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Does incretin therapy increase pancreatic cancer risk?
Risk of pancreatic cancer doubled among diabetes patients on incretin therapy in a recent retrospective cohort study, although it is unlikely that the drugs actually caused the increase, according to investigators.
, wrote Dr. Mathieu Boniol, vice president of statistics, International Prevention Research Institute, Lyon, France, and colleagues.
The study was sparked by concerns about a possible increased risk of cancer among patients prescribed incretin drugs, which include glucagonlike peptide receptor–1 (GLP-1R) agonists and dipeptidyl peptidase 4 (DPP-4) inhibitors, authors said.
Results of the retrospective cohort analysis are based on two European public health insurance databases, comprising 33,292 diabetes patients treated with incretin drugs and 525,733 treated with other noninsulin antidiabetic drugs.
The risk of pancreatic cancer doubled for patients receiving incretin treatment (adjusted hazard ratio, 2.14; 95% confidence interval, 1.71-2.67), compared with patients receiving other noninsulin drugs, after adjusting for age, sex, and whether or not patients subsequently received an insulin prescription, investigators reported.
However, risk of pancreatic cancer decreased over time in patients on incretin therapy, according to further analyses by Dr. Boniol and colleagues.
That finding of diminishing risk over time argues against concluding that incretin drugs cause pancreatic cancer, according to investigators.
“A direct causal effect could be suspected if a steadily increasing risk of pancreatic cancer was associated with a steadily longer exposure to incretin drugs,” they said.
In the first 3 months after the first incretin prescription, risk of pancreatic cancer was 3.35 times greater (95% CI, 2.32-4.84), which “gradually diminished” to 1.69 (95% CI, 1.12-2.55) a year after the first prescription, the investigators said in the report.
As such, these new data do not help prove or disprove a causal link between incretin use and pancreatic cancer, continued Dr. Hellman, a past president of the American Association of Clinical Endocrinologists.
“I think, right now, we don’t have the data,” he said in an interview. “It’s a question that makes us nervous, because of what we know about the laboratory effects of the drugs, but we don’t have the answer yet. We need longer studies with larger numbers of people to answer that question.”
The study, funded by Sanofi, was conducted at the request of the European Medicines Agency to assess risk of pancreatic cancer associated with lixisenatide. However, the study covers a period prior to use of lixisenatide in the general population because the approval of the GLP-1R agonist was “too recent,” the study authors wrote.
The analyses in the study were conducted in 2015 and 2016 for two cohorts of subjects: one in Belgium, for which data had been collected from 2008 to 2013, and one in Italy, with data from 2000 to 2012.
Further studies are needed to assess how long-term use of incretin drugs may affect risk of pancreatic cancer, the authors said.
The analysis was conducted as part of a postauthorization safety study requested by the European Medicines Agency and funded by Sanofi. One study author reported receiving grants from Roche, Amgen, and Bristol-Myers Squibb outside the submitted work; the remaining investigators had no relevant financial disclosures.
Risk of pancreatic cancer doubled among diabetes patients on incretin therapy in a recent retrospective cohort study, although it is unlikely that the drugs actually caused the increase, according to investigators.
, wrote Dr. Mathieu Boniol, vice president of statistics, International Prevention Research Institute, Lyon, France, and colleagues.
The study was sparked by concerns about a possible increased risk of cancer among patients prescribed incretin drugs, which include glucagonlike peptide receptor–1 (GLP-1R) agonists and dipeptidyl peptidase 4 (DPP-4) inhibitors, authors said.
Results of the retrospective cohort analysis are based on two European public health insurance databases, comprising 33,292 diabetes patients treated with incretin drugs and 525,733 treated with other noninsulin antidiabetic drugs.
The risk of pancreatic cancer doubled for patients receiving incretin treatment (adjusted hazard ratio, 2.14; 95% confidence interval, 1.71-2.67), compared with patients receiving other noninsulin drugs, after adjusting for age, sex, and whether or not patients subsequently received an insulin prescription, investigators reported.
However, risk of pancreatic cancer decreased over time in patients on incretin therapy, according to further analyses by Dr. Boniol and colleagues.
That finding of diminishing risk over time argues against concluding that incretin drugs cause pancreatic cancer, according to investigators.
“A direct causal effect could be suspected if a steadily increasing risk of pancreatic cancer was associated with a steadily longer exposure to incretin drugs,” they said.
In the first 3 months after the first incretin prescription, risk of pancreatic cancer was 3.35 times greater (95% CI, 2.32-4.84), which “gradually diminished” to 1.69 (95% CI, 1.12-2.55) a year after the first prescription, the investigators said in the report.
As such, these new data do not help prove or disprove a causal link between incretin use and pancreatic cancer, continued Dr. Hellman, a past president of the American Association of Clinical Endocrinologists.
“I think, right now, we don’t have the data,” he said in an interview. “It’s a question that makes us nervous, because of what we know about the laboratory effects of the drugs, but we don’t have the answer yet. We need longer studies with larger numbers of people to answer that question.”
The study, funded by Sanofi, was conducted at the request of the European Medicines Agency to assess risk of pancreatic cancer associated with lixisenatide. However, the study covers a period prior to use of lixisenatide in the general population because the approval of the GLP-1R agonist was “too recent,” the study authors wrote.
The analyses in the study were conducted in 2015 and 2016 for two cohorts of subjects: one in Belgium, for which data had been collected from 2008 to 2013, and one in Italy, with data from 2000 to 2012.
Further studies are needed to assess how long-term use of incretin drugs may affect risk of pancreatic cancer, the authors said.
The analysis was conducted as part of a postauthorization safety study requested by the European Medicines Agency and funded by Sanofi. One study author reported receiving grants from Roche, Amgen, and Bristol-Myers Squibb outside the submitted work; the remaining investigators had no relevant financial disclosures.
Risk of pancreatic cancer doubled among diabetes patients on incretin therapy in a recent retrospective cohort study, although it is unlikely that the drugs actually caused the increase, according to investigators.
, wrote Dr. Mathieu Boniol, vice president of statistics, International Prevention Research Institute, Lyon, France, and colleagues.
The study was sparked by concerns about a possible increased risk of cancer among patients prescribed incretin drugs, which include glucagonlike peptide receptor–1 (GLP-1R) agonists and dipeptidyl peptidase 4 (DPP-4) inhibitors, authors said.
Results of the retrospective cohort analysis are based on two European public health insurance databases, comprising 33,292 diabetes patients treated with incretin drugs and 525,733 treated with other noninsulin antidiabetic drugs.
The risk of pancreatic cancer doubled for patients receiving incretin treatment (adjusted hazard ratio, 2.14; 95% confidence interval, 1.71-2.67), compared with patients receiving other noninsulin drugs, after adjusting for age, sex, and whether or not patients subsequently received an insulin prescription, investigators reported.
However, risk of pancreatic cancer decreased over time in patients on incretin therapy, according to further analyses by Dr. Boniol and colleagues.
That finding of diminishing risk over time argues against concluding that incretin drugs cause pancreatic cancer, according to investigators.
“A direct causal effect could be suspected if a steadily increasing risk of pancreatic cancer was associated with a steadily longer exposure to incretin drugs,” they said.
In the first 3 months after the first incretin prescription, risk of pancreatic cancer was 3.35 times greater (95% CI, 2.32-4.84), which “gradually diminished” to 1.69 (95% CI, 1.12-2.55) a year after the first prescription, the investigators said in the report.
As such, these new data do not help prove or disprove a causal link between incretin use and pancreatic cancer, continued Dr. Hellman, a past president of the American Association of Clinical Endocrinologists.
“I think, right now, we don’t have the data,” he said in an interview. “It’s a question that makes us nervous, because of what we know about the laboratory effects of the drugs, but we don’t have the answer yet. We need longer studies with larger numbers of people to answer that question.”
The study, funded by Sanofi, was conducted at the request of the European Medicines Agency to assess risk of pancreatic cancer associated with lixisenatide. However, the study covers a period prior to use of lixisenatide in the general population because the approval of the GLP-1R agonist was “too recent,” the study authors wrote.
The analyses in the study were conducted in 2015 and 2016 for two cohorts of subjects: one in Belgium, for which data had been collected from 2008 to 2013, and one in Italy, with data from 2000 to 2012.
Further studies are needed to assess how long-term use of incretin drugs may affect risk of pancreatic cancer, the authors said.
The analysis was conducted as part of a postauthorization safety study requested by the European Medicines Agency and funded by Sanofi. One study author reported receiving grants from Roche, Amgen, and Bristol-Myers Squibb outside the submitted work; the remaining investigators had no relevant financial disclosures.
FROM DIABETES CARE
Key clinical point: Incretin therapy was associated with increased pancreatic cancer risk, but possibly because of occult pancreatic cancer that aggravates diabetes.
Major finding: Patients receiving incretin drugs had a doubling of pancreatic cancer risk (aHR 2.14 (95% CI, 1.71-2.67).
Data source: Retrospective cohort analysis of public health insurance databases including 33,292 diabetes patients treated with incretin drugs and 525,733 treated with another noninsulin antidiabetic drug.
Disclosures: The analysis was conducted as part of a postauthorization safety study requested by the European Medicines Agency and funded by Sanofi. One study author reported receiving grants from Roche, Amgen, and Bristol-Myers Squibb outside the submitted work; the remaining investigators had no relevant financial disclosures.
Consider calcipotriol contact allergy when psoriasis doesn’t improve
Researchers at the University of Leuven (Belgium) conducted patch tests on six patients between 2004 and 2016 who presented with psoriasis that did not improve with use of topical calcipotriol.
Reports of contact allergy to calcipotriol are rare in the literature, considering its widespread use. However, the patch testing and successful alternative treatment confirmed the diagnosis of allergic contact dermatitis in all six cases.
“The lesions improved following replacement of calcipotriol therapy with topical corticosteroids and/or oral medication,” wrote An Goossens, MD, of the contact allergy unit in the department of dermatology at the university.
Five of the patients were adults ranging in age from 26 to 59 years (two men and three women), and the sixth was a 10-year-old girl. They all had lesions on their feet, scalp, or hands.
The successful patch test consisted of a 2 mcg/mL solution of calcipotriol in citrate-buffered isopropanol.
Patients who are diagnosed with this specific allergy may be able to tolerate treatment with a different topical vitamin D analog such as tacalcitol (Contact Derm. 2017 Nov. doi: 10.1111/cod.12910).
Researchers at the University of Leuven (Belgium) conducted patch tests on six patients between 2004 and 2016 who presented with psoriasis that did not improve with use of topical calcipotriol.
Reports of contact allergy to calcipotriol are rare in the literature, considering its widespread use. However, the patch testing and successful alternative treatment confirmed the diagnosis of allergic contact dermatitis in all six cases.
“The lesions improved following replacement of calcipotriol therapy with topical corticosteroids and/or oral medication,” wrote An Goossens, MD, of the contact allergy unit in the department of dermatology at the university.
Five of the patients were adults ranging in age from 26 to 59 years (two men and three women), and the sixth was a 10-year-old girl. They all had lesions on their feet, scalp, or hands.
The successful patch test consisted of a 2 mcg/mL solution of calcipotriol in citrate-buffered isopropanol.
Patients who are diagnosed with this specific allergy may be able to tolerate treatment with a different topical vitamin D analog such as tacalcitol (Contact Derm. 2017 Nov. doi: 10.1111/cod.12910).
