercial for dog food.1 Those fleeting moments of sadness can even be empowering; they remind us about the things we care about and would be sad to miss.
Sadness in oneself can demonstrate the experience of empathic sadness for others. On the contrary, depression appears to have little apparent purpose, and instead results in a maladaptive way of coping that is all-consuming and often very damaging. Depression is not a mood but a state of being, something that is not defined by how one feels but who one is or has become because of the disorder. So it comes as somewhat of a surprise when we heard that ketamine could alleviate depression in minutes.2,3 As described by a ketamine expert, symptoms are relieved in “no less than an hour.”4 The surprise is not so much that a treatment would work but that improvement could be defined in such a short time frame.
Psychiatry has debated the definition of depression for its entire existence. There are many ways to tackle the concept of depression. A lot of the debate has been about the causes of depression. One example of the continued evolution of our understanding of depression is our prior categorization of depression as “exogenous” or “endogenous.”5 Exogenous depression was described as happening in the context of social stressors and as best treated with therapy. Endogenous depression was a supposedly truer form of depression as a disorder and was more biologically based. Patients suffering from endogenous depression were thought to have chemical abnormalities in the brain that could be alleviated by tricyclic antidepressants and subsequently SSRIs. Like many prior debates about depression, this one appears to be little discussed nowadays. A review of the use of the term “endogenous depression” in books shows an onset in the 1930s, a peak in the 1980s, and a rapid decline since.6
More recently, psychiatrists have defined depression using the DSM-5 criteria. Depression is thought to be the presence of at least five out of nine symptoms listed in the manual for a period of 2 weeks that cause significant distress or impairment.7 The DSM attempts to address criticism by providing information on its limitations and best use, and encourages clinical interpretation of symptoms. The DSM does not portray itself as a gold standard but rather as a tool for treatment planning and effective communication between peers. Furthermore, the National Institute on Mental Health is promoting an alternative understanding of depression using its own Research Domain Criteria, which attempt to provide a more objective understanding of the disorder based on biological rather than subjective correlates.
The growing literature on ketamine partly hinges on the belief that depression is something that can be redefined and changed at any moment. Many trials ask patients whether their depression remains in remission in the subsequent hours, days, and weeks following administration of the drug. However, one wonders if that is even possible. If a patient’s depression is alleviated in an hour, was it really clinical depression? Is it truly in remission? Contrary to our previous understanding, is depression, in reality, a switch that can be turned off by an infusion of an N-methyl-D-aspartate (NMDA)–receptor antagonist? Without minimizing the suffering of patients seeking ketamine or the relief provided to patients who benefit from the treatment, we simply are pointing out that the definition of depression did not account for this reported phenomenon of relatively instantaneous relief. The seemingly miraculous effects of ketamine suggest a new paradigm where any intervention – whether chemical, social, or psychological – could turn off the devastating effects of depression in an instant.
After all, the most widely used scale of depression, the nine-item Patient Health Questionnaire (PHQ-9) asks patients, “Over the last 2 weeks, how often have you been bothered by any of the following problems?” The highest answer one can give is “Nearly every day.” Are we incorrect to think that if one were suicidal every minute of the past 2 weeks, one would still score, nearly every day, even if one’s symptoms were relieved for the past hour? Thus, a maximum score of 27 would remain a 27 no matter what happened in the past hour.
We do realize that we are being overly literal. Ketamine makes some people feel better quickly, and researchers try to capture that effect by asking patients about their symptoms within short intervals. Furthermore, one has to start somewhere. After the infusion is a reasonable time to ask patients how they feel. We are also cognizant that many ketamine researchers do more long-term follow-ups and/or have recommended longer-term studies. Nonetheless,
Expanding our definition of depression to encompass experiences with short time frames may have unintended consequences. As living circumstances rarely change in minutes, the emphasis on rapid recovery makes the patients more in control of their reported experiences and thus their diagnoses. One cannot assess a patient’s impairment or disability from minute to minute. One is left with emphasizing the patient’s subjective symptoms and deemphasizing their relationships, goals, and daily functioning. How could one measure eating habits, hygiene, or participation in hobbies every hour? Another consequence of this reduced time frame is the expansion of a diagnosis that no longer requires the presence of symptoms for 2 weeks. Considering the already vast number of people diagnosed with depression,9,10 this small change may further expand the number diagnosed with a mood disorder. Perhaps to many practitioners and patients these arguments seem obtuse and fastidious, but there is a core failure in modern psychiatry to clearly differentiate the human condition from mental illness. Said failure has vast implications for psychiatric epidemiology, the sociological understanding of psychic suffering and suicide, as well as the overprescribing of psychotropic medications.
Ketamine is an exciting prospect to many psychiatrists who feel like we have had little advancement and few novel treatments in a long time; advertised breakthroughs in the treatment of depression since fluoxetine have not been particularly impressive. Furthermore, the concerns about potential ketamine abuse are not theoretical but a very real problem in some parts of the world.11,12 The concerns about abuse are worsened considering recent evidence that suggests that ketamine’s effect may be driven by its opiate rather than NMDA effects.13 While some have discussed those concerns, we think that the field also needs to address the fact that the debate about ketamine is also changing our definition of depression.
References
1. https://www.youtube.com/watch?v=MpcUN6XvGmk.
2. J Clin Psychiatry. 2016 Jun;77(6):e719-25.
3. Emerg (Tehran). 2014 Winter;2(1):36-9.
4. “Is esketamine the game-changer for depression we want?” Rolling Stone. 2019 Mar 11.
5. Psychol Med. 1971;1(3):191-6.
6. https://books.google.com/ngrams.
7. Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5). American Psychiatric Association, 2013.
8. Am J Psychiatry. 2014 Apr;171(4):395-7.
9. “Many people taking antidepressants discover they cannot quit.” New York Times. 2018 Apr 7.
10. “Antidepressants show greatest increase in number of prescription items dispensed.” National Health Service. 2015 Jul 5.
11. “The ketamine connection.” BBC News. 2015 Jul 10.
12. Front Psychiatry. 2018 Jul 17. doi: 10.33389/fpsyt.2018.00313.
13. Am J Psychiatry. 2018 Dec 1;175(2):1205-15.
Dr. Badre is a forensic psychiatrist in San Diego and an expert in correctional mental health. He holds teaching positions at the University of California, San Diego, and the University of San Diego. Among his writings is Coercion and the critical psychiatrist, chapter 7 in the new book “Critical Psychiatry: Controversies and Clinical Implications” (Cham, Switzerland: Springer Nature Switzerland, 2019, pp. 155-77). Dr. Lehman is an associate professor of psychiatry at UCSD. He is codirector of all Acute and Intensive Psychiatric Treatment at the VA Medical Center in San Diego, where he practices clinical psychiatry. He also is the course director for the UCSD third-year medical student psychiatry clerkship.
*This article was updated 3/25/2019.
What does it mean to define an amalgamation of symptoms as a “psychiatric disorder?” Are psychiatric disorders an extreme variation of normative human behavior? Is human behavior simply an output phenotype of some neurologic chemical processes that become disordered in mental illness? Can depression be localized in the brain and subsequently turned on or off? If depression were to be localized in the brain, would it be an excess of a neurotransmitter, the depletion of a receptor, a malfunctioning neuron, an overactive connectome, poorly processed genetic material, or something as yet undefined? Those questions always have been present in our minds and influenced our understanding of patients, but a recent development in psychiatry raises questions about one of the few things we were historically confident about.
A part of our foundational understanding of depression was that it is not sadness, per se. One can be sad for any amount of time. It is not uncommon to feel sad for any variety of reasons, such as watching an adorable 60-second commercial for dog food.1 Those fleeting moments of sadness can even be empowering; they remind us about the things we care about and would be sad to miss.
Sadness in oneself can demonstrate the experience of empathic sadness for others. On the contrary, depression appears to have little apparent purpose, and instead results in a maladaptive way of coping that is all-consuming and often very damaging. Depression is not a mood but a state of being, something that is not defined by how one feels but who one is or has become because of the disorder. So it comes as somewhat of a surprise when we heard that ketamine could alleviate depression in minutes.2,3 As described by a ketamine expert, symptoms are relieved in “no less than an hour.”4 The surprise is not so much that a treatment would work but that improvement could be defined in such a short time frame.
Psychiatry has debated the definition of depression for its entire existence. There are many ways to tackle the concept of depression. A lot of the debate has been about the causes of depression. One example of the continued evolution of our understanding of depression is our prior categorization of depression as “exogenous” or “endogenous.”5 Exogenous depression was described as happening in the context of social stressors and as best treated with therapy. Endogenous depression was a supposedly truer form of depression as a disorder and was more biologically based. Patients suffering from endogenous depression were thought to have chemical abnormalities in the brain that could be alleviated by tricyclic antidepressants and subsequently SSRIs. Like many prior debates about depression, this one appears to be little discussed nowadays. A review of the use of the term “endogenous depression” in books shows an onset in the 1930s, a peak in the 1980s, and a rapid decline since.6
More recently, psychiatrists have defined depression using the DSM-5 criteria. Depression is thought to be the presence of at least five out of nine symptoms listed in the manual for a period of 2 weeks that cause significant distress or impairment.7 The DSM attempts to address criticism by providing information on its limitations and best use, and encourages clinical interpretation of symptoms. The DSM does not portray itself as a gold standard but rather as a tool for treatment planning and effective communication between peers. Furthermore, the National Institute on Mental Health is promoting an alternative understanding of depression using its own Research Domain Criteria, which attempt to provide a more objective understanding of the disorder based on biological rather than subjective correlates.