Researchers at the University of Leuven (Belgium) conducted patch tests on six patients between 2004 and 2016 who presented with psoriasis that did not improve with use of topical calcipotriol.
Reports of contact allergy to calcipotriol are rare in the literature, considering its widespread use. However, the patch testing and successful alternative treatment confirmed the diagnosis of allergic contact dermatitis in all six cases.
“The lesions improved following replacement of calcipotriol therapy with topical corticosteroids and/or oral medication,” wrote An Goossens, MD, of the contact allergy unit in the department of dermatology at the university.
Five of the patients were adults ranging in age from 26 to 59 years (two men and three women), and the sixth was a 10-year-old girl. They all had lesions on their feet, scalp, or hands.
The successful patch test consisted of a 2 mcg/mL solution of calcipotriol in citrate-buffered isopropanol.
Patients who are diagnosed with this specific allergy may be able to tolerate treatment with a different topical vitamin D analog such as tacalcitol (Contact Derm. 2017 Nov. doi: 10.1111/cod.12910).
FROM CONTACT DERMATITIS
Tezacaftor-ivacaftor combo shows promise in cystic fibrosis
A new drug that targets the cystic fibrosis transmembrane conductance regulator protein could significantly improve lung function and other symptoms in patients with cystic fibrosis.
In a phase 3 double-blind, placebo controlled crossover trial, researchers examined the effects of tezacaftor – a cystic fibrosis transmembrane conductance regulator (CFTR) corrector – in combination with the CFTR potentiator ivacaftor, compared with ivacaftor alone or placebo.
“The addition of the CFTR corrector tezacaftor was hypothesized to enhance clinical benefit in patients with these mutations by increasing overall CFTR function,” wrote Dr. Steven M. Rowe of the division of pulmonary, allergy, and critical care medicine at the University of Alabama at Birmingham, and his coauthors. “This combination treatment is particularly important for restoring activity to those carrying two copies of the Phe508del CFTR mutation, as shown for the approved corrector-potentiator combination lumacaftor-ivacaftor, and may provide benefit to patients with other CFTR mutations.”
After two 8-week treatment periods in which patients were randomized to two of the three regimens, separated by an 8-week washout period, researchers saw significant improvements in predicted forced expiratory volume in 1 second (FEV1), both with tezacaftor-ivacaftor and ivacaftor alone, compared with placebo (N Engl J Med. 2017 Nov 23;377:2024-35. doi: 10.1056/NEJMoa1709847).
From baseline to the average of week 4 and 8, the combination of tezacaftor-ivacaftor was associated with a 6.8-percentage-point absolute change, and there was a 4.7-percentage-point improvement with ivacaftor alone compared with placebo. The difference between the tezacaftor-ivacaftor combination and ivacaftor monotherapy was also statistically significant in favor of the combination treatment.
Researchers also saw significant improvements in the secondary endpoint of absolute change in the Cystic Fibrosis Questionnaire–Revised score; the combination treatment was associated with an 11.1 point improvement compared with placebo, and monotherapy achieved a 9.7-point improvement. In the combination therapy group, 65% of patients achieved a clinically important difference of 4 points or greater, compared with 58% of patients in the monotherapy group and 33% of patients in the placebo group.
“These findings confirm the benefits of potentiator therapy in patients with residual CFTR function mutations and the added benefit conferred by corrector-potentiator combination therapy in this population,” the authors wrote.
The investigators also saw a lower rate of pulmonary exacerbations in the combined therapy group, but this did not reach statistical significance.
The rate of adverse events was similar across all three groups. Most were considered mild or moderate in severity and were largely clinical manifestations of cystic fibrosis.
Vertex Pharmaceuticals, which manufactures tezacaftor and ivacaftor, funded the study. Twelve of the thirteen authors reported receiving various kinds of support from Vertex, including personal fees, grant support, and nonfinancial support. Several authors reported ties to other industry sources.
This NEJM article came out with a companion article reporting phase 3 tezacaftor-ivacaftor results in homozygous CFTR Phe508del patients. Tezacaftor is a CFTR corrector developed by a company that has another corrector on the market, called lumacaftor. Lumacaftor is formulated with ivacaftor and available in the United States for patients age 6 and above who have two copies of Phe508del. It is exciting that another combination therapy has been developed that appears to be very effective and can be used for a second group of patients. This era of personalized medicine is extremely exciting, and we look forward to future therapies for all CFTR mutations.
This NEJM article came out with a companion article reporting phase 3 tezacaftor-ivacaftor results in homozygous CFTR Phe508del patients. Tezacaftor is a CFTR corrector developed by a company that has another corrector on the market, called lumacaftor. Lumacaftor is formulated with ivacaftor and available in the United States for patients age 6 and above who have two copies of Phe508del. It is exciting that another combination therapy has been developed that appears to be very effective and can be used for a second group of patients. This era of personalized medicine is extremely exciting, and we look forward to future therapies for all CFTR mutations.
This NEJM article came out with a companion article reporting phase 3 tezacaftor-ivacaftor results in homozygous CFTR Phe508del patients. Tezacaftor is a CFTR corrector developed by a company that has another corrector on the market, called lumacaftor. Lumacaftor is formulated with ivacaftor and available in the United States for patients age 6 and above who have two copies of Phe508del. It is exciting that another combination therapy has been developed that appears to be very effective and can be used for a second group of patients. This era of personalized medicine is extremely exciting, and we look forward to future therapies for all CFTR mutations.
A new drug that targets the cystic fibrosis transmembrane conductance regulator protein could significantly improve lung function and other symptoms in patients with cystic fibrosis.
In a phase 3 double-blind, placebo controlled crossover trial, researchers examined the effects of tezacaftor – a cystic fibrosis transmembrane conductance regulator (CFTR) corrector – in combination with the CFTR potentiator ivacaftor, compared with ivacaftor alone or placebo.
“The addition of the CFTR corrector tezacaftor was hypothesized to enhance clinical benefit in patients with these mutations by increasing overall CFTR function,” wrote Dr. Steven M. Rowe of the division of pulmonary, allergy, and critical care medicine at the University of Alabama at Birmingham, and his coauthors. “This combination treatment is particularly important for restoring activity to those carrying two copies of the Phe508del CFTR mutation, as shown for the approved corrector-potentiator combination lumacaftor-ivacaftor, and may provide benefit to patients with other CFTR mutations.”
After two 8-week treatment periods in which patients were randomized to two of the three regimens, separated by an 8-week washout period, researchers saw significant improvements in predicted forced expiratory volume in 1 second (FEV1), both with tezacaftor-ivacaftor and ivacaftor alone, compared with placebo (N Engl J Med. 2017 Nov 23;377:2024-35. doi: 10.1056/NEJMoa1709847).
From baseline to the average of week 4 and 8, the combination of tezacaftor-ivacaftor was associated with a 6.8-percentage-point absolute change, and there was a 4.7-percentage-point improvement with ivacaftor alone compared with placebo. The difference between the tezacaftor-ivacaftor combination and ivacaftor monotherapy was also statistically significant in favor of the combination treatment.
Researchers also saw significant improvements in the secondary endpoint of absolute change in the Cystic Fibrosis Questionnaire–Revised score; the combination treatment was associated with an 11.1 point improvement compared with placebo, and monotherapy achieved a 9.7-point improvement. In the combination therapy group, 65% of patients achieved a clinically important difference of 4 points or greater, compared with 58% of patients in the monotherapy group and 33% of patients in the placebo group.
“These findings confirm the benefits of potentiator therapy in patients with residual CFTR function mutations and the added benefit conferred by corrector-potentiator combination therapy in this population,” the authors wrote.
The investigators also saw a lower rate of pulmonary exacerbations in the combined therapy group, but this did not reach statistical significance.
The rate of adverse events was similar across all three groups. Most were considered mild or moderate in severity and were largely clinical manifestations of cystic fibrosis.
Vertex Pharmaceuticals, which manufactures tezacaftor and ivacaftor, funded the study. Twelve of the thirteen authors reported receiving various kinds of support from Vertex, including personal fees, grant support, and nonfinancial support. Several authors reported ties to other industry sources.
A new drug that targets the cystic fibrosis transmembrane conductance regulator protein could significantly improve lung function and other symptoms in patients with cystic fibrosis.
In a phase 3 double-blind, placebo controlled crossover trial, researchers examined the effects of tezacaftor – a cystic fibrosis transmembrane conductance regulator (CFTR) corrector – in combination with the CFTR potentiator ivacaftor, compared with ivacaftor alone or placebo.
“The addition of the CFTR corrector tezacaftor was hypothesized to enhance clinical benefit in patients with these mutations by increasing overall CFTR function,” wrote Dr. Steven M. Rowe of the division of pulmonary, allergy, and critical care medicine at the University of Alabama at Birmingham, and his coauthors. “This combination treatment is particularly important for restoring activity to those carrying two copies of the Phe508del CFTR mutation, as shown for the approved corrector-potentiator combination lumacaftor-ivacaftor, and may provide benefit to patients with other CFTR mutations.”
After two 8-week treatment periods in which patients were randomized to two of the three regimens, separated by an 8-week washout period, researchers saw significant improvements in predicted forced expiratory volume in 1 second (FEV1), both with tezacaftor-ivacaftor and ivacaftor alone, compared with placebo (N Engl J Med. 2017 Nov 23;377:2024-35. doi: 10.1056/NEJMoa1709847).
From baseline to the average of week 4 and 8, the combination of tezacaftor-ivacaftor was associated with a 6.8-percentage-point absolute change, and there was a 4.7-percentage-point improvement with ivacaftor alone compared with placebo. The difference between the tezacaftor-ivacaftor combination and ivacaftor monotherapy was also statistically significant in favor of the combination treatment.
Researchers also saw significant improvements in the secondary endpoint of absolute change in the Cystic Fibrosis Questionnaire–Revised score; the combination treatment was associated with an 11.1 point improvement compared with placebo, and monotherapy achieved a 9.7-point improvement. In the combination therapy group, 65% of patients achieved a clinically important difference of 4 points or greater, compared with 58% of patients in the monotherapy group and 33% of patients in the placebo group.
“These findings confirm the benefits of potentiator therapy in patients with residual CFTR function mutations and the added benefit conferred by corrector-potentiator combination therapy in this population,” the authors wrote.
The investigators also saw a lower rate of pulmonary exacerbations in the combined therapy group, but this did not reach statistical significance.
The rate of adverse events was similar across all three groups. Most were considered mild or moderate in severity and were largely clinical manifestations of cystic fibrosis.
Vertex Pharmaceuticals, which manufactures tezacaftor and ivacaftor, funded the study. Twelve of the thirteen authors reported receiving various kinds of support from Vertex, including personal fees, grant support, and nonfinancial support. Several authors reported ties to other industry sources.
FROM NEW ENGLAND JOURNAL OF MEDICINE
Key clinical point: The combination of tezacaftor and ivacaftor is associated with significant improvements in lung function in cystic fibrosis, compared with placebo or ivacaftor alone.
Major finding: Combined treatment with tezacaftor-ivacaftor was associated with a 6.8-percentage-point absolute change in FEV1 compared with placebo.
Data source: A phase 3 double-blind, placebo controlled, randomized crossover trial of 248 patients with cystic fibrosis.
Disclosures: Vertex Pharmaceuticals, which manufactures tezacaftor and ivacaftor, funded the study. Twelve of the thirteen authors reported receiving various kinds of support from Vertex, including personal fees, grant support, and nonfinancial support. Several authors reported ties to other industry sources.
Preventing substance use
Substance use disorders are affecting every pediatric practice as they are major contributors to morbidity and mortality in young people. With the ongoing risks of binge drinking, the current epidemic of opioid addiction and overdose deaths in the United States, and the shifting legal status and public perception of the risk of marijuana, how to deal with substance use disorders seems to be the focus of public conversation these days. , such as parent education and early recognition in pediatric practice.
Substance abuse risk
We cannot yet predict who can safely “experiment” with substances or who will develop dependency. However, there is information that we can use to identify those at greater risk. Youth who have a first-degree relative with a substance use disorder are at greater risk for developing such a disorder themselves, and this is especially so if there is a family history of alcoholism. Youth who suffer from a psychiatric illness, particularly from anxiety and mood disorders, have a special vulnerability to abusing substances, particularly when their underlying illness is untreated or incompletely treated. Youth with ADHD are at substantially elevated risk of developing substance use disorders, although there is a complex relationship between these two problems. The evidence currently suggests that for youth who began effective treatment prior to puberty, there is no elevation in risk, but for those who did not, there is a substantially elevated risk of substance use disorders. Finally, there has been research that indicates that children with a combination of sensation-seeking, high impulsivity, anxiety-sensitivity, and hopelessness are at the highest risk for substance use disorders.2
Prevention efforts you can make: To your patients
The first step in your prevention efforts is an open conversation about drugs and alcohol. Ask your middle schoolers about whether they have tried alcohol or any drugs. Have their friends? What are kids saying about alcohol? About marijuana? Vaping? Are there other substances that kids are talking about or trying? Be genuinely curious, warm, and nonjudgmental. Find out what they think the risks of these substances may be. If appropriate, offer them some education about known risks of substances to the developing brain, to school or athletic performance, and so on. You can teach them about other trusted resources, such as the National Institute on Drug Abuse (NIDA), which has a resource specifically for teens (teens.drugabuse.gov).
For your high school students and those heading off to college, provide a safe place to talk about what they have tried and whether they (or you) have any worries about substance use. You have a unique combination of clinical authority and expertise in them as individuals, and can help them meaningfully plan how to handle their choices. You might talk about the specific risks of binge drinking, from sexual assault to alcohol poisoning and permanent cognitive effects on their developing brains. They also can benefit from hearing about the actual risks of frequent marijuana use, including impaired cognitive performance (and permanent IQ decline), and ongoing risks to their still-developing brains. Don’t be surprised if your older adolescent patients want to educate you about risks. Be curious and humble, and don’t be afraid to go together to a third party for information. You should encourage their efforts to think critically, and be empathic to their dilemma as they try to balance risks against their drive to have new experiences, to be independent, and to be strongly connected to their peers.
Adolescents should hear about your concern about their specific risks with drugs and alcohol, such as a history of traumatic brain injury (concussion), a family history of drug or alcohol dependence, or their own diagnosis of anxiety, depression, or ADHD. You might point out that because they have not tried any drugs or alcohol in high school, they may be prone to having too much to drink when they first try it. Or you might observe that because they have an anxiety disorder, they are vulnerable to becoming dependent on alcohol. Hearing about their specific level of risk equips them to make wiser choices in the context of their growing autonomy.
Prevention efforts you can make: To the parents
Your other prevention strategies should include parents. Studies have shown that when parents have clear rules and expectations about drug and alcohol use, and are consistent about enforcing consequences in their home, their children are significantly less likely than their peers to have experimented with drugs or alcohol by their senior year in high school. Parents of children headed to middle school should hear about this fact, alongside accurate information about the risks associated with alcohol and specific drugs for the developing brain.
Finally, parents need to hear that they can be effective disciplinarians, while also making clear to their children that safety comes first, and that their rules should have clear exceptions for safety. If the parents have a rule against any use of alcohol or drugs, there should be an exception if their child is out and feels unsafe. If they are drunk, or their driver has been drinking, they can call for a ride and will not be in (much) trouble. Rules don’t have to be draconian to be effective; they should always support honesty and safety first. This is a lot of territory to cover, and you do not have to be the only resource for parents. Reliable online resources, such as NIDA’s and SAMHSA’s websites, are full of useful information, and others, such as teen-safe.org, have detailed resources for parents in particular.
References
1. Hum Genet. 2012 Jun;131(6):779-89.
2. Alcohol Clin Exp Res. 2013 Jan;37(Suppl 1):E281-90.
Dr. Swick is an attending psychiatrist in the division of child psychiatry at Massachusetts General Hospital, Boston, and director of the Parenting at a Challenging Time (PACT) Program at the Vernon Cancer Center at Newton Wellesley Hospital, also in Boston. Dr. Jellinek is professor emeritus of psychiatry and pediatrics, Harvard Medical School, Boston.
Substance use disorders are affecting every pediatric practice as they are major contributors to morbidity and mortality in young people. With the ongoing risks of binge drinking, the current epidemic of opioid addiction and overdose deaths in the United States, and the shifting legal status and public perception of the risk of marijuana, how to deal with substance use disorders seems to be the focus of public conversation these days. , such as parent education and early recognition in pediatric practice.
Substance abuse risk
We cannot yet predict who can safely “experiment” with substances or who will develop dependency. However, there is information that we can use to identify those at greater risk. Youth who have a first-degree relative with a substance use disorder are at greater risk for developing such a disorder themselves, and this is especially so if there is a family history of alcoholism. Youth who suffer from a psychiatric illness, particularly from anxiety and mood disorders, have a special vulnerability to abusing substances, particularly when their underlying illness is untreated or incompletely treated. Youth with ADHD are at substantially elevated risk of developing substance use disorders, although there is a complex relationship between these two problems. The evidence currently suggests that for youth who began effective treatment prior to puberty, there is no elevation in risk, but for those who did not, there is a substantially elevated risk of substance use disorders. Finally, there has been research that indicates that children with a combination of sensation-seeking, high impulsivity, anxiety-sensitivity, and hopelessness are at the highest risk for substance use disorders.2
Prevention efforts you can make: To your patients
The first step in your prevention efforts is an open conversation about drugs and alcohol. Ask your middle schoolers about whether they have tried alcohol or any drugs. Have their friends? What are kids saying about alcohol? About marijuana? Vaping? Are there other substances that kids are talking about or trying? Be genuinely curious, warm, and nonjudgmental. Find out what they think the risks of these substances may be. If appropriate, offer them some education about known risks of substances to the developing brain, to school or athletic performance, and so on. You can teach them about other trusted resources, such as the National Institute on Drug Abuse (NIDA), which has a resource specifically for teens (teens.drugabuse.gov).
For your high school students and those heading off to college, provide a safe place to talk about what they have tried and whether they (or you) have any worries about substance use. You have a unique combination of clinical authority and expertise in them as individuals, and can help them meaningfully plan how to handle their choices. You might talk about the specific risks of binge drinking, from sexual assault to alcohol poisoning and permanent cognitive effects on their developing brains. They also can benefit from hearing about the actual risks of frequent marijuana use, including impaired cognitive performance (and permanent IQ decline), and ongoing risks to their still-developing brains. Don’t be surprised if your older adolescent patients want to educate you about risks. Be curious and humble, and don’t be afraid to go together to a third party for information. You should encourage their efforts to think critically, and be empathic to their dilemma as they try to balance risks against their drive to have new experiences, to be independent, and to be strongly connected to their peers.
Adolescents should hear about your concern about their specific risks with drugs and alcohol, such as a history of traumatic brain injury (concussion), a family history of drug or alcohol dependence, or their own diagnosis of anxiety, depression, or ADHD. You might point out that because they have not tried any drugs or alcohol in high school, they may be prone to having too much to drink when they first try it. Or you might observe that because they have an anxiety disorder, they are vulnerable to becoming dependent on alcohol. Hearing about their specific level of risk equips them to make wiser choices in the context of their growing autonomy.
Prevention efforts you can make: To the parents
Your other prevention strategies should include parents. Studies have shown that when parents have clear rules and expectations about drug and alcohol use, and are consistent about enforcing consequences in their home, their children are significantly less likely than their peers to have experimented with drugs or alcohol by their senior year in high school. Parents of children headed to middle school should hear about this fact, alongside accurate information about the risks associated with alcohol and specific drugs for the developing brain.
Finally, parents need to hear that they can be effective disciplinarians, while also making clear to their children that safety comes first, and that their rules should have clear exceptions for safety. If the parents have a rule against any use of alcohol or drugs, there should be an exception if their child is out and feels unsafe. If they are drunk, or their driver has been drinking, they can call for a ride and will not be in (much) trouble. Rules don’t have to be draconian to be effective; they should always support honesty and safety first. This is a lot of territory to cover, and you do not have to be the only resource for parents. Reliable online resources, such as NIDA’s and SAMHSA’s websites, are full of useful information, and others, such as teen-safe.org, have detailed resources for parents in particular.
References
1. Hum Genet. 2012 Jun;131(6):779-89.
2. Alcohol Clin Exp Res. 2013 Jan;37(Suppl 1):E281-90.
Dr. Swick is an attending psychiatrist in the division of child psychiatry at Massachusetts General Hospital, Boston, and director of the Parenting at a Challenging Time (PACT) Program at the Vernon Cancer Center at Newton Wellesley Hospital, also in Boston. Dr. Jellinek is professor emeritus of psychiatry and pediatrics, Harvard Medical School, Boston.
Substance use disorders are affecting every pediatric practice as they are major contributors to morbidity and mortality in young people. With the ongoing risks of binge drinking, the current epidemic of opioid addiction and overdose deaths in the United States, and the shifting legal status and public perception of the risk of marijuana, how to deal with substance use disorders seems to be the focus of public conversation these days. , such as parent education and early recognition in pediatric practice.
Substance abuse risk
We cannot yet predict who can safely “experiment” with substances or who will develop dependency. However, there is information that we can use to identify those at greater risk. Youth who have a first-degree relative with a substance use disorder are at greater risk for developing such a disorder themselves, and this is especially so if there is a family history of alcoholism. Youth who suffer from a psychiatric illness, particularly from anxiety and mood disorders, have a special vulnerability to abusing substances, particularly when their underlying illness is untreated or incompletely treated. Youth with ADHD are at substantially elevated risk of developing substance use disorders, although there is a complex relationship between these two problems. The evidence currently suggests that for youth who began effective treatment prior to puberty, there is no elevation in risk, but for those who did not, there is a substantially elevated risk of substance use disorders. Finally, there has been research that indicates that children with a combination of sensation-seeking, high impulsivity, anxiety-sensitivity, and hopelessness are at the highest risk for substance use disorders.2
Prevention efforts you can make: To your patients
The first step in your prevention efforts is an open conversation about drugs and alcohol. Ask your middle schoolers about whether they have tried alcohol or any drugs. Have their friends? What are kids saying about alcohol? About marijuana? Vaping? Are there other substances that kids are talking about or trying? Be genuinely curious, warm, and nonjudgmental. Find out what they think the risks of these substances may be. If appropriate, offer them some education about known risks of substances to the developing brain, to school or athletic performance, and so on. You can teach them about other trusted resources, such as the National Institute on Drug Abuse (NIDA), which has a resource specifically for teens (teens.drugabuse.gov).