The growing literature on ketamine partly hinges on the belief that depression is something that can be redefined and changed at any moment. Many trials ask patients whether their depression remains in remission in the subsequent hours, days, and weeks following administration of the drug. However, one wonders if that is even possible. If a patient’s depression is alleviated in an hour, was it really clinical depression? Is it truly in remission? Contrary to our previous understanding, is depression, in reality, a switch that can be turned off by an infusion of an N-methyl-D-aspartate (NMDA)–receptor antagonist? Without minimizing the suffering of patients seeking ketamine or the relief provided to patients who benefit from the treatment, we simply are pointing out that the definition of depression did not account for this reported phenomenon of relatively instantaneous relief. The seemingly miraculous effects of ketamine suggest a new paradigm where any intervention – whether chemical, social, or psychological – could turn off the devastating effects of depression in an instant.
After all, the most widely used scale of depression, the nine-item Patient Health Questionnaire (PHQ-9) asks patients, “Over the last 2 weeks, how often have you been bothered by any of the following problems?” The highest answer one can give is “Nearly every day.” Are we incorrect to think that if one were suicidal every minute of the past 2 weeks, one would still score, nearly every day, even if one’s symptoms were relieved for the past hour? Thus, a maximum score of 27 would remain a 27 no matter what happened in the past hour.
We do realize that we are being overly literal. Ketamine makes some people feel better quickly, and researchers try to capture that effect by asking patients about their symptoms within short intervals. Furthermore, one has to start somewhere. After the infusion is a reasonable time to ask patients how they feel. We are also cognizant that many ketamine researchers do more long-term follow-ups and/or have recommended longer-term studies. Nonetheless,
Expanding our definition of depression to encompass experiences with short time frames may have unintended consequences. As living circumstances rarely change in minutes, the emphasis on rapid recovery makes the patients more in control of their reported experiences and thus their diagnoses. One cannot assess a patient’s impairment or disability from minute to minute. One is left with emphasizing the patient’s subjective symptoms and deemphasizing their relationships, goals, and daily functioning. How could one measure eating habits, hygiene, or participation in hobbies every hour? Another consequence of this reduced time frame is the expansion of a diagnosis that no longer requires the presence of symptoms for 2 weeks. Considering the already vast number of people diagnosed with depression,9,10 this small change may further expand the number diagnosed with a mood disorder. Perhaps to many practitioners and patients these arguments seem obtuse and fastidious, but there is a core failure in modern psychiatry to clearly differentiate the human condition from mental illness. Said failure has vast implications for psychiatric epidemiology, the sociological understanding of psychic suffering and suicide, as well as the overprescribing of psychotropic medications.
Ketamine is an exciting prospect to many psychiatrists who feel like we have had little advancement and few novel treatments in a long time; advertised breakthroughs in the treatment of depression since fluoxetine have not been particularly impressive. Furthermore, the concerns about potential ketamine abuse are not theoretical but a very real problem in some parts of the world.11,12 The concerns about abuse are worsened considering recent evidence that suggests that ketamine’s effect may be driven by its opiate rather than NMDA effects.13 While some have discussed those concerns, we think that the field also needs to address the fact that the debate about ketamine is also changing our definition of depression.
References
1. https://www.youtube.com/watch?v=MpcUN6XvGmk.
2. J Clin Psychiatry. 2016 Jun;77(6):e719-25.
3. Emerg (Tehran). 2014 Winter;2(1):36-9.
4. “Is esketamine the game-changer for depression we want?” Rolling Stone. 2019 Mar 11.
5. Psychol Med. 1971;1(3):191-6.
6. https://books.google.com/ngrams.
7. Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5). American Psychiatric Association, 2013.
8. Am J Psychiatry. 2014 Apr;171(4):395-7.
9. “Many people taking antidepressants discover they cannot quit.” New York Times. 2018 Apr 7.
10. “Antidepressants show greatest increase in number of prescription items dispensed.” National Health Service. 2015 Jul 5.
11. “The ketamine connection.” BBC News. 2015 Jul 10.
12. Front Psychiatry. 2018 Jul 17. doi: 10.33389/fpsyt.2018.00313.
13. Am J Psychiatry. 2018 Dec 1;175(2):1205-15.
Dr. Badre is a forensic psychiatrist in San Diego and an expert in correctional mental health. He holds teaching positions at the University of California, San Diego, and the University of San Diego. Among his writings is Coercion and the critical psychiatrist, chapter 7 in the new book “Critical Psychiatry: Controversies and Clinical Implications” (Cham, Switzerland: Springer Nature Switzerland, 2019, pp. 155-77). Dr. Lehman is an associate professor of psychiatry at UCSD. He is codirector of all Acute and Intensive Psychiatric Treatment at the VA Medical Center in San Diego, where he practices clinical psychiatry. He also is the course director for the UCSD third-year medical student psychiatry clerkship.
*This article was updated 3/25/2019.
What does it mean to define an amalgamation of symptoms as a “psychiatric disorder?” Are psychiatric disorders an extreme variation of normative human behavior? Is human behavior simply an output phenotype of some neurologic chemical processes that become disordered in mental illness? Can depression be localized in the brain and subsequently turned on or off? If depression were to be localized in the brain, would it be an excess of a neurotransmitter, the depletion of a receptor, a malfunctioning neuron, an overactive connectome, poorly processed genetic material, or something as yet undefined? Those questions always have been present in our minds and influenced our understanding of patients, but a recent development in psychiatry raises questions about one of the few things we were historically confident about.
A part of our foundational understanding of depression was that it is not sadness, per se. One can be sad for any amount of time. It is not uncommon to feel sad for any variety of reasons, such as watching an adorable 60-second commercial for dog food.1 Those fleeting moments of sadness can even be empowering; they remind us about the things we care about and would be sad to miss.
Sadness in oneself can demonstrate the experience of empathic sadness for others. On the contrary, depression appears to have little apparent purpose, and instead results in a maladaptive way of coping that is all-consuming and often very damaging. Depression is not a mood but a state of being, something that is not defined by how one feels but who one is or has become because of the disorder. So it comes as somewhat of a surprise when we heard that ketamine could alleviate depression in minutes.2,3 As described by a ketamine expert, symptoms are relieved in “no less than an hour.”4 The surprise is not so much that a treatment would work but that improvement could be defined in such a short time frame.
Psychiatry has debated the definition of depression for its entire existence. There are many ways to tackle the concept of depression. A lot of the debate has been about the causes of depression. One example of the continued evolution of our understanding of depression is our prior categorization of depression as “exogenous” or “endogenous.”5 Exogenous depression was described as happening in the context of social stressors and as best treated with therapy. Endogenous depression was a supposedly truer form of depression as a disorder and was more biologically based. Patients suffering from endogenous depression were thought to have chemical abnormalities in the brain that could be alleviated by tricyclic antidepressants and subsequently SSRIs. Like many prior debates about depression, this one appears to be little discussed nowadays. A review of the use of the term “endogenous depression” in books shows an onset in the 1930s, a peak in the 1980s, and a rapid decline since.6
More recently, psychiatrists have defined depression using the DSM-5 criteria. Depression is thought to be the presence of at least five out of nine symptoms listed in the manual for a period of 2 weeks that cause significant distress or impairment.7 The DSM attempts to address criticism by providing information on its limitations and best use, and encourages clinical interpretation of symptoms. The DSM does not portray itself as a gold standard but rather as a tool for treatment planning and effective communication between peers. Furthermore, the National Institute on Mental Health is promoting an alternative understanding of depression using its own Research Domain Criteria, which attempt to provide a more objective understanding of the disorder based on biological rather than subjective correlates.
The growing literature on ketamine partly hinges on the belief that depression is something that can be redefined and changed at any moment. Many trials ask patients whether their depression remains in remission in the subsequent hours, days, and weeks following administration of the drug. However, one wonders if that is even possible. If a patient’s depression is alleviated in an hour, was it really clinical depression? Is it truly in remission? Contrary to our previous understanding, is depression, in reality, a switch that can be turned off by an infusion of an N-methyl-D-aspartate (NMDA)–receptor antagonist? Without minimizing the suffering of patients seeking ketamine or the relief provided to patients who benefit from the treatment, we simply are pointing out that the definition of depression did not account for this reported phenomenon of relatively instantaneous relief. The seemingly miraculous effects of ketamine suggest a new paradigm where any intervention – whether chemical, social, or psychological – could turn off the devastating effects of depression in an instant.