For your high school students and those heading off to college, provide a safe place to talk about what they have tried and whether they (or you) have any worries about substance use. You have a unique combination of clinical authority and expertise in them as individuals, and can help them meaningfully plan how to handle their choices. You might talk about the specific risks of binge drinking, from sexual assault to alcohol poisoning and permanent cognitive effects on their developing brains. They also can benefit from hearing about the actual risks of frequent marijuana use, including impaired cognitive performance (and permanent IQ decline), and ongoing risks to their still-developing brains. Don’t be surprised if your older adolescent patients want to educate you about risks. Be curious and humble, and don’t be afraid to go together to a third party for information. You should encourage their efforts to think critically, and be empathic to their dilemma as they try to balance risks against their drive to have new experiences, to be independent, and to be strongly connected to their peers.
Adolescents should hear about your concern about their specific risks with drugs and alcohol, such as a history of traumatic brain injury (concussion), a family history of drug or alcohol dependence, or their own diagnosis of anxiety, depression, or ADHD. You might point out that because they have not tried any drugs or alcohol in high school, they may be prone to having too much to drink when they first try it. Or you might observe that because they have an anxiety disorder, they are vulnerable to becoming dependent on alcohol. Hearing about their specific level of risk equips them to make wiser choices in the context of their growing autonomy.
Prevention efforts you can make: To the parents
Your other prevention strategies should include parents. Studies have shown that when parents have clear rules and expectations about drug and alcohol use, and are consistent about enforcing consequences in their home, their children are significantly less likely than their peers to have experimented with drugs or alcohol by their senior year in high school. Parents of children headed to middle school should hear about this fact, alongside accurate information about the risks associated with alcohol and specific drugs for the developing brain.
Finally, parents need to hear that they can be effective disciplinarians, while also making clear to their children that safety comes first, and that their rules should have clear exceptions for safety. If the parents have a rule against any use of alcohol or drugs, there should be an exception if their child is out and feels unsafe. If they are drunk, or their driver has been drinking, they can call for a ride and will not be in (much) trouble. Rules don’t have to be draconian to be effective; they should always support honesty and safety first. This is a lot of territory to cover, and you do not have to be the only resource for parents. Reliable online resources, such as NIDA’s and SAMHSA’s websites, are full of useful information, and others, such as teen-safe.org, have detailed resources for parents in particular.
References
1. Hum Genet. 2012 Jun;131(6):779-89.
2. Alcohol Clin Exp Res. 2013 Jan;37(Suppl 1):E281-90.
Dr. Swick is an attending psychiatrist in the division of child psychiatry at Massachusetts General Hospital, Boston, and director of the Parenting at a Challenging Time (PACT) Program at the Vernon Cancer Center at Newton Wellesley Hospital, also in Boston. Dr. Jellinek is professor emeritus of psychiatry and pediatrics, Harvard Medical School, Boston.
Interferon Beta May Reduce Mortality in MS
PARIS—Interferon beta is associated with a lower risk of all-cause mortality among patients with multiple sclerosis (MS) treated in clinical practice, according to data presented at the Seventh Joint ECTRIMS–ACTRIMS Meeting. Participants in the study were observed for as long as 18 years. The findings were consistent across two geographically distinct regions (ie, Canada and France), said the investigators.
Interferon beta has benefits for patients with MS, but whether the treatment prolongs survival in this population is unclear. Elaine Kingwell, PhD, a research associate in the Division of Neurology at the University of British Columbia in Vancouver, and colleagues investigated the association between interferon beta treatment and all-cause mortality in the clinical setting.
The researchers accessed prospectively collected data on patients with relapsing-remitting MS at onset, including sex, birth date, Expanded Disability Status Scale (EDSS) scores, and disease modifying treatments (DMTs), from British Columbia, Canada, and Rennes, France. Data were linked to population-based administrative databases capturing death dates in both countries. In Canada, data about drug prescriptions filled, universal health care registration, hospital admissions, and physician visits also were available. Patients were treatment-naïve at study entry, and investigators followed them from the earliest of first MS clinic visit, 18th birthday, or January 1, 1996, to the earliest of death, emigration, or December 31, 2013.
Using a nested case–control design, the researchers randomly selected as many as 20 MS controls by incidence density sampling and matched them to MS cases (ie, patients who died during follow-up) by sex, age (± 5 years), calendar year, and EDSS score at study entry. The association between all-cause mortality and interferon beta exposure (greater than six months) was estimated by conditional logistic regression, expressed as odds ratios (OR), and adjusted for glatiramer acetate (greater than six months exposure), any exposure to another DMT, age, and comorbidity burden. Analyses were stratified by sex and country. The researchers examined the association with cumulative exposure to interferon beta (up to three years or more than three years).
The cohort included 7,009 patients (75% women) with relapsing-remitting MS with a median age at study entry of 42. During follow-up (median, 12.3 years), 30% of participants were exposed to interferon beta, 11% were exposed to glatiramer acetate, and 12% were exposed to other DMTs, including MS-specific immunosuppressants. As many as 20 controls were successfully matched to each of 649 cases (mean age at death, 60). The odds of exposure to interferon beta was 32% lower among cases than controls. Stratification by sex or country did not change the interpretation of findings. Compared with no or minimal exposure, a longer cumulative time on interferon beta (ie, more than three years) was associated with increased survival (OR, 0.44), whereas exposure of less than three years was not (OR, 1.00).
PARIS—Interferon beta is associated with a lower risk of all-cause mortality among patients with multiple sclerosis (MS) treated in clinical practice, according to data presented at the Seventh Joint ECTRIMS–ACTRIMS Meeting. Participants in the study were observed for as long as 18 years. The findings were consistent across two geographically distinct regions (ie, Canada and France), said the investigators.
Interferon beta has benefits for patients with MS, but whether the treatment prolongs survival in this population is unclear. Elaine Kingwell, PhD, a research associate in the Division of Neurology at the University of British Columbia in Vancouver, and colleagues investigated the association between interferon beta treatment and all-cause mortality in the clinical setting.
The researchers accessed prospectively collected data on patients with relapsing-remitting MS at onset, including sex, birth date, Expanded Disability Status Scale (EDSS) scores, and disease modifying treatments (DMTs), from British Columbia, Canada, and Rennes, France. Data were linked to population-based administrative databases capturing death dates in both countries. In Canada, data about drug prescriptions filled, universal health care registration, hospital admissions, and physician visits also were available. Patients were treatment-naïve at study entry, and investigators followed them from the earliest of first MS clinic visit, 18th birthday, or January 1, 1996, to the earliest of death, emigration, or December 31, 2013.
Using a nested case–control design, the researchers randomly selected as many as 20 MS controls by incidence density sampling and matched them to MS cases (ie, patients who died during follow-up) by sex, age (± 5 years), calendar year, and EDSS score at study entry. The association between all-cause mortality and interferon beta exposure (greater than six months) was estimated by conditional logistic regression, expressed as odds ratios (OR), and adjusted for glatiramer acetate (greater than six months exposure), any exposure to another DMT, age, and comorbidity burden. Analyses were stratified by sex and country. The researchers examined the association with cumulative exposure to interferon beta (up to three years or more than three years).
The cohort included 7,009 patients (75% women) with relapsing-remitting MS with a median age at study entry of 42. During follow-up (median, 12.3 years), 30% of participants were exposed to interferon beta, 11% were exposed to glatiramer acetate, and 12% were exposed to other DMTs, including MS-specific immunosuppressants. As many as 20 controls were successfully matched to each of 649 cases (mean age at death, 60). The odds of exposure to interferon beta was 32% lower among cases than controls. Stratification by sex or country did not change the interpretation of findings. Compared with no or minimal exposure, a longer cumulative time on interferon beta (ie, more than three years) was associated with increased survival (OR, 0.44), whereas exposure of less than three years was not (OR, 1.00).
PARIS—Interferon beta is associated with a lower risk of all-cause mortality among patients with multiple sclerosis (MS) treated in clinical practice, according to data presented at the Seventh Joint ECTRIMS–ACTRIMS Meeting. Participants in the study were observed for as long as 18 years. The findings were consistent across two geographically distinct regions (ie, Canada and France), said the investigators.
Interferon beta has benefits for patients with MS, but whether the treatment prolongs survival in this population is unclear. Elaine Kingwell, PhD, a research associate in the Division of Neurology at the University of British Columbia in Vancouver, and colleagues investigated the association between interferon beta treatment and all-cause mortality in the clinical setting.
The researchers accessed prospectively collected data on patients with relapsing-remitting MS at onset, including sex, birth date, Expanded Disability Status Scale (EDSS) scores, and disease modifying treatments (DMTs), from British Columbia, Canada, and Rennes, France. Data were linked to population-based administrative databases capturing death dates in both countries. In Canada, data about drug prescriptions filled, universal health care registration, hospital admissions, and physician visits also were available. Patients were treatment-naïve at study entry, and investigators followed them from the earliest of first MS clinic visit, 18th birthday, or January 1, 1996, to the earliest of death, emigration, or December 31, 2013.
Using a nested case–control design, the researchers randomly selected as many as 20 MS controls by incidence density sampling and matched them to MS cases (ie, patients who died during follow-up) by sex, age (± 5 years), calendar year, and EDSS score at study entry. The association between all-cause mortality and interferon beta exposure (greater than six months) was estimated by conditional logistic regression, expressed as odds ratios (OR), and adjusted for glatiramer acetate (greater than six months exposure), any exposure to another DMT, age, and comorbidity burden. Analyses were stratified by sex and country. The researchers examined the association with cumulative exposure to interferon beta (up to three years or more than three years).
The cohort included 7,009 patients (75% women) with relapsing-remitting MS with a median age at study entry of 42. During follow-up (median, 12.3 years), 30% of participants were exposed to interferon beta, 11% were exposed to glatiramer acetate, and 12% were exposed to other DMTs, including MS-specific immunosuppressants. As many as 20 controls were successfully matched to each of 649 cases (mean age at death, 60). The odds of exposure to interferon beta was 32% lower among cases than controls. Stratification by sex or country did not change the interpretation of findings. Compared with no or minimal exposure, a longer cumulative time on interferon beta (ie, more than three years) was associated with increased survival (OR, 0.44), whereas exposure of less than three years was not (OR, 1.00).
More to psychiatry than just neuroscience; The impact of childhood trauma
More to psychiatry than just neuroscience
In his editorial “Advancing clinical neuroscience literacy among psychiatric practitioners” (From the Editor,
I find that many of my patients look for more or different drugs to fix their dysfunctional patterns in life—many of which stem from their dysfunctional and traumatic childhoods. Thus, it is more than just drugs and neurochemical pathways, more than just the “dysregulated neural circuitry,” that we need to focus on in our psychiatric practice.
I finished my psychiatric residency in 1972, before we knew much about neuroscience. Since then, we have learned so much about neuroscience and the specific neuroscience mechanisms involved in the brain and mind. Those advances have done much to aid our core understanding of psychiatric disorders. However, let us not forget that there is more to the mind than just neurochemistry, and more to our practice of psychiatry than just neuroscience.
Leonard Korn, MD
Psychiatrist
Portsmouth Regional Hospital
Portsmouth, New Hampshire
Dr. Nasrallah responds
It is now widely accepted in our field that all psychological phenomena and all human behaviors are associated with neurobiological components. All life events, especially traumatic experiences, are transduced into structural and chemical changes, often within minutes. The formation of dendritic spines to encode the memory of one’s experiences throughout waking hours is well established in neuroscience, and hundreds of studies have been published about this.
Psychotherapy is a neurobiological intervention that induces neuroplasticity and leads to structural brain repair, because talking, listening, triggering memories, inducing insight, and “connecting the dots” in one’s behavior are all biological events.1,2 There is no such thing as a purely psychological process independent of the brain. The mind is the product of ongoing complex, intricate activity of brain neurocircuits whose neurobiological activity is translated into thoughts, emotions, impulses, and behaviors. The mind is perpetually tethered to its neurological roots.
Thus, reductionism actually describes a scientific fact and is not a term with pejorative connotations used to shut down scientific discourse about the biological basis of human behavior. By advancing their clinical neuroscience literacy, psychiatric practitioners will understand that they deal with a specific brain pathology in every patient that they treat and that the medications and psychotherapeutic interventions they employ are synergistic biological treatments.3
Henry A. Nasrallah, MD
Professor and Chair
Department of Psychiatry and Behavioral Neuroscience
Saint Louis University School of Medicine
St. Louis, Missouri
References
1. Nasrallah HA. Repositioning psychotherapy as a neurobiological intervention. Current Psychiatry. 2013;12(12):18-19.
2. Nasrallah HA. Out-of-the-box questions about psychotherapy. Current Psychiatry. 2010;9(10):13-14.
3. Nasrallah HA. Medications with psychotherapy: a synergy to heal the brain. C urrent Psychiatry. 2006;5(10):11-12.
The impact of childhood trauma
I enjoyed Dr. Nasrallah’s article “Beyond DSM-5: Clinical and biologic features shared by major psychiatric syndromes” (From the Editor, Current Psychiatry. October 2017, p. 4,6-7), but there was only 1 mention of childhood trauma, which shares features with most of the commonalities he described, such as inflammation, smaller brain volumes, gene and environment interaction, shortened telomeres, and elevated cortisol levels. The Adverse Childhood Experiences Study1 taught us about the impact of childhood trauma on the entire organism. We need to focus on that commonality.
Susan Jones, MD
Child and Adolescent Psychiatrist
Virginia Treatment Center for Children
Assistant Professor
Virginia Commonwealth University
School of Medicine
Richmond, Virginia
Reference
1. Felitti VJ, Anda RF, Nordenberg D, et al. Relationship of childhood abuse and household dysfunction to many of the leading causes of death in adults. The Adverse Childhood Experiences (ACE) Study. Am J Prev Med. 1998;14(4):245-258
Dr. Nasrallah responds
It is worth pointing out that childhood trauma predominantly leads to psychotic and mood disorders in adulthood, and the criteria I mentioned would then hold true.
More to psychiatry than just neuroscience
In his editorial “Advancing clinical neuroscience literacy among psychiatric practitioners” (From the Editor,
I find that many of my patients look for more or different drugs to fix their dysfunctional patterns in life—many of which stem from their dysfunctional and traumatic childhoods. Thus, it is more than just drugs and neurochemical pathways, more than just the “dysregulated neural circuitry,” that we need to focus on in our psychiatric practice.
I finished my psychiatric residency in 1972, before we knew much about neuroscience. Since then, we have learned so much about neuroscience and the specific neuroscience mechanisms involved in the brain and mind. Those advances have done much to aid our core understanding of psychiatric disorders. However, let us not forget that there is more to the mind than just neurochemistry, and more to our practice of psychiatry than just neuroscience.
Leonard Korn, MD
Psychiatrist
Portsmouth Regional Hospital
Portsmouth, New Hampshire
Dr. Nasrallah responds
It is now widely accepted in our field that all psychological phenomena and all human behaviors are associated with neurobiological components. All life events, especially traumatic experiences, are transduced into structural and chemical changes, often within minutes. The formation of dendritic spines to encode the memory of one’s experiences throughout waking hours is well established in neuroscience, and hundreds of studies have been published about this.
Psychotherapy is a neurobiological intervention that induces neuroplasticity and leads to structural brain repair, because talking, listening, triggering memories, inducing insight, and “connecting the dots” in one’s behavior are all biological events.1,2 There is no such thing as a purely psychological process independent of the brain. The mind is the product of ongoing complex, intricate activity of brain neurocircuits whose neurobiological activity is translated into thoughts, emotions, impulses, and behaviors. The mind is perpetually tethered to its neurological roots.
Thus, reductionism actually describes a scientific fact and is not a term with pejorative connotations used to shut down scientific discourse about the biological basis of human behavior. By advancing their clinical neuroscience literacy, psychiatric practitioners will understand that they deal with a specific brain pathology in every patient that they treat and that the medications and psychotherapeutic interventions they employ are synergistic biological treatments.3
Henry A. Nasrallah, MD
Professor and Chair
Department of Psychiatry and Behavioral Neuroscience
Saint Louis University School of Medicine
St. Louis, Missouri
References
1. Nasrallah HA. Repositioning psychotherapy as a neurobiological intervention. Current Psychiatry. 2013;12(12):18-19.
2. Nasrallah HA. Out-of-the-box questions about psychotherapy. Current Psychiatry. 2010;9(10):13-14.
3. Nasrallah HA. Medications with psychotherapy: a synergy to heal the brain. C urrent Psychiatry. 2006;5(10):11-12.
The impact of childhood trauma
I enjoyed Dr. Nasrallah’s article “Beyond DSM-5: Clinical and biologic features shared by major psychiatric syndromes” (From the Editor, Current Psychiatry. October 2017, p. 4,6-7), but there was only 1 mention of childhood trauma, which shares features with most of the commonalities he described, such as inflammation, smaller brain volumes, gene and environment interaction, shortened telomeres, and elevated cortisol levels. The Adverse Childhood Experiences Study1 taught us about the impact of childhood trauma on the entire organism. We need to focus on that commonality.
Susan Jones, MD
Child and Adolescent Psychiatrist
Virginia Treatment Center for Children
Assistant Professor
Virginia Commonwealth University
School of Medicine
Richmond, Virginia
Reference
1. Felitti VJ, Anda RF, Nordenberg D, et al. Relationship of childhood abuse and household dysfunction to many of the leading causes of death in adults. The Adverse Childhood Experiences (ACE) Study. Am J Prev Med. 1998;14(4):245-258
Dr. Nasrallah responds
It is worth pointing out that childhood trauma predominantly leads to psychotic and mood disorders in adulthood, and the criteria I mentioned would then hold true.
More to psychiatry than just neuroscience
In his editorial “Advancing clinical neuroscience literacy among psychiatric practitioners” (From the Editor,
I find that many of my patients look for more or different drugs to fix their dysfunctional patterns in life—many of which stem from their dysfunctional and traumatic childhoods. Thus, it is more than just drugs and neurochemical pathways, more than just the “dysregulated neural circuitry,” that we need to focus on in our psychiatric practice.
I finished my psychiatric residency in 1972, before we knew much about neuroscience. Since then, we have learned so much about neuroscience and the specific neuroscience mechanisms involved in the brain and mind. Those advances have done much to aid our core understanding of psychiatric disorders. However, let us not forget that there is more to the mind than just neurochemistry, and more to our practice of psychiatry than just neuroscience.
Leonard Korn, MD
Psychiatrist
Portsmouth Regional Hospital
Portsmouth, New Hampshire
Dr. Nasrallah responds
It is now widely accepted in our field that all psychological phenomena and all human behaviors are associated with neurobiological components. All life events, especially traumatic experiences, are transduced into structural and chemical changes, often within minutes. The formation of dendritic spines to encode the memory of one’s experiences throughout waking hours is well established in neuroscience, and hundreds of studies have been published about this.
Psychotherapy is a neurobiological intervention that induces neuroplasticity and leads to structural brain repair, because talking, listening, triggering memories, inducing insight, and “connecting the dots” in one’s behavior are all biological events.1,2 There is no such thing as a purely psychological process independent of the brain. The mind is the product of ongoing complex, intricate activity of brain neurocircuits whose neurobiological activity is translated into thoughts, emotions, impulses, and behaviors. The mind is perpetually tethered to its neurological roots.
Thus, reductionism actually describes a scientific fact and is not a term with pejorative connotations used to shut down scientific discourse about the biological basis of human behavior. By advancing their clinical neuroscience literacy, psychiatric practitioners will understand that they deal with a specific brain pathology in every patient that they treat and that the medications and psychotherapeutic interventions they employ are synergistic biological treatments.3
Henry A. Nasrallah, MD
Professor and Chair
Department of Psychiatry and Behavioral Neuroscience
Saint Louis University School of Medicine
St. Louis, Missouri
References
1. Nasrallah HA. Repositioning psychotherapy as a neurobiological intervention. Current Psychiatry. 2013;12(12):18-19.
2. Nasrallah HA. Out-of-the-box questions about psychotherapy. Current Psychiatry. 2010;9(10):13-14.
3. Nasrallah HA. Medications with psychotherapy: a synergy to heal the brain. C urrent Psychiatry. 2006;5(10):11-12.
The impact of childhood trauma
I enjoyed Dr. Nasrallah’s article “Beyond DSM-5: Clinical and biologic features shared by major psychiatric syndromes” (From the Editor, Current Psychiatry. October 2017, p. 4,6-7), but there was only 1 mention of childhood trauma, which shares features with most of the commonalities he described, such as inflammation, smaller brain volumes, gene and environment interaction, shortened telomeres, and elevated cortisol levels. The Adverse Childhood Experiences Study1 taught us about the impact of childhood trauma on the entire organism. We need to focus on that commonality.
Susan Jones, MD
Child and Adolescent Psychiatrist
Virginia Treatment Center for Children
Assistant Professor
Virginia Commonwealth University
School of Medicine
Richmond, Virginia
Reference
1. Felitti VJ, Anda RF, Nordenberg D, et al. Relationship of childhood abuse and household dysfunction to many of the leading causes of death in adults. The Adverse Childhood Experiences (ACE) Study. Am J Prev Med. 1998;14(4):245-258
Dr. Nasrallah responds
It is worth pointing out that childhood trauma predominantly leads to psychotic and mood disorders in adulthood, and the criteria I mentioned would then hold true.
FDA grants orphan drug status to rofecoxib for hemophilic arthropathy
The Food and Drug Administration on Nov. 21 granted orphan drug designation to rofecoxib (TRM-201), a cyclooxygenase 2–selective nonsteroidal anti-inflammatory drug (NSAID) intended to treat patients with hemophilic arthropathy (HA).
HA, a joint disease caused by hemarthrosis, is the largest cause of morbidity for hemophilia patients. There are currently no approved treatments in the United States.
The attempt at a reintroduction of rofecoxib specifically for the treatment of HA is being developed by Tremeau Pharmaceuticals.
Patients with hemophilia look to avoid traditional NSAIDs, as those drugs risk gastrointestinal ulcers and impair platelet aggregation. The current standard of care for HA is opioid treatment.
Rofecoxib and other NSAIDs cause an increased risk of serious cardiovascular thrombotic events and gastrointestinal adverse events.