After all, the most widely used scale of depression, the nine-item Patient Health Questionnaire (PHQ-9) asks patients, “Over the last 2 weeks, how often have you been bothered by any of the following problems?” The highest answer one can give is “Nearly every day.” Are we incorrect to think that if one were suicidal every minute of the past 2 weeks, one would still score, nearly every day, even if one’s symptoms were relieved for the past hour? Thus, a maximum score of 27 would remain a 27 no matter what happened in the past hour.
We do realize that we are being overly literal. Ketamine makes some people feel better quickly, and researchers try to capture that effect by asking patients about their symptoms within short intervals. Furthermore, one has to start somewhere. After the infusion is a reasonable time to ask patients how they feel. We are also cognizant that many ketamine researchers do more long-term follow-ups and/or have recommended longer-term studies. Nonetheless,
Expanding our definition of depression to encompass experiences with short time frames may have unintended consequences. As living circumstances rarely change in minutes, the emphasis on rapid recovery makes the patients more in control of their reported experiences and thus their diagnoses. One cannot assess a patient’s impairment or disability from minute to minute. One is left with emphasizing the patient’s subjective symptoms and deemphasizing their relationships, goals, and daily functioning. How could one measure eating habits, hygiene, or participation in hobbies every hour? Another consequence of this reduced time frame is the expansion of a diagnosis that no longer requires the presence of symptoms for 2 weeks. Considering the already vast number of people diagnosed with depression,9,10 this small change may further expand the number diagnosed with a mood disorder. Perhaps to many practitioners and patients these arguments seem obtuse and fastidious, but there is a core failure in modern psychiatry to clearly differentiate the human condition from mental illness. Said failure has vast implications for psychiatric epidemiology, the sociological understanding of psychic suffering and suicide, as well as the overprescribing of psychotropic medications.
Ketamine is an exciting prospect to many psychiatrists who feel like we have had little advancement and few novel treatments in a long time; advertised breakthroughs in the treatment of depression since fluoxetine have not been particularly impressive. Furthermore, the concerns about potential ketamine abuse are not theoretical but a very real problem in some parts of the world.11,12 The concerns about abuse are worsened considering recent evidence that suggests that ketamine’s effect may be driven by its opiate rather than NMDA effects.13 While some have discussed those concerns, we think that the field also needs to address the fact that the debate about ketamine is also changing our definition of depression.
References
1. https://www.youtube.com/watch?v=MpcUN6XvGmk.
2. J Clin Psychiatry. 2016 Jun;77(6):e719-25.
3. Emerg (Tehran). 2014 Winter;2(1):36-9.
4. “Is esketamine the game-changer for depression we want?” Rolling Stone. 2019 Mar 11.
5. Psychol Med. 1971;1(3):191-6.
6. https://books.google.com/ngrams.
7. Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5). American Psychiatric Association, 2013.
8. Am J Psychiatry. 2014 Apr;171(4):395-7.
9. “Many people taking antidepressants discover they cannot quit.” New York Times. 2018 Apr 7.
10. “Antidepressants show greatest increase in number of prescription items dispensed.” National Health Service. 2015 Jul 5.
11. “The ketamine connection.” BBC News. 2015 Jul 10.
12. Front Psychiatry. 2018 Jul 17. doi: 10.33389/fpsyt.2018.00313.
13. Am J Psychiatry. 2018 Dec 1;175(2):1205-15.
Dr. Badre is a forensic psychiatrist in San Diego and an expert in correctional mental health. He holds teaching positions at the University of California, San Diego, and the University of San Diego. Among his writings is Coercion and the critical psychiatrist, chapter 7 in the new book “Critical Psychiatry: Controversies and Clinical Implications” (Cham, Switzerland: Springer Nature Switzerland, 2019, pp. 155-77). Dr. Lehman is an associate professor of psychiatry at UCSD. He is codirector of all Acute and Intensive Psychiatric Treatment at the VA Medical Center in San Diego, where he practices clinical psychiatry. He also is the course director for the UCSD third-year medical student psychiatry clerkship.
*This article was updated 3/25/2019.
Spring
There is little to want for living in San Diego, America’s Finest City. The weather here is 72 and sunny year round. Yet, there are shortcomings. For one, there are no Forsythia. Forsythia are the deciduous shrubs that act as the harbingers of spring, blooming brilliant yellow across cold gray damp parts of the United States right now.
I grew up in New England where Forsythia bushes flower this time of year – a most welcome sign that the winter’s worst was over. Along with the purple crocus plants popping up in the warm bits of grass that breaks through the snow, seeing the Forsythia bloom always evoked that most appealing of feelings, hope. Hope that the discomfort of winter has passed. Hope that the beauty of nature will return. A promise that this year’s cycle of life will continue.
. A future with less suffering or with more joy. And as their doctors, we can help them get there.
A newly insured patient came to see me today. She had severe psoriasis. Her face, masked with red scaly patches, was heavy with the burden of the long winter she had endured. She was itchy and flaky and so embarrassed as to struggle to make eye contact with me. When I told her that we could help her, that there are treatments for her that would clear up the psoriasis and relieve her symptoms, she started to cry. Her husband intervened, apologizing for her. “I’m sorry. She has had this for so long, and you are the first person to tell her that she can get better. You have given us hope.”
When I walked back to my office I noticed the Rhode Island flag that I have mounted. Under the stars and blue anchor on it is the word “hope.” In 1664, when the state seal was created, it was the most important of ideas. It is why the settlers of Rhode Island risked their lives to cross an ocean to start anew, why my ancestors came from Italy two centuries later, why my parents sent me to college, why I decided to try for medicine. It is what most of us give every day. Hope, the ability to see into the future and bring that feeling back to the present. The belief that whatever and wherever you are, soon it will be even better. It cannot, however, be commanded. You can’t insist a patient hope any more than you can make them love. You must first understand what they see and feel, then show them how things might be better through trust.
Throughout life, hope creates possibilities. It unites us. It motivates us. It is the destroyer of winter and of burnout and of disease. It is one of the most important gifts that we give patients, and we do it everyday. Tomorrow in your practice, notice how often you foster it. Pay attention to how your patient changes the moment you give it to them. Watch the Forsythia bloom as you reassure them that their spring will return again.
“We must accept finite disappointment, but never lose infinite hope.” – Martin Luther King Jr.
Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on Twitter. Write to him at dermnews@mdedge.com.
There is little to want for living in San Diego, America’s Finest City. The weather here is 72 and sunny year round. Yet, there are shortcomings. For one, there are no Forsythia. Forsythia are the deciduous shrubs that act as the harbingers of spring, blooming brilliant yellow across cold gray damp parts of the United States right now.
I grew up in New England where Forsythia bushes flower this time of year – a most welcome sign that the winter’s worst was over. Along with the purple crocus plants popping up in the warm bits of grass that breaks through the snow, seeing the Forsythia bloom always evoked that most appealing of feelings, hope. Hope that the discomfort of winter has passed. Hope that the beauty of nature will return. A promise that this year’s cycle of life will continue.
. A future with less suffering or with more joy. And as their doctors, we can help them get there.
A newly insured patient came to see me today. She had severe psoriasis. Her face, masked with red scaly patches, was heavy with the burden of the long winter she had endured. She was itchy and flaky and so embarrassed as to struggle to make eye contact with me. When I told her that we could help her, that there are treatments for her that would clear up the psoriasis and relieve her symptoms, she started to cry. Her husband intervened, apologizing for her. “I’m sorry. She has had this for so long, and you are the first person to tell her that she can get better. You have given us hope.”
When I walked back to my office I noticed the Rhode Island flag that I have mounted. Under the stars and blue anchor on it is the word “hope.” In 1664, when the state seal was created, it was the most important of ideas. It is why the settlers of Rhode Island risked their lives to cross an ocean to start anew, why my ancestors came from Italy two centuries later, why my parents sent me to college, why I decided to try for medicine. It is what most of us give every day. Hope, the ability to see into the future and bring that feeling back to the present. The belief that whatever and wherever you are, soon it will be even better. It cannot, however, be commanded. You can’t insist a patient hope any more than you can make them love. You must first understand what they see and feel, then show them how things might be better through trust.
Throughout life, hope creates possibilities. It unites us. It motivates us. It is the destroyer of winter and of burnout and of disease. It is one of the most important gifts that we give patients, and we do it everyday. Tomorrow in your practice, notice how often you foster it. Pay attention to how your patient changes the moment you give it to them. Watch the Forsythia bloom as you reassure them that their spring will return again.
“We must accept finite disappointment, but never lose infinite hope.” – Martin Luther King Jr.
Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on Twitter. Write to him at dermnews@mdedge.com.
There is little to want for living in San Diego, America’s Finest City. The weather here is 72 and sunny year round. Yet, there are shortcomings. For one, there are no Forsythia. Forsythia are the deciduous shrubs that act as the harbingers of spring, blooming brilliant yellow across cold gray damp parts of the United States right now.