Orphan drug status is available to treatments for rare disorders and provides a 7-year marketing exclusivity period against competition, along with tax credits and a waiver of Prescription Drug User Fee Act filing fees.
The Food and Drug Administration on Nov. 21 granted orphan drug designation to rofecoxib (TRM-201), a cyclooxygenase 2–selective nonsteroidal anti-inflammatory drug (NSAID) intended to treat patients with hemophilic arthropathy (HA).
HA, a joint disease caused by hemarthrosis, is the largest cause of morbidity for hemophilia patients. There are currently no approved treatments in the United States.
The attempt at a reintroduction of rofecoxib specifically for the treatment of HA is being developed by Tremeau Pharmaceuticals.
Patients with hemophilia look to avoid traditional NSAIDs, as those drugs risk gastrointestinal ulcers and impair platelet aggregation. The current standard of care for HA is opioid treatment.
Rofecoxib and other NSAIDs cause an increased risk of serious cardiovascular thrombotic events and gastrointestinal adverse events.
Orphan drug status is available to treatments for rare disorders and provides a 7-year marketing exclusivity period against competition, along with tax credits and a waiver of Prescription Drug User Fee Act filing fees.
The Food and Drug Administration on Nov. 21 granted orphan drug designation to rofecoxib (TRM-201), a cyclooxygenase 2–selective nonsteroidal anti-inflammatory drug (NSAID) intended to treat patients with hemophilic arthropathy (HA).
HA, a joint disease caused by hemarthrosis, is the largest cause of morbidity for hemophilia patients. There are currently no approved treatments in the United States.
The attempt at a reintroduction of rofecoxib specifically for the treatment of HA is being developed by Tremeau Pharmaceuticals.
Patients with hemophilia look to avoid traditional NSAIDs, as those drugs risk gastrointestinal ulcers and impair platelet aggregation. The current standard of care for HA is opioid treatment.
Rofecoxib and other NSAIDs cause an increased risk of serious cardiovascular thrombotic events and gastrointestinal adverse events.
Orphan drug status is available to treatments for rare disorders and provides a 7-year marketing exclusivity period against competition, along with tax credits and a waiver of Prescription Drug User Fee Act filing fees.
Siponimod Improves MRI Outcomes in Patients With Secondary Progressive MS
PARIS—Siponimod significantly reduces MRI activity and slows brain volume loss in patients with secondary progressive multiple sclerosis (MS), according to a study described at the Seventh Joint ECTRIMS–ACTRIMS Meeting. Effects are observable at month 12 and sustained at month 24. “These results, together with the clinically observed reduction in confirmed disability progression reported previously, corroborate the positive impact of treatment with siponimod in patients with secondary progressive MS,” said Robert Fox, MD, a researcher at the Mellen Center for Treatment and Research in MS in the Cleveland Clinic, and colleagues.
The EXPAND study demonstrated the benefits of siponimod, a selective modulator of sphingosine 1-phosphate receptor subtypes 1 and 5, on confirmed disability progression. Dr. Fox and colleagues examined these data to evaluate the effect of siponimod versus placebo on predefined MRI outcomes in patients with secondary progressive MS.
The researchers randomized patients 2:1 to receive siponimod or placebo. MRI scans were performed at baseline and every 12 months thereafter. Radiologists at a central reading center analyzed the scans. Key MRI outcomes included T2 lesion volume, number of new or enlarging T2 lesions, number of gadolinium-enhancing lesions, and brain volume loss assessed by percent brain volume change.
The full analysis set comprised patients who received one or more doses of study drug as per original randomization. The per-protocol analysis set consisted of all full-analysis-set patients without major protocol deviations and included efficacy data only up to discontinuation of double-blinded treatment.
The investigators randomized 1,651 patients. A total of 1,099 patients received siponimod (2 mg), and 546 received placebo. Dr. Fox and colleagues observed treatment benefits in favor of siponimod for all key outcomes and analysis sets investigated. Post-baseline MRI data were available for more than 80% of participants.
At month 12, the adjusted mean differences in the change in T2 lesion volume from baseline versus placebo were −613 mm3 in the full analysis set and −634 mm3 in the per protocol analysis set. At month 24, the differences were −778 mm3 in the full analysis set and −830 mm3 in the per protocol analysis set.
At month 12, the adjusted mean differences in percent brain volume change were 0.175 in the full analysis set and 0.221 in the per protocol analysis set. At month 24, the differences were 0.128 in the full analysis set and 0.277 in the per protocol analysis set.
Siponimod reduced the average T1 gadolinium-enhancing lesion count over months 12 and 24 by 86.6% in the full analysis set and 91.1% in the per protocol analysis set. Siponimod reduced the average count of new or enlarging T2 lesions by 80.6% in the full analysis set and 85.3% in the per protocol analysis set.
This study was funded by Novartis Pharma, which is headquartered in Basel, Switzerland.
PARIS—Siponimod significantly reduces MRI activity and slows brain volume loss in patients with secondary progressive multiple sclerosis (MS), according to a study described at the Seventh Joint ECTRIMS–ACTRIMS Meeting. Effects are observable at month 12 and sustained at month 24. “These results, together with the clinically observed reduction in confirmed disability progression reported previously, corroborate the positive impact of treatment with siponimod in patients with secondary progressive MS,” said Robert Fox, MD, a researcher at the Mellen Center for Treatment and Research in MS in the Cleveland Clinic, and colleagues.
The EXPAND study demonstrated the benefits of siponimod, a selective modulator of sphingosine 1-phosphate receptor subtypes 1 and 5, on confirmed disability progression. Dr. Fox and colleagues examined these data to evaluate the effect of siponimod versus placebo on predefined MRI outcomes in patients with secondary progressive MS.
The researchers randomized patients 2:1 to receive siponimod or placebo. MRI scans were performed at baseline and every 12 months thereafter. Radiologists at a central reading center analyzed the scans. Key MRI outcomes included T2 lesion volume, number of new or enlarging T2 lesions, number of gadolinium-enhancing lesions, and brain volume loss assessed by percent brain volume change.
The full analysis set comprised patients who received one or more doses of study drug as per original randomization. The per-protocol analysis set consisted of all full-analysis-set patients without major protocol deviations and included efficacy data only up to discontinuation of double-blinded treatment.
The investigators randomized 1,651 patients. A total of 1,099 patients received siponimod (2 mg), and 546 received placebo. Dr. Fox and colleagues observed treatment benefits in favor of siponimod for all key outcomes and analysis sets investigated. Post-baseline MRI data were available for more than 80% of participants.
At month 12, the adjusted mean differences in the change in T2 lesion volume from baseline versus placebo were −613 mm3 in the full analysis set and −634 mm3 in the per protocol analysis set. At month 24, the differences were −778 mm3 in the full analysis set and −830 mm3 in the per protocol analysis set.
At month 12, the adjusted mean differences in percent brain volume change were 0.175 in the full analysis set and 0.221 in the per protocol analysis set. At month 24, the differences were 0.128 in the full analysis set and 0.277 in the per protocol analysis set.
Siponimod reduced the average T1 gadolinium-enhancing lesion count over months 12 and 24 by 86.6% in the full analysis set and 91.1% in the per protocol analysis set. Siponimod reduced the average count of new or enlarging T2 lesions by 80.6% in the full analysis set and 85.3% in the per protocol analysis set.
This study was funded by Novartis Pharma, which is headquartered in Basel, Switzerland.
PARIS—Siponimod significantly reduces MRI activity and slows brain volume loss in patients with secondary progressive multiple sclerosis (MS), according to a study described at the Seventh Joint ECTRIMS–ACTRIMS Meeting. Effects are observable at month 12 and sustained at month 24. “These results, together with the clinically observed reduction in confirmed disability progression reported previously, corroborate the positive impact of treatment with siponimod in patients with secondary progressive MS,” said Robert Fox, MD, a researcher at the Mellen Center for Treatment and Research in MS in the Cleveland Clinic, and colleagues.
The EXPAND study demonstrated the benefits of siponimod, a selective modulator of sphingosine 1-phosphate receptor subtypes 1 and 5, on confirmed disability progression. Dr. Fox and colleagues examined these data to evaluate the effect of siponimod versus placebo on predefined MRI outcomes in patients with secondary progressive MS.
The researchers randomized patients 2:1 to receive siponimod or placebo. MRI scans were performed at baseline and every 12 months thereafter. Radiologists at a central reading center analyzed the scans. Key MRI outcomes included T2 lesion volume, number of new or enlarging T2 lesions, number of gadolinium-enhancing lesions, and brain volume loss assessed by percent brain volume change.
The full analysis set comprised patients who received one or more doses of study drug as per original randomization. The per-protocol analysis set consisted of all full-analysis-set patients without major protocol deviations and included efficacy data only up to discontinuation of double-blinded treatment.
The investigators randomized 1,651 patients. A total of 1,099 patients received siponimod (2 mg), and 546 received placebo. Dr. Fox and colleagues observed treatment benefits in favor of siponimod for all key outcomes and analysis sets investigated. Post-baseline MRI data were available for more than 80% of participants.
At month 12, the adjusted mean differences in the change in T2 lesion volume from baseline versus placebo were −613 mm3 in the full analysis set and −634 mm3 in the per protocol analysis set. At month 24, the differences were −778 mm3 in the full analysis set and −830 mm3 in the per protocol analysis set.
At month 12, the adjusted mean differences in percent brain volume change were 0.175 in the full analysis set and 0.221 in the per protocol analysis set. At month 24, the differences were 0.128 in the full analysis set and 0.277 in the per protocol analysis set.
Siponimod reduced the average T1 gadolinium-enhancing lesion count over months 12 and 24 by 86.6% in the full analysis set and 91.1% in the per protocol analysis set. Siponimod reduced the average count of new or enlarging T2 lesions by 80.6% in the full analysis set and 85.3% in the per protocol analysis set.
This study was funded by Novartis Pharma, which is headquartered in Basel, Switzerland.
REBOA improves survival for trauma patients
SCOTTSDALE, ARIZ. – In a small, single-center study of patients with subdiaphragmatic hemorrhage, resuscitative endovascular balloon occlusion of the aorta (REBOA) improved hemodynamic status and 30-day survival rates, compared with resuscitative thoracotomy (RT).
Although the technique was first developed during the Korean War, REBOA never really caught on, possibly because of limitations in endovascular technology. But recent advances in surgical technique have revitalized interest.
Despite the success of the study, some audience members expressed concerns about the skill set required. One questioner pointed out that emergency department physicians may be tempted to use the technique, even though they may not possess the requisite catheter and wire skills. That is a legitimate concern, according to senior author R. Stephen Smith, MD, FACS, professor of acute care surgery at the University of Florida, Gainesville. But this is already happening, he said. “They’ve already done it in the field in Britain, and most are placed by nonsurgeons in Japan. Frankly, we need to pay particular attention to the skills of those emergency medicine physicians, because the average emergency medicine physician at this point really doesn’t have the catheter or wire-based skills to do this safely,” Dr. Smith said at the annual meeting of the Western Surgical Association.
The researchers examined outcomes in patients who underwent REBOA versus RT over a 21-month (2015-2017) period at their institution. Before adopting REBOA, attending surgeons and senior surgical residents attended a 1.5-hour slide presentation combined with simulation training. No external course was required. Operating room personnel received a 30-minute slide presentation. The procedures were conducted in a dedicated trauma operating room equipped with imaging.