I grew up in New England where Forsythia bushes flower this time of year – a most welcome sign that the winter’s worst was over. Along with the purple crocus plants popping up in the warm bits of grass that breaks through the snow, seeing the Forsythia bloom always evoked that most appealing of feelings, hope. Hope that the discomfort of winter has passed. Hope that the beauty of nature will return. A promise that this year’s cycle of life will continue.
. A future with less suffering or with more joy. And as their doctors, we can help them get there.
A newly insured patient came to see me today. She had severe psoriasis. Her face, masked with red scaly patches, was heavy with the burden of the long winter she had endured. She was itchy and flaky and so embarrassed as to struggle to make eye contact with me. When I told her that we could help her, that there are treatments for her that would clear up the psoriasis and relieve her symptoms, she started to cry. Her husband intervened, apologizing for her. “I’m sorry. She has had this for so long, and you are the first person to tell her that she can get better. You have given us hope.”
When I walked back to my office I noticed the Rhode Island flag that I have mounted. Under the stars and blue anchor on it is the word “hope.” In 1664, when the state seal was created, it was the most important of ideas. It is why the settlers of Rhode Island risked their lives to cross an ocean to start anew, why my ancestors came from Italy two centuries later, why my parents sent me to college, why I decided to try for medicine. It is what most of us give every day. Hope, the ability to see into the future and bring that feeling back to the present. The belief that whatever and wherever you are, soon it will be even better. It cannot, however, be commanded. You can’t insist a patient hope any more than you can make them love. You must first understand what they see and feel, then show them how things might be better through trust.
Throughout life, hope creates possibilities. It unites us. It motivates us. It is the destroyer of winter and of burnout and of disease. It is one of the most important gifts that we give patients, and we do it everyday. Tomorrow in your practice, notice how often you foster it. Pay attention to how your patient changes the moment you give it to them. Watch the Forsythia bloom as you reassure them that their spring will return again.
“We must accept finite disappointment, but never lose infinite hope.” – Martin Luther King Jr.
Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on Twitter. Write to him at dermnews@mdedge.com.
Unintended consequences in the drive to simplify computerized test ordering
“X marks the spot!”
It’s one of the classic pirate tropes, bringing to mind images of Long John Silver, buried treasure, and a secret map with an “X” to show the hidden gold.
Today that “X” (or, in some cases, a check mark or radio button) seems to be indicating where the money is to be lost, rather than found.
Hospital computer systems are increasingly reliant on preprogrammed order lists that you check off rather than the actual test itself. We’ve gone from having to write out the tests we want, to typing them into a box, to checking them off with a mouse.
I’ve seen systems where you’re offered a menu such as:
A. Brain MRI (noncontrast)
B. Brain MRI (w/wo contrast)
C. Head MRA (noncontrast)
D. Head MRA (with contrast)
E. Neck MRA (noncontrast)
F. Neck MRA (with contrast)
G. Brain MRI and head/neck MRA (noncontrast)
H. Brain MRI and head/neck MRA (w/wo contrast)
And that’s just for the brain and its vascular supply. Expand that to the rest of the nervous system, then to the whole body, then to other tests (labs) ... and you get the idea.
I suppose the driving force here is to make the system easier to use. Doctors are busy. It saves time just have to check a box if you want three tests, rather than note all of them individually.
But it’s really not that hard to check off three. Probably less than 5 seconds (as of my last time on call). And this is where, to me, X marks the spot where the money isn’t.
Humans, like most animals, are pretty good at defaulting to a low-energy setting. So if you only have to check off one box instead of three, or five, or whatever, why bother?
If the patient is being admitted for a stroke/TIA, then it makes sense to do the brain MRI and head/neck MRA. But what if it’s just headaches, or a new seizure, or a concussion? I see plenty of times when more tests are done than necessary, simply because the ordering physician either didn’t know what was really needed or because it was easier to just check the box.
This is not, in my experience, rare. I’d say anywhere from one-third to half of patients I’ve consulted on had an overkill neurological work-up, in which tests with no medical indications had been ordered. They’ve generally already been put in the system, or even done, before I get to the bedside.
I suppose one could say they should wait for the specialist to get there before any of the costly tests are ordered, but that opens up another can of worms. What if a critical finding that needed to be acted upon isn’t found in time because of such a rule? Not only that, but waiting for me to show up and order tests means it will take longer to get them done, adding onto the hospital stay, and (again) running up costs.
So that’s not an answer, either. There really isn’t one, unfortunately.
But, in our haste to make things easier, or faster, or even just flashier, the trend seems to be at the cost of doing things reasonably. At the same time that we’re trying to save money, the single “X” may be marking the spot where we’re actually throwing it away.
Dr. Block has a solo neurology practice in Scottsdale, Ariz.
“X marks the spot!”
It’s one of the classic pirate tropes, bringing to mind images of Long John Silver, buried treasure, and a secret map with an “X” to show the hidden gold.
Today that “X” (or, in some cases, a check mark or radio button) seems to be indicating where the money is to be lost, rather than found.
Hospital computer systems are increasingly reliant on preprogrammed order lists that you check off rather than the actual test itself. We’ve gone from having to write out the tests we want, to typing them into a box, to checking them off with a mouse.
I’ve seen systems where you’re offered a menu such as:
A. Brain MRI (noncontrast)
B. Brain MRI (w/wo contrast)
C. Head MRA (noncontrast)
D. Head MRA (with contrast)
E. Neck MRA (noncontrast)
F. Neck MRA (with contrast)
G. Brain MRI and head/neck MRA (noncontrast)
H. Brain MRI and head/neck MRA (w/wo contrast)
And that’s just for the brain and its vascular supply. Expand that to the rest of the nervous system, then to the whole body, then to other tests (labs) ... and you get the idea.
I suppose the driving force here is to make the system easier to use. Doctors are busy. It saves time just have to check a box if you want three tests, rather than note all of them individually.
But it’s really not that hard to check off three. Probably less than 5 seconds (as of my last time on call). And this is where, to me, X marks the spot where the money isn’t.
Humans, like most animals, are pretty good at defaulting to a low-energy setting. So if you only have to check off one box instead of three, or five, or whatever, why bother?
If the patient is being admitted for a stroke/TIA, then it makes sense to do the brain MRI and head/neck MRA. But what if it’s just headaches, or a new seizure, or a concussion? I see plenty of times when more tests are done than necessary, simply because the ordering physician either didn’t know what was really needed or because it was easier to just check the box.
This is not, in my experience, rare. I’d say anywhere from one-third to half of patients I’ve consulted on had an overkill neurological work-up, in which tests with no medical indications had been ordered. They’ve generally already been put in the system, or even done, before I get to the bedside.
I suppose one could say they should wait for the specialist to get there before any of the costly tests are ordered, but that opens up another can of worms. What if a critical finding that needed to be acted upon isn’t found in time because of such a rule? Not only that, but waiting for me to show up and order tests means it will take longer to get them done, adding onto the hospital stay, and (again) running up costs.
So that’s not an answer, either. There really isn’t one, unfortunately.
But, in our haste to make things easier, or faster, or even just flashier, the trend seems to be at the cost of doing things reasonably. At the same time that we’re trying to save money, the single “X” may be marking the spot where we’re actually throwing it away.
Dr. Block has a solo neurology practice in Scottsdale, Ariz.
“X marks the spot!”
It’s one of the classic pirate tropes, bringing to mind images of Long John Silver, buried treasure, and a secret map with an “X” to show the hidden gold.
Today that “X” (or, in some cases, a check mark or radio button) seems to be indicating where the money is to be lost, rather than found.
Hospital computer systems are increasingly reliant on preprogrammed order lists that you check off rather than the actual test itself. We’ve gone from having to write out the tests we want, to typing them into a box, to checking them off with a mouse.
I’ve seen systems where you’re offered a menu such as:
A. Brain MRI (noncontrast)
B. Brain MRI (w/wo contrast)
C. Head MRA (noncontrast)
D. Head MRA (with contrast)
E. Neck MRA (noncontrast)
F. Neck MRA (with contrast)
G. Brain MRI and head/neck MRA (noncontrast)
H. Brain MRI and head/neck MRA (w/wo contrast)
And that’s just for the brain and its vascular supply. Expand that to the rest of the nervous system, then to the whole body, then to other tests (labs) ... and you get the idea.
I suppose the driving force here is to make the system easier to use. Doctors are busy. It saves time just have to check a box if you want three tests, rather than note all of them individually.
But it’s really not that hard to check off three. Probably less than 5 seconds (as of my last time on call). And this is where, to me, X marks the spot where the money isn’t.
Humans, like most animals, are pretty good at defaulting to a low-energy setting. So if you only have to check off one box instead of three, or five, or whatever, why bother?
If the patient is being admitted for a stroke/TIA, then it makes sense to do the brain MRI and head/neck MRA. But what if it’s just headaches, or a new seizure, or a concussion? I see plenty of times when more tests are done than necessary, simply because the ordering physician either didn’t know what was really needed or because it was easier to just check the box.
This is not, in my experience, rare. I’d say anywhere from one-third to half of patients I’ve consulted on had an overkill neurological work-up, in which tests with no medical indications had been ordered. They’ve generally already been put in the system, or even done, before I get to the bedside.
I suppose one could say they should wait for the specialist to get there before any of the costly tests are ordered, but that opens up another can of worms. What if a critical finding that needed to be acted upon isn’t found in time because of such a rule? Not only that, but waiting for me to show up and order tests means it will take longer to get them done, adding onto the hospital stay, and (again) running up costs.
So that’s not an answer, either. There really isn’t one, unfortunately.
But, in our haste to make things easier, or faster, or even just flashier, the trend seems to be at the cost of doing things reasonably. At the same time that we’re trying to save money, the single “X” may be marking the spot where we’re actually throwing it away.
Dr. Block has a solo neurology practice in Scottsdale, Ariz.
A new era of TTP treatment
Earlier this year, the Food and Drug Administration approved Cablivi (caplacizumab-yhdp) (Sanofi Genzyme, Cambridge, Mass.) for the treatment of acquired thrombotic thrombocytopenic purpura (TTP), making it the first medication specifically indicated for the treatment of TTP.
The approval of caplacizumab and the clinical trial results that approval is based on are the most promising developments in the treatment of TTP since the introduction of plasma exchange (PE) therapy. However, many questions remain about how to best administer caplacizumab, specifically, which patients should receive it? Should all TTP patients start on caplacizumab therapy or should it be limited to patients with histories of TTP or those slow to respond to standard therapy with PE and immunosuppression?
TTP is a rare thrombotic microangiopathy characterized by thrombocytopenia and microangiopathic hemolytic anemia caused by the inhibition of ADAMTS13, a metalloproteinase, which cleaves large-molecular-weight von Willebrand factor (vWF) multimers. Caplacizumab is a humanized bivalent, variable domain-only immunoglobulin fragment. The drug targets the A1 domain of vWF and inhibits the binding between vWF and the platelet glycoprotein Ib-IX-V receptor, preventing the formation of the microvascular thrombi and platelet loss associated with TTP.
FDA approval of caplacizumab came shortly after the publication of the results of the HERCULES trial in the New England Journal of Medicine by Marie Scully, MD, and her colleagues (N Engl J Med. 2019; 380[4]: 335-46).
HERCULES was an international phase 3, double blinded, placebo-controlled, randomized study designed to evaluate the efficacy and safety of caplacizumab. In total, 145 patients participated in the trial. Caplacizumab or placebo were given in addition to standard therapy of plasma exchange (PE) and immunosuppression. Caplacizumab or placebo were administered as an intravenous loading dose prior to the first PE after randomization and subcutaneously once daily until 30 days after the last PE. All patients received daily PE until 2 days after platelet count normalization.
The primary measure of the study was the time to platelet count response of greater than 150 x 109/L following the cessation of daily PE. Secondary measures included TTP-related death; TTP relapse; major thromboembolic events; proportion of subjects with refractory TTP; normalization of organ damage markers including lactate dehydrogenase, cardiac troponin I, and serum creatinine; and other adverse events.
The authors found that the median time of normalization of the platelet count was shorter in the caplacizumab group, compared with placebo, with the caplacizumab group being 1.55 times more likely to have a normalized platelet count at any given time point in the study. While statistically significant differences were identified in the rate of platelet normalization, the median number of days of PE until normalization was only 2 days less in the caplacizumab group (five treatments) than in the placebo group (seven treatments), which may not be clinically significant for the treating physician.
In fact, the secondary endpoints of the study seem much more clinically promising in the treatment of TTP. The composite rate of TTP-related death, TTP recurrence, or major thromboembolic events during the treatment period was significantly lower in the caplacizumab group (12%) versus placebo (49%). No TTP-related deaths occurred in the caplacizumab group. The caplacizumab group was also statistically less likely to have a TTP exacerbation, defined as disease recurrence within 30 days from the last PE, than the placebo group.
End organ damage serum markers also improved faster in the caplacizumab group, although there was no significant difference between groups. Overall hospitalization (median of 9 vs. 12 days) and ICU stays (median of 3 vs. 5 days) were shorter in the caplacizumab group, compared with the placebo group.
While several relapses, defined as disease recurrence after 30 days from the last PE, occurred in the caplacizumab group, the relapses were only found in patients with ADAMTS13 activity of less than 10% at the end of the treatment period. Mild side effects, such as mucocutaneous bleeding were more frequent in the caplacizumab group. No major bleeding complications were observed.
The HERCULES trial generates more questions about the role of ADAMTS13 activity testing to monitor treatment response and to make therapy decisions. Extremely low ADAMTS13 activity levels at the cessation of therapy may be a sign of treatment inadequacy and may warrant closer follow-up of at-risk patients on caplacizumab.
Sanofi Genzyme estimates that the U.S. list price will be approximately $270,000 for a standard treatment course, according to a news release from the company. Whether payers will add it to formularies remains uncertain, but the high drug cost may be countered by potential savings in the reduction of hospital and ICU days with caplacizumab therapy. Sanofi Genzyme will also have a patient support program for eligible patients.
Caplacizumab has been approved in Europe since August 2018, but is not readily available in the United States. Given the dearth of clinical experience with the drug outside of the TITAN and HERCULES trials, strong recommendations for when and how to initiate therapy remain elusive.
As caplacizumab is further introduced into clinical practice, more studies are needed to identify which patient groups will benefit most from therapy. The current data for caplacizumab shows that it will be used as an adjunct to standard PE therapy, rather than as a replacement. How the drug is used in combination with current TTP treatments – such as corticosteroids, rituximab, bortezomib, vincristine, N-acetylcysteine, and splenectomy – should be evaluated to identify which treatment combinations not only improve platelet counts, but also reduce mortality and morbidity while remaining cost effective.
Dr. Ricci is a staff physician and Apheresis Director at the Taussig Cancer Institute at the Cleveland Clinic. She reported having no conflicts of interest.
Earlier this year, the Food and Drug Administration approved Cablivi (caplacizumab-yhdp) (Sanofi Genzyme, Cambridge, Mass.) for the treatment of acquired thrombotic thrombocytopenic purpura (TTP), making it the first medication specifically indicated for the treatment of TTP.
The approval of caplacizumab and the clinical trial results that approval is based on are the most promising developments in the treatment of TTP since the introduction of plasma exchange (PE) therapy. However, many questions remain about how to best administer caplacizumab, specifically, which patients should receive it? Should all TTP patients start on caplacizumab therapy or should it be limited to patients with histories of TTP or those slow to respond to standard therapy with PE and immunosuppression?
TTP is a rare thrombotic microangiopathy characterized by thrombocytopenia and microangiopathic hemolytic anemia caused by the inhibition of ADAMTS13, a metalloproteinase, which cleaves large-molecular-weight von Willebrand factor (vWF) multimers. Caplacizumab is a humanized bivalent, variable domain-only immunoglobulin fragment. The drug targets the A1 domain of vWF and inhibits the binding between vWF and the platelet glycoprotein Ib-IX-V receptor, preventing the formation of the microvascular thrombi and platelet loss associated with TTP.
FDA approval of caplacizumab came shortly after the publication of the results of the HERCULES trial in the New England Journal of Medicine by Marie Scully, MD, and her colleagues (N Engl J Med. 2019; 380[4]: 335-46).
HERCULES was an international phase 3, double blinded, placebo-controlled, randomized study designed to evaluate the efficacy and safety of caplacizumab. In total, 145 patients participated in the trial. Caplacizumab or placebo were given in addition to standard therapy of plasma exchange (PE) and immunosuppression. Caplacizumab or placebo were administered as an intravenous loading dose prior to the first PE after randomization and subcutaneously once daily until 30 days after the last PE. All patients received daily PE until 2 days after platelet count normalization.
The primary measure of the study was the time to platelet count response of greater than 150 x 109/L following the cessation of daily PE. Secondary measures included TTP-related death; TTP relapse; major thromboembolic events; proportion of subjects with refractory TTP; normalization of organ damage markers including lactate dehydrogenase, cardiac troponin I, and serum creatinine; and other adverse events.
The authors found that the median time of normalization of the platelet count was shorter in the caplacizumab group, compared with placebo, with the caplacizumab group being 1.55 times more likely to have a normalized platelet count at any given time point in the study. While statistically significant differences were identified in the rate of platelet normalization, the median number of days of PE until normalization was only 2 days less in the caplacizumab group (five treatments) than in the placebo group (seven treatments), which may not be clinically significant for the treating physician.
In fact, the secondary endpoints of the study seem much more clinically promising in the treatment of TTP. The composite rate of TTP-related death, TTP recurrence, or major thromboembolic events during the treatment period was significantly lower in the caplacizumab group (12%) versus placebo (49%). No TTP-related deaths occurred in the caplacizumab group. The caplacizumab group was also statistically less likely to have a TTP exacerbation, defined as disease recurrence within 30 days from the last PE, than the placebo group.