Sixteen patients underwent REBOA during the study period, with a mean injury severity score of 38.6. Preoperative hemoglobin levels ranged from 5 to 14.4 mg/dL, and the majority were acidotic because of trauma.
Fourteen of the 16 patients who underwent REBOA survived the operative procedure, and 6 survived to 30 days. By contrast, 8 patients were treated with RT, and none survived to 30 days. Ten of the 16 patients who underwent REBOA experienced an improvement in hemodynamic status, with systolic blood pressure improving to a mean of 131.83 mm Hg (±8.24) and improvement of heart rate to 87.5 (±5.47). One survivor developed a common femoral pseudoaneurysm.
Compared with nonsurvivors, REBOA patients who survived had a significant increase in Initial Glasgow Coma scores (15.0 vs. 6.18; P less than .05), and higher initial platelet counts (276.40 vs. 124.75; P = .01). Survivors also had higher initial postoperative systolic blood pressure (151.40 mm Hg vs. 112.33; P = .05), and a higher mean postoperative arterial blood pressure (109.00 mm Hg vs. 72.78; P = .01).
Overall, the findings were similar to those reported in previous multicenter trials.
The researchers pointed out that REBOA does not replace RT. The latter procedure is still appropriate for some moribund patients with super-diaphragmatic injury and in patients who require open cardiac massage.
The techniques are not mutually exclusive – two patients in the sample were treated with both techniques.
The researchers also mentioned some future possibilities for REBOA. Research in animals has demonstrated the promise of partial REBOA, in which an automated system can partially inflate the balloon and gradually deflate it as the patient’s vital signs improve. That can lighten the load for surgeons and anesthesiologists, according to Dr. Smith. “We look forward to developing that technology in the future,” he said.
The funding source was not disclosed. Dr. Smith is on the speakers bureau for Prytime Medical and is a consultant for Boehringer Laboratory LLC.
SCOTTSDALE, ARIZ. – In a small, single-center study of patients with subdiaphragmatic hemorrhage, resuscitative endovascular balloon occlusion of the aorta (REBOA) improved hemodynamic status and 30-day survival rates, compared with resuscitative thoracotomy (RT).
Although the technique was first developed during the Korean War, REBOA never really caught on, possibly because of limitations in endovascular technology. But recent advances in surgical technique have revitalized interest.
Despite the success of the study, some audience members expressed concerns about the skill set required. One questioner pointed out that emergency department physicians may be tempted to use the technique, even though they may not possess the requisite catheter and wire skills. That is a legitimate concern, according to senior author R. Stephen Smith, MD, FACS, professor of acute care surgery at the University of Florida, Gainesville. But this is already happening, he said. “They’ve already done it in the field in Britain, and most are placed by nonsurgeons in Japan. Frankly, we need to pay particular attention to the skills of those emergency medicine physicians, because the average emergency medicine physician at this point really doesn’t have the catheter or wire-based skills to do this safely,” Dr. Smith said at the annual meeting of the Western Surgical Association.
The researchers examined outcomes in patients who underwent REBOA versus RT over a 21-month (2015-2017) period at their institution. Before adopting REBOA, attending surgeons and senior surgical residents attended a 1.5-hour slide presentation combined with simulation training. No external course was required. Operating room personnel received a 30-minute slide presentation. The procedures were conducted in a dedicated trauma operating room equipped with imaging.
Sixteen patients underwent REBOA during the study period, with a mean injury severity score of 38.6. Preoperative hemoglobin levels ranged from 5 to 14.4 mg/dL, and the majority were acidotic because of trauma.
Fourteen of the 16 patients who underwent REBOA survived the operative procedure, and 6 survived to 30 days. By contrast, 8 patients were treated with RT, and none survived to 30 days. Ten of the 16 patients who underwent REBOA experienced an improvement in hemodynamic status, with systolic blood pressure improving to a mean of 131.83 mm Hg (±8.24) and improvement of heart rate to 87.5 (±5.47). One survivor developed a common femoral pseudoaneurysm.
Compared with nonsurvivors, REBOA patients who survived had a significant increase in Initial Glasgow Coma scores (15.0 vs. 6.18; P less than .05), and higher initial platelet counts (276.40 vs. 124.75; P = .01). Survivors also had higher initial postoperative systolic blood pressure (151.40 mm Hg vs. 112.33; P = .05), and a higher mean postoperative arterial blood pressure (109.00 mm Hg vs. 72.78; P = .01).
Overall, the findings were similar to those reported in previous multicenter trials.
The researchers pointed out that REBOA does not replace RT. The latter procedure is still appropriate for some moribund patients with super-diaphragmatic injury and in patients who require open cardiac massage.
The techniques are not mutually exclusive – two patients in the sample were treated with both techniques.
The researchers also mentioned some future possibilities for REBOA. Research in animals has demonstrated the promise of partial REBOA, in which an automated system can partially inflate the balloon and gradually deflate it as the patient’s vital signs improve. That can lighten the load for surgeons and anesthesiologists, according to Dr. Smith. “We look forward to developing that technology in the future,” he said.
The funding source was not disclosed. Dr. Smith is on the speakers bureau for Prytime Medical and is a consultant for Boehringer Laboratory LLC.
SCOTTSDALE, ARIZ. – In a small, single-center study of patients with subdiaphragmatic hemorrhage, resuscitative endovascular balloon occlusion of the aorta (REBOA) improved hemodynamic status and 30-day survival rates, compared with resuscitative thoracotomy (RT).
Although the technique was first developed during the Korean War, REBOA never really caught on, possibly because of limitations in endovascular technology. But recent advances in surgical technique have revitalized interest.
Despite the success of the study, some audience members expressed concerns about the skill set required. One questioner pointed out that emergency department physicians may be tempted to use the technique, even though they may not possess the requisite catheter and wire skills. That is a legitimate concern, according to senior author R. Stephen Smith, MD, FACS, professor of acute care surgery at the University of Florida, Gainesville. But this is already happening, he said. “They’ve already done it in the field in Britain, and most are placed by nonsurgeons in Japan. Frankly, we need to pay particular attention to the skills of those emergency medicine physicians, because the average emergency medicine physician at this point really doesn’t have the catheter or wire-based skills to do this safely,” Dr. Smith said at the annual meeting of the Western Surgical Association.
The researchers examined outcomes in patients who underwent REBOA versus RT over a 21-month (2015-2017) period at their institution. Before adopting REBOA, attending surgeons and senior surgical residents attended a 1.5-hour slide presentation combined with simulation training. No external course was required. Operating room personnel received a 30-minute slide presentation. The procedures were conducted in a dedicated trauma operating room equipped with imaging.
Sixteen patients underwent REBOA during the study period, with a mean injury severity score of 38.6. Preoperative hemoglobin levels ranged from 5 to 14.4 mg/dL, and the majority were acidotic because of trauma.
Fourteen of the 16 patients who underwent REBOA survived the operative procedure, and 6 survived to 30 days. By contrast, 8 patients were treated with RT, and none survived to 30 days. Ten of the 16 patients who underwent REBOA experienced an improvement in hemodynamic status, with systolic blood pressure improving to a mean of 131.83 mm Hg (±8.24) and improvement of heart rate to 87.5 (±5.47). One survivor developed a common femoral pseudoaneurysm.
Compared with nonsurvivors, REBOA patients who survived had a significant increase in Initial Glasgow Coma scores (15.0 vs. 6.18; P less than .05), and higher initial platelet counts (276.40 vs. 124.75; P = .01). Survivors also had higher initial postoperative systolic blood pressure (151.40 mm Hg vs. 112.33; P = .05), and a higher mean postoperative arterial blood pressure (109.00 mm Hg vs. 72.78; P = .01).
Overall, the findings were similar to those reported in previous multicenter trials.
The researchers pointed out that REBOA does not replace RT. The latter procedure is still appropriate for some moribund patients with super-diaphragmatic injury and in patients who require open cardiac massage.
The techniques are not mutually exclusive – two patients in the sample were treated with both techniques.
The researchers also mentioned some future possibilities for REBOA. Research in animals has demonstrated the promise of partial REBOA, in which an automated system can partially inflate the balloon and gradually deflate it as the patient’s vital signs improve. That can lighten the load for surgeons and anesthesiologists, according to Dr. Smith. “We look forward to developing that technology in the future,” he said.
The funding source was not disclosed. Dr. Smith is on the speakers bureau for Prytime Medical and is a consultant for Boehringer Laboratory LLC.
AT WSA 2017
Key clinical point: REBOA improved hematological outcomes and survival rates, compared with resuscitative thoracotomy.
Major finding: Six of 16 patients in the REBOA group survived to 30 days, compared with none of the 8 resuscitative thoracotomy patients.
Data source: Retrospective analysis of 24 patients at a single center.
Disclosures: The funding source was not disclosed. Dr. Smith is on the speakers bureau for Prytime Medical and is a consultant for Boehringer Laboratory LLC.
A compounded, nonbenzodiazepine option for treating acute anxiety
Treating short-term or situational anxiety or anxiety attacks with benzodiazepines carries the risk of withdrawal and dependence. Other options include various antidepressants and buspirone. Although such medications decrease overall anxiety and can prevent anxiety from building, they are not effective for breakthrough anxiety. Other mainstays are antihistamines, antipsychotics, or newer antiepileptics such as gabapentin and pregabalin, but none of these have strong clinical literature support regarding their effectiveness for treating anxiety disorders.
PanX compounded medications are dual drug combinations of a beta blocker plus an antiemetic antimuscarinic agent.1 They are designed and patented for as-needed treatment of anxiety disorders without using any controlled substances. Compounded medications are not FDA-approved, but are commercially available and subject to Section 503A of the Federal Food, Drug, and Cosmetics Act of 2013.2
In PanX medications, the beta blocker is intended to address the sympathetic cardiovascular symptoms of anxiety. Beta adrenergic receptor antagonists have been prescribed off-label for decades to treat social anxiety disorder, including performance anxiety. At least 7 beta blockers—atenolol, propranolol, pindolol, timolol, nadolol, betaxolol, and oxprenolol—have been reported to have anxiolytic effects, although these are limited to cardiovascular symptoms of anxiety.1
However, there is a need to augment the limited effects of the beta blocker with another agent, such as an antimuscarinic agent, which is intended for parasympathetic noncardiovascular and CNS symptoms of anxiety. Scopolamine is a preferred antimuscarinic because it has been known for over a century to exhibit anxiolytic effects.3 Scopolamine’s mechanism of action is antagonism of acetylcholine binding to the M1 and/or M2 muscarinic receptors.4
We present a case of a patient who needed a nonbenzodiazepine treatment for acute anxiety. She received a compounded PanX combination of the beta-1 selective beta blocker atenolol, 25 mg, plus scopolamine hydrobromide, 0.2 mg, as needed for acute anxiety.
Case report
Acute anxiety, benzodiazepine abuse
Ms. L, age 30, with a family history of depression and anxiety, has had anxiety, depression, and posttraumatic stress disorder since she was in her mid-20s. She is evaluated in a 30-day rehabilitation program for alprazolam abuse. She is detoxed from alprazolam and stabilized with lurasidone, 60 mg once in the morning, gabapentin, 1,200 mg 4 times a day, and quetiapine, 125 mg as needed for sleep.
Ms. L improves significantly and is transferred to an intensive outpatient program. While there, she experiences increased periods of anxiety related to ruminative thoughts about relationship, occupational, and living stressors. She requests a medication for breakthrough anxiety and recognizes that, because of her history, a benzodiazepine is not medically indicated.
Ms. L signs a consent to a physician-sponsored trial of a PanX medication consisting of orally disintegrating tablets of atenolol, 25 mg, plus scopolamine hydrobromide, 0.2 mg, (in a polyglycol troche base plus mannitol, silica gel, and Steviol glycosides), which is prepared by a compounding pharmacy. Over 6 days, she takes the PanX combination 3 times. Immediately before she takes the medication, her symptoms are intense anxiety, nervousness, and agitation; feelings of panic; increased heart rate and palpitations; and shortness of breath. Ms. L says these symptoms developed approximately 20 minutes before she took the PanX combination. Approximately 30 minutes after taking the medication, she describes having a complete resolution of these symptoms that lasted for 4 hours. She says the medication “calmed [her] down” and had a “Klonopin or benzo-like effect.” She notes that her heart rate slowed quickly, followed by her breathing, and that she also was “more focused.” No information regarding her heart rate or blood pressure when she experienced the symptoms or after treatment is available. She denies experiencing dry mouth, dizziness, fatigue, sleepiness, blurred vision, or confusion.
Targets for future research
This case provides some preliminary clinical evidence of a rapid anxiolytic effect from a novel medication—a beta blocker plus scopolamine combination—that was beneficial in a situation where it may be likely that a benzodiazepine would have been utilized. This is our first case report documenting a trial of any PanX combination (ie, a combination of any beta blocker with any antimuscarinic agent) regarding anxiolytic efficacy and timing, tolerability, and adverse effects. With recognition that this is a report of 1 patient who took the medication 3 times, there is much that is not known.
Additional clinical studies are needed to evaluate the efficacy, tolerability, and adverse effects associated with using a beta blocker/antiemetic antimuscarinic combination to treat acute anxiety. Medication interactions also need to be considered. Whether this combination medication would be best for treating breakthrough anxiety or other acute anxiety episodes, and/or used as a regularly dosed medication is unknown. With documented risks of long-term benzodiazepine use, other novel therapeutics, such as the atenolol/scopolamine combination, may be welcome in treating acute anxiety.
1. Dooley TP. Treating anxiety with either beta blockers or antiemetic antimuscarinic drugs: a review. Mental Health Fam Med. 2015;11(1):89-99.
2. U.S. Food and Drug Administration. Guidance, compliance and regulatory information: compounding. Section 503A of the Federal Food, Drug, and Cosmetic Act. https://www.fda.gov/drugs/guidancecomplianceregulatoryinformation/pharmacycompounding/ucm376733.htm. Updated December 12, 2013. Accessed October 25, 2017.
3. Houde A. Scopolamine: a physiological and clinical study. The Am J Clin Med. 1906;13:365-367.
4. Witkin JM, Overshiner C, Li X, et al. M1 and m2 muscarinic receptor subtypes regulate antidepressant-like effects of the rapidly acting antidepressant scopolamine. J Pharmacol Exp Ther. 2014;351(2):448-456.
Treating short-term or situational anxiety or anxiety attacks with benzodiazepines carries the risk of withdrawal and dependence. Other options include various antidepressants and buspirone. Although such medications decrease overall anxiety and can prevent anxiety from building, they are not effective for breakthrough anxiety. Other mainstays are antihistamines, antipsychotics, or newer antiepileptics such as gabapentin and pregabalin, but none of these have strong clinical literature support regarding their effectiveness for treating anxiety disorders.
PanX compounded medications are dual drug combinations of a beta blocker plus an antiemetic antimuscarinic agent.1 They are designed and patented for as-needed treatment of anxiety disorders without using any controlled substances. Compounded medications are not FDA-approved, but are commercially available and subject to Section 503A of the Federal Food, Drug, and Cosmetics Act of 2013.2
In PanX medications, the beta blocker is intended to address the sympathetic cardiovascular symptoms of anxiety. Beta adrenergic receptor antagonists have been prescribed off-label for decades to treat social anxiety disorder, including performance anxiety. At least 7 beta blockers—atenolol, propranolol, pindolol, timolol, nadolol, betaxolol, and oxprenolol—have been reported to have anxiolytic effects, although these are limited to cardiovascular symptoms of anxiety.1
However, there is a need to augment the limited effects of the beta blocker with another agent, such as an antimuscarinic agent, which is intended for parasympathetic noncardiovascular and CNS symptoms of anxiety. Scopolamine is a preferred antimuscarinic because it has been known for over a century to exhibit anxiolytic effects.3 Scopolamine’s mechanism of action is antagonism of acetylcholine binding to the M1 and/or M2 muscarinic receptors.4
We present a case of a patient who needed a nonbenzodiazepine treatment for acute anxiety. She received a compounded PanX combination of the beta-1 selective beta blocker atenolol, 25 mg, plus scopolamine hydrobromide, 0.2 mg, as needed for acute anxiety.
Case report
Acute anxiety, benzodiazepine abuse
Ms. L, age 30, with a family history of depression and anxiety, has had anxiety, depression, and posttraumatic stress disorder since she was in her mid-20s. She is evaluated in a 30-day rehabilitation program for alprazolam abuse. She is detoxed from alprazolam and stabilized with lurasidone, 60 mg once in the morning, gabapentin, 1,200 mg 4 times a day, and quetiapine, 125 mg as needed for sleep.
Ms. L improves significantly and is transferred to an intensive outpatient program. While there, she experiences increased periods of anxiety related to ruminative thoughts about relationship, occupational, and living stressors. She requests a medication for breakthrough anxiety and recognizes that, because of her history, a benzodiazepine is not medically indicated.
Ms. L signs a consent to a physician-sponsored trial of a PanX medication consisting of orally disintegrating tablets of atenolol, 25 mg, plus scopolamine hydrobromide, 0.2 mg, (in a polyglycol troche base plus mannitol, silica gel, and Steviol glycosides), which is prepared by a compounding pharmacy. Over 6 days, she takes the PanX combination 3 times. Immediately before she takes the medication, her symptoms are intense anxiety, nervousness, and agitation; feelings of panic; increased heart rate and palpitations; and shortness of breath. Ms. L says these symptoms developed approximately 20 minutes before she took the PanX combination. Approximately 30 minutes after taking the medication, she describes having a complete resolution of these symptoms that lasted for 4 hours. She says the medication “calmed [her] down” and had a “Klonopin or benzo-like effect.” She notes that her heart rate slowed quickly, followed by her breathing, and that she also was “more focused.” No information regarding her heart rate or blood pressure when she experienced the symptoms or after treatment is available. She denies experiencing dry mouth, dizziness, fatigue, sleepiness, blurred vision, or confusion.
Targets for future research
This case provides some preliminary clinical evidence of a rapid anxiolytic effect from a novel medication—a beta blocker plus scopolamine combination—that was beneficial in a situation where it may be likely that a benzodiazepine would have been utilized. This is our first case report documenting a trial of any PanX combination (ie, a combination of any beta blocker with any antimuscarinic agent) regarding anxiolytic efficacy and timing, tolerability, and adverse effects. With recognition that this is a report of 1 patient who took the medication 3 times, there is much that is not known.
Additional clinical studies are needed to evaluate the efficacy, tolerability, and adverse effects associated with using a beta blocker/antiemetic antimuscarinic combination to treat acute anxiety. Medication interactions also need to be considered. Whether this combination medication would be best for treating breakthrough anxiety or other acute anxiety episodes, and/or used as a regularly dosed medication is unknown. With documented risks of long-term benzodiazepine use, other novel therapeutics, such as the atenolol/scopolamine combination, may be welcome in treating acute anxiety.
Treating short-term or situational anxiety or anxiety attacks with benzodiazepines carries the risk of withdrawal and dependence. Other options include various antidepressants and buspirone. Although such medications decrease overall anxiety and can prevent anxiety from building, they are not effective for breakthrough anxiety. Other mainstays are antihistamines, antipsychotics, or newer antiepileptics such as gabapentin and pregabalin, but none of these have strong clinical literature support regarding their effectiveness for treating anxiety disorders.
PanX compounded medications are dual drug combinations of a beta blocker plus an antiemetic antimuscarinic agent.1 They are designed and patented for as-needed treatment of anxiety disorders without using any controlled substances. Compounded medications are not FDA-approved, but are commercially available and subject to Section 503A of the Federal Food, Drug, and Cosmetics Act of 2013.2
In PanX medications, the beta blocker is intended to address the sympathetic cardiovascular symptoms of anxiety. Beta adrenergic receptor antagonists have been prescribed off-label for decades to treat social anxiety disorder, including performance anxiety. At least 7 beta blockers—atenolol, propranolol, pindolol, timolol, nadolol, betaxolol, and oxprenolol—have been reported to have anxiolytic effects, although these are limited to cardiovascular symptoms of anxiety.1
However, there is a need to augment the limited effects of the beta blocker with another agent, such as an antimuscarinic agent, which is intended for parasympathetic noncardiovascular and CNS symptoms of anxiety. Scopolamine is a preferred antimuscarinic because it has been known for over a century to exhibit anxiolytic effects.3 Scopolamine’s mechanism of action is antagonism of acetylcholine binding to the M1 and/or M2 muscarinic receptors.4
We present a case of a patient who needed a nonbenzodiazepine treatment for acute anxiety. She received a compounded PanX combination of the beta-1 selective beta blocker atenolol, 25 mg, plus scopolamine hydrobromide, 0.2 mg, as needed for acute anxiety.
Case report
Acute anxiety, benzodiazepine abuse
Ms. L, age 30, with a family history of depression and anxiety, has had anxiety, depression, and posttraumatic stress disorder since she was in her mid-20s. She is evaluated in a 30-day rehabilitation program for alprazolam abuse. She is detoxed from alprazolam and stabilized with lurasidone, 60 mg once in the morning, gabapentin, 1,200 mg 4 times a day, and quetiapine, 125 mg as needed for sleep.
Ms. L improves significantly and is transferred to an intensive outpatient program. While there, she experiences increased periods of anxiety related to ruminative thoughts about relationship, occupational, and living stressors. She requests a medication for breakthrough anxiety and recognizes that, because of her history, a benzodiazepine is not medically indicated.
Ms. L signs a consent to a physician-sponsored trial of a PanX medication consisting of orally disintegrating tablets of atenolol, 25 mg, plus scopolamine hydrobromide, 0.2 mg, (in a polyglycol troche base plus mannitol, silica gel, and Steviol glycosides), which is prepared by a compounding pharmacy. Over 6 days, she takes the PanX combination 3 times. Immediately before she takes the medication, her symptoms are intense anxiety, nervousness, and agitation; feelings of panic; increased heart rate and palpitations; and shortness of breath. Ms. L says these symptoms developed approximately 20 minutes before she took the PanX combination. Approximately 30 minutes after taking the medication, she describes having a complete resolution of these symptoms that lasted for 4 hours. She says the medication “calmed [her] down” and had a “Klonopin or benzo-like effect.” She notes that her heart rate slowed quickly