End organ damage serum markers also improved faster in the caplacizumab group, although there was no significant difference between groups. Overall hospitalization (median of 9 vs. 12 days) and ICU stays (median of 3 vs. 5 days) were shorter in the caplacizumab group, compared with the placebo group.
While several relapses, defined as disease recurrence after 30 days from the last PE, occurred in the caplacizumab group, the relapses were only found in patients with ADAMTS13 activity of less than 10% at the end of the treatment period. Mild side effects, such as mucocutaneous bleeding were more frequent in the caplacizumab group. No major bleeding complications were observed.
The HERCULES trial generates more questions about the role of ADAMTS13 activity testing to monitor treatment response and to make therapy decisions. Extremely low ADAMTS13 activity levels at the cessation of therapy may be a sign of treatment inadequacy and may warrant closer follow-up of at-risk patients on caplacizumab.
Sanofi Genzyme estimates that the U.S. list price will be approximately $270,000 for a standard treatment course, according to a news release from the company. Whether payers will add it to formularies remains uncertain, but the high drug cost may be countered by potential savings in the reduction of hospital and ICU days with caplacizumab therapy. Sanofi Genzyme will also have a patient support program for eligible patients.
Caplacizumab has been approved in Europe since August 2018, but is not readily available in the United States. Given the dearth of clinical experience with the drug outside of the TITAN and HERCULES trials, strong recommendations for when and how to initiate therapy remain elusive.
As caplacizumab is further introduced into clinical practice, more studies are needed to identify which patient groups will benefit most from therapy. The current data for caplacizumab shows that it will be used as an adjunct to standard PE therapy, rather than as a replacement. How the drug is used in combination with current TTP treatments – such as corticosteroids, rituximab, bortezomib, vincristine, N-acetylcysteine, and splenectomy – should be evaluated to identify which treatment combinations not only improve platelet counts, but also reduce mortality and morbidity while remaining cost effective.
Dr. Ricci is a staff physician and Apheresis Director at the Taussig Cancer Institute at the Cleveland Clinic. She reported having no conflicts of interest.
Earlier this year, the Food and Drug Administration approved Cablivi (caplacizumab-yhdp) (Sanofi Genzyme, Cambridge, Mass.) for the treatment of acquired thrombotic thrombocytopenic purpura (TTP), making it the first medication specifically indicated for the treatment of TTP.
The approval of caplacizumab and the clinical trial results that approval is based on are the most promising developments in the treatment of TTP since the introduction of plasma exchange (PE) therapy. However, many questions remain about how to best administer caplacizumab, specifically, which patients should receive it? Should all TTP patients start on caplacizumab therapy or should it be limited to patients with histories of TTP or those slow to respond to standard therapy with PE and immunosuppression?
TTP is a rare thrombotic microangiopathy characterized by thrombocytopenia and microangiopathic hemolytic anemia caused by the inhibition of ADAMTS13, a metalloproteinase, which cleaves large-molecular-weight von Willebrand factor (vWF) multimers. Caplacizumab is a humanized bivalent, variable domain-only immunoglobulin fragment. The drug targets the A1 domain of vWF and inhibits the binding between vWF and the platelet glycoprotein Ib-IX-V receptor, preventing the formation of the microvascular thrombi and platelet loss associated with TTP.
FDA approval of caplacizumab came shortly after the publication of the results of the HERCULES trial in the New England Journal of Medicine by Marie Scully, MD, and her colleagues (N Engl J Med. 2019; 380[4]: 335-46).
HERCULES was an international phase 3, double blinded, placebo-controlled, randomized study designed to evaluate the efficacy and safety of caplacizumab. In total, 145 patients participated in the trial. Caplacizumab or placebo were given in addition to standard therapy of plasma exchange (PE) and immunosuppression. Caplacizumab or placebo were administered as an intravenous loading dose prior to the first PE after randomization and subcutaneously once daily until 30 days after the last PE. All patients received daily PE until 2 days after platelet count normalization.
The primary measure of the study was the time to platelet count response of greater than 150 x 109/L following the cessation of daily PE. Secondary measures included TTP-related death; TTP relapse; major thromboembolic events; proportion of subjects with refractory TTP; normalization of organ damage markers including lactate dehydrogenase, cardiac troponin I, and serum creatinine; and other adverse events.
The authors found that the median time of normalization of the platelet count was shorter in the caplacizumab group, compared with placebo, with the caplacizumab group being 1.55 times more likely to have a normalized platelet count at any given time point in the study. While statistically significant differences were identified in the rate of platelet normalization, the median number of days of PE until normalization was only 2 days less in the caplacizumab group (five treatments) than in the placebo group (seven treatments), which may not be clinically significant for the treating physician.
In fact, the secondary endpoints of the study seem much more clinically promising in the treatment of TTP. The composite rate of TTP-related death, TTP recurrence, or major thromboembolic events during the treatment period was significantly lower in the caplacizumab group (12%) versus placebo (49%). No TTP-related deaths occurred in the caplacizumab group. The caplacizumab group was also statistically less likely to have a TTP exacerbation, defined as disease recurrence within 30 days from the last PE, than the placebo group.
End organ damage serum markers also improved faster in the caplacizumab group, although there was no significant difference between groups. Overall hospitalization (median of 9 vs. 12 days) and ICU stays (median of 3 vs. 5 days) were shorter in the caplacizumab group, compared with the placebo group.
While several relapses, defined as disease recurrence after 30 days from the last PE, occurred in the caplacizumab group, the relapses were only found in patients with ADAMTS13 activity of less than 10% at the end of the treatment period. Mild side effects, such as mucocutaneous bleeding were more frequent in the caplacizumab group. No major bleeding complications were observed.
The HERCULES trial generates more questions about the role of ADAMTS13 activity testing to monitor treatment response and to make therapy decisions. Extremely low ADAMTS13 activity levels at the cessation of therapy may be a sign of treatment inadequacy and may warrant closer follow-up of at-risk patients on caplacizumab.
Sanofi Genzyme estimates that the U.S. list price will be approximately $270,000 for a standard treatment course, according to a news release from the company. Whether payers will add it to formularies remains uncertain, but the high drug cost may be countered by potential savings in the reduction of hospital and ICU days with caplacizumab therapy. Sanofi Genzyme will also have a patient support program for eligible patients.
Caplacizumab has been approved in Europe since August 2018, but is not readily available in the United States. Given the dearth of clinical experience with the drug outside of the TITAN and HERCULES trials, strong recommendations for when and how to initiate therapy remain elusive.
As caplacizumab is further introduced into clinical practice, more studies are needed to identify which patient groups will benefit most from therapy. The current data for caplacizumab shows that it will be used as an adjunct to standard PE therapy, rather than as a replacement. How the drug is used in combination with current TTP treatments – such as corticosteroids, rituximab, bortezomib, vincristine, N-acetylcysteine, and splenectomy – should be evaluated to identify which treatment combinations not only improve platelet counts, but also reduce mortality and morbidity while remaining cost effective.
Dr. Ricci is a staff physician and Apheresis Director at the Taussig Cancer Institute at the Cleveland Clinic. She reported having no conflicts of interest.
For Latino patients, mental illness often goes untreated
Intergenerational trauma, attitudes can allow cycles of depression, anxiety to continue
The stigma tied to mental illness can be particularly difficult to overcome for people of Latin American descent, writes Concepción de León in El Espace, a column in the New York Times focused on news and culture relevant to Latinx communities. Sometimes those seeking help run into familiar mantras. “Let me know if any of these sound familiar: 'Boys don’t cry. We don’t air family business. You have to be strong. Turn to God.' These refrains (all of which I’ve heard at least once...) are just some of the responses that people dealing with mental health challenges in Latino communities have come to know well,” Ms. de León wrote. The unequal access to mental health services and health insurance that is a reality for some Latinos compounds the problem. The result is that mental illness can go untreated. Indeed, according to Ms. de León, Latinos, who are just as likely to suffer from a mental illness as non-Hispanic whites, are half as likely to seek treatment. Adriana Alejandre, a Latina who is a licensed marriage and family therapist in Los Angeles, is seeking to change that statistic. Through her podcast, Latinx Therapy, she seeks to spread the word that seeking therapy for mental illness is a positive step. There’s a long way to go, partly because Latino communities tend to value the group over the individual. “The downfall is that people suffer in silence,” said Ms. Alejandre. Therapy is important for some Latinos, according to Ms. Alejandre, because of intergenerational trauma that “allows the cycle to continue – whether it’s trauma, whether it’s depression, anxiety, domestic violence.” Ms. de León said one strategy she used for more than 1 year while she was in therapy was to set boundaries by not sharing what she was doing with family members. Ms. Alejandre said. “But the system will not change if someone does not initiate the change.” The New York Times.
Some state governments are seeking to make mental health services more available. The proposed budget of democratic Gov. Tony Evers of Wisconsin aims to allocate $22 million in mental health funding to school districts in the state to pay for social workers, psychologists, counselors, and nurses. The money would come on top of the $3 million designated by his predecessor and continues the efforts in Wisconsin to give children with mental health problems more access to needed help. The proposed budget also would add $7 million to a state program that works with local health agencies with the goal of providing mental health services for students and would allocate about $2.5 million annually for school staff training. The news is welcome to school districts across Wisconsin. “Schools are struggling to meet all of those [mental health] needs. I think there is an understanding that this is really something we need to be addressing,” said Joanne Juhnke, policy director at Wisconsin Family Ties, which helps families with children who have mental health challenges. Post Crescent, part of the USA Today network.
In Pennsylvania, the state Supreme Court is set to rule on whether those who provide mental health treatment to people addicted to illicit drugs can be free from prosecution. Right now, they are not. As reported in the Legal Intelligence, the case concerns two physicians at a drug addiction treatment facility who treated a man with an opioid addiction. In July 2018, a three-judge Superior Court panel upheld that physicians should not have liability protections under the Mental Health Procedures Act (MHPA). The ruling reversed a lower court decision. The Superior Court judges sympathized with the view that treatment of mental illness in drug treatment facilities be given more legal leeway. Whether that leeway remains in place depends on the Supreme Court. If judges decide no, physicians who recognize signs of mental illness in patients being treated for drug addiction would treat the illness at the risk of subsequent liability. The case has again raised the issue of whether alcoholism and drug dependency should be considered mental illnesses. “We don’t believe it was the intended purpose of the MPHA to include drug addiction. Our concern is we don’t want hospitals or rehab facilities just having patients be seen by psychiatrists in order to invoke the MHPA,” said Patrick Mintzer, the lawyer who will argue the cases before the court. A counter view came from Jack Panella, one of the three Superior Court judges. In his decision, he wrote: “In light of current scientific research, as well as the recent addition of ‘addiction disorders’ to the American Psychiatric Association’s Diagnostic and Statistical Manual–5, we suggest that the Department of Human Services revise this definition.” The Legal Intelligence.
An op-ed in the Des Moines Register applauds republican Gov. Kim Reynolds for introducing two bills that are aimed at expanding mental health services to children and family in Iowa. “After decades of discussion and growing public support, these two bills take a huge step toward establishing a children’s mental health system,” wrote guest columnists Erin Drinnin of the United Way of Central Iowa and Kim Scorza of Seasons Center for Behavioral Health. The two also serve as cochairs of the Coalition to Advance Mental Health in Iowa for Kids (CAMHI4Kids), which includes more than 50 organizations. “Just like building a house requires a sturdy foundation, these bills are an important first step toward creating a structure for children’s mental well-being. In particular, CAMHI4Kids appreciates that these bills establish a voice and a seat for children and families at a regional level, using a system that is already in place,” wrote Ms. Drinnin and Ms. Scorza. The legislation would spell out the core services that would be available regardless of location in Iowa. The services would be geared toward children, rather than adults, reflecting the different mental health needs of children. “These important steps would finally sew together a patchwork of care that families currently must navigate with little direction. If a child is hurt on the playground, a caregiver knows to follow a clear path of care to help that child recover. But for a caregiver who is concerned about a child’s mental health, they often don’t know where to turn for help and must seek out services that might not exist in their community,” wrote Ms. Drinnin and Ms. Scorza. In Iowa, 80,000 children have a diagnosed serious emotional disturbance. About half of children aged 14 years and older with mental illness drop out of high school, and 70% of youth in Iowa’s juvenile justice system have a mental illness. “We are proud that Iowa is working together in a bipartisan way to ensure that our kids have the best start for future success,” wrote Ms. Drinnin and Ms. Scorza. Des Moines Register.
Bill Reilly is the peer support program manager for Bert Nash Community Mental Health Center in Douglas County, Kan. His mental health troubles began in childhood and led to stints in alcohol rehabilitation and mental hospitals, and he tried to end his life several times. But Mr. Reilly now offers his experience to those in trouble. “Those [experiences] can be viewed as a negative until you turn that conversation around and ask, ‘How can this be helpful to another person?’ And to me, that’s where the urgency comes into the work that we’re doing because a clinical relationship is one thing, but a peer support relationship is something different.” He was speaking in support of an initiative that seeks to train and place peer support people in hospital emergency departments in Kansas. The initiative is being spearheaded by Bob Tryanski, Douglas County director of behavioral health projects. “In addition to giving folks the opportunity to have the work experience in an environment where we need peer support, we would wrap around those peers with training, professional development, with coaching and support in an ongoing way,” Mr. Tryanski said, “so that they could become real, robust, huge resources, not just to the emergency department but in our community.” If approved, hiring and training of peers would begin in April, with the goal of having six people in place in emergency rooms by the summer and hiring an additional six people by year end. LJWorld.com.
Intergenerational trauma, attitudes can allow cycles of depression, anxiety to continue
Intergenerational trauma, attitudes can allow cycles of depression, anxiety to continue
The stigma tied to mental illness can be particularly difficult to overcome for people of Latin American descent, writes Concepción de León in El Espace, a column in the New York Times focused on news and culture relevant to Latinx communities. Sometimes those seeking help run into familiar mantras. “Let me know if any of these sound familiar: 'Boys don’t cry. We don’t air family business. You have to be strong. Turn to God.' These refrains (all of which I’ve heard at least once...) are just some of the responses that people dealing with mental health challenges in Latino communities have come to know well,” Ms. de León wrote. The unequal access to mental health services and health insurance that is a reality for some Latinos compounds the problem. The result is that mental illness can go untreated. Indeed, according to Ms. de León, Latinos, who are just as likely to suffer from a mental illness as non-Hispanic whites, are half as likely to seek treatment. Adriana Alejandre, a Latina who is a licensed marriage and family therapist in Los Angeles, is seeking to change that statistic. Through her podcast, Latinx Therapy, she seeks to spread the word that seeking therapy for mental illness is a positive step. There’s a long way to go, partly because Latino communities tend to value the group over the individual. “The downfall is that people suffer in silence,” said Ms. Alejandre. Therapy is important for some Latinos, according to Ms. Alejandre, because of intergenerational trauma that “allows the cycle to continue – whether it’s trauma, whether it’s depression, anxiety, domestic violence.” Ms. de León said one strategy she used for more than 1 year while she was in therapy was to set boundaries by not sharing what she was doing with family members. Ms. Alejandre said. “But the system will not change if someone does not initiate the change.” The New York Times.
Some state governments are seeking to make mental health services more available. The proposed budget of democratic Gov. Tony Evers of Wisconsin aims to allocate $22 million in mental health funding to school districts in the state to pay for social workers, psychologists, counselors, and nurses. The money would come on top of the $3 million designated by his predecessor and continues the efforts in Wisconsin to give children with mental health problems more access to needed help. The proposed budget also would add $7 million to a state program that works with local health agencies with the goal of providing mental health services for students and would allocate about $2.5 million annually for school staff training. The news is welcome to school districts across Wisconsin. “Schools are struggling to meet all of those [mental health] needs. I think there is an understanding that this is really something we need to be addressing,” said Joanne Juhnke, policy director at Wisconsin Family Ties, which helps families with children who have mental health challenges. Post Crescent, part of the USA Today network.
In Pennsylvania, the state Supreme Court is set to rule on whether those who provide mental health treatment to people addicted to illicit drugs can be free from prosecution. Right now, they are not. As reported in the Legal Intelligence, the case concerns two physicians at a drug addiction treatment facility who treated a man with an opioid addiction. In July 2018, a three-judge Superior Court panel upheld that physicians should not have liability protections under the Mental Health Procedures Act (MHPA). The ruling reversed a lower court decision. The Superior Court judges sympathized with the view that treatment of mental illness in drug treatment facilities be given more legal leeway. Whether that leeway remains in place depends on the Supreme Court. If judges decide no, physicians who recognize signs of mental illness in patients being treated for drug addiction would treat the illness at the risk of subsequent liability. The case has again raised the issue of whether alcoholism and drug dependency should be considered mental illnesses. “We don’t believe it was the intended purpose of the MPHA to include drug addiction. Our concern is we don’t want hospitals or rehab facilities just having patients be seen by psychiatrists in order to invoke the MHPA,” said Patrick Mintzer, the lawyer who will argue the cases before the court. A counter view came from Jack Panella, one of the three Superior Court judges. In his decision, he wrote: “In light of current scientific research, as well as the recent addition of ‘addiction disorders’ to the American Psychiatric Association’s Diagnostic and Statistical Manual–5, we suggest that the Department of Human Services revise this definition.” The Legal Intelligence.
An op-ed in the Des Moines Register applauds republican Gov. Kim Reynolds for introducing two bills that are aimed at expanding mental health services to children and family in Iowa. “After decades of discussion and growing public support, these two bills take a huge step toward establishing a children’s mental health system,” wrote guest columnists Erin Drinnin of the United Way of Central Iowa and Kim Scorza of Seasons Center for Behavioral Health. The two also serve as cochairs of the Coalition to Advance Mental Health in Iowa for Kids (CAMHI4Kids), which includes more than 50 organizations. “Just like building a house requires a sturdy foundation, these bills are an important first step toward creating a structure for children’s mental well-being. In particular, CAMHI4Kids appreciates that these bills establish a voice and a seat for children and families at a regional level, using a system that is already in place,” wrote Ms. Drinnin and Ms. Scorza. The legislation would spell out the core services that would be available regardless of location in Iowa. The services would be geared toward children, rather than adults, reflecting the different mental health needs of children. “These important steps would finally sew together a patchwork of care that families currently must navigate with little direction. If a child is hurt on the playground, a caregiver knows to follow a clear path of care to help that child recover. But for a caregiver who is concerned about a child’s mental health, they often don’t know where to turn for help and must seek out services that might not exist in their community,” wrote Ms. Drinnin and Ms. Scorza. In Iowa, 80,000 children have a diagnosed serious emotional disturbance. About half of children aged 14 years and older with mental illness drop out of high school, and 70% of youth in Iowa’s juvenile justice system have a mental illness. “We are proud that Iowa is working together in a bipartisan way to ensure that our kids have the best start for future success,” wrote Ms. Drinnin and Ms. Scorza. Des Moines Register.
Bill Reilly is the peer support program manager for Bert Nash Community Mental Health Center in Douglas County, Kan. His mental health troubles began in childhood and led to stints in alcohol rehabilitation and mental hospitals, and he tried to end his life several times. But Mr. Reilly now offers his experience to those in trouble. “Those [experiences] can be viewed as a negative until you turn that conversation around and ask, ‘How can this be helpful to another person?’ And to me, that’s where the urgency comes into the work that we’re doing because a clinical relationship is one thing, but a peer support relationship is something different.” He was speaking in support of an initiative that seeks to train and place peer support people in hospital emergency departments in Kansas. The initiative is being spearheaded by Bob Tryanski, Douglas County director of behavioral health projects. “In addition to giving folks the opportunity to have the work experience in an environment where we need peer support, we would wrap around those peers with training, professional development, with coaching and support in an ongoing way,” Mr. Tryanski said, “so that they could become real, robust, huge resources, not just to the emergency department but in our community.” If approved, hiring and training of peers would begin in April, with the goal of having six people in place in emergency rooms by the summer and hiring an additional six people by year end. LJWorld.com.
The stigma tied to mental illness can be particularly difficult to overcome for people of Latin American descent, writes Concepción de León in El Espace, a column in the New York Times focused on news and culture relevant to Latinx communities. Sometimes those seeking help run into familiar mantras. “Let me know if any of these sound familiar: 'Boys don’t cry. We don’t air family business. You have to be strong. Turn to God.' These refrains (all of which I’ve heard at least once...) are just some of the responses that people dealing with mental health challenges in Latino communities have come to know well,” Ms. de León wrote. The unequal access to mental health services and health insurance that is a reality for some Latinos compounds the problem. The result is that mental illness can go untreated. Indeed, according to Ms. de León, Latinos, who are just as likely to suffer from a mental illness as non-Hispanic whites, are half as likely to seek treatment. Adriana Alejandre, a Latina who is a licensed marriage and family therapist in Los Angeles, is seeking to change that statistic. Through her podcast, Latinx Therapy, she seeks to spread the word that seeking therapy for mental illness is a positive step. There’s a long way to go, partly because Latino communities tend to value the group over the individual. “The downfall is that people suffer in silence,” said Ms. Alejandre. Therapy is important for some Latinos, according to Ms. Alejandre, because of intergenerational trauma that “allows the cycle to continue – whether it’s trauma, whether it’s depression, anxiety, domestic violence.” Ms. de León said one strategy she used for more than 1 year while she was in therapy was to set boundaries by not sharing what she was doing with family members. Ms. Alejandre said. “But the system will not change if someone does not initiate the change.” The New York Times.
Some state governments are seeking to make mental health services more available. The proposed budget of democratic Gov. Tony Evers of Wisconsin aims to allocate $22 million in mental health funding to school districts in the state to pay for social workers, psychologists, counselors, and nurses. The money would come on top of the $3 million designated by his predecessor and continues the efforts in Wisconsin to give children with mental health problems more access to needed help. The proposed budget also would add $7 million to a state program that works with local health agencies with the goal of providing mental health services for students and would allocate about $2.5 million annually for school staff training. The news is welcome to school districts across Wisconsin. “Schools are struggling to meet all of those [mental health] needs. I think there is an understanding that this is really something we need to be addressing,” said Joanne Juhnke, policy director at Wisconsin Family Ties, which helps families with children who have mental health challenges. Post Crescent, part of the USA Today network.
In Pennsylvania, the state Supreme Court is set to rule on whether those who provide mental health treatment to people addicted to illicit drugs can be free from prosecution. Right now, they are not. As reported in the Legal Intelligence, the case concerns two physicians at a drug addiction treatment facility who treated a man with an opioid addiction. In July 2018, a three-judge Superior Court panel upheld that physicians should not have liability protections under the Mental Health Procedures Act (MHPA). The ruling reversed a lower court decision. The Superior Court judges sympathized with the view that treatment of mental illness in drug treatment facilities be given more legal leeway. Whether that leeway remains in place depends on the Supreme Court. If judges decide no, physicians who recognize signs of mental illness in patients being treated for drug addiction would treat the illness at the risk of subsequent liability. The case has again raised the issue of whether alcoholism and drug dependency should be considered mental illnesses. “We don’t believe it was the intended purpose of the MPHA to include drug addiction. Our concern is we don’t want hospitals or rehab facilities just having patients be seen by psychiatrists in order to invoke the MHPA,” said Patrick Mintzer, the lawyer who will argue the cases before the court. A counter view came from Jack Panella, one of the three Superior Court judges. In his decision, he wrote: “In light of current scientific research, as well as the recent addition of ‘addiction disorders’ to the American Psychiatric Association’s Diagnostic and Statistical Manual–5, we suggest that the Department of Human Services revise this definition.” The Legal Intelligence.
An op-ed in the Des Moines Register applauds republican Gov. Kim Reynolds for introducing two bills that are aimed at expanding mental health services to children and family in Iowa. “After decades of discussion and growing public support, these two bills take a huge step toward establishing a children’s mental health system,” wrote guest columnists Erin Drinnin of the United Way of Central Iowa and Kim Scorza of Seasons Center for Behavioral Health. The two also serve as cochairs of the Coalition to Advance Mental Health in Iowa for Kids (CAMHI4Kids), which includes more than 50 organizations. “Just like building a house requires a sturdy foundation, these bills are an important first step toward creating a structure for children’s mental well-being. In particular, CAMHI4Kids appreciates that these bills establish a voice and a seat for children and families at a regional level, using a system that is already in place,” wrote Ms. Drinnin and Ms. Scorza. The legislation would spell out the core services that would be available regardless of location in Iowa. The services would be geared toward children, rather than adults, reflecting the different mental health needs of children. “These important steps would finally sew together a patchwork of care that families currently must navigate with little direction. If a child is hurt on the playground, a caregiver knows to follow a clear path of care to help that child recover. But for a caregiver who is concerned about a child’s mental health, they often don’t know where to turn for help and must seek out services that might not exist in their community,” wrote Ms. Drinnin and Ms. Scorza. In Iowa, 80,000 children have a diagnosed serious emotional disturbance. About half of children aged 14 years and older with mental illness drop out of high school, and 70% of youth in Iowa’s juvenile justice system have a mental illness. “We are proud that Iowa is working together in a bipartisan way to ensure that our kids have the best start for future success,” wrote Ms. Drinnin and Ms. Scorza. Des Moines Register.
Bill Reilly is the peer support program manager for Bert Nash Community Mental Health Center in Douglas County, Kan. His mental health troubles began in childhood and led to stints in alcohol rehabilitation and mental hospitals, and he tried to end his life several times. But Mr. Reilly now offers his experience to those in trouble. “Those [experiences] can be viewed as a negative until you turn that conversation around and ask, ‘How can this be helpful to another person?’ And to me, that’s where the urgency comes into the work that we’re doing because a clinical relationship is one thing, but a peer support relationship is something different.” He was speaking in support of an initiative that seeks to train and place peer support people in hospital emergency departments in Kansas. The initiative is being spearheaded by Bob Tryanski, Douglas County director of behavioral health projects. “In addition to giving folks the opportunity to have the work experience in an environment where we need peer support, we would wrap around those peers with training, professional development, with coaching and support in an ongoing way,” Mr. Tryanski said, “so that they could become real, robust, huge resources, not just to the emergency department but in our community.” If approved, hiring and training of peers would begin in April, with the goal of having six people in place in emergency rooms by the summer and hiring an additional six people by year end. LJWorld.com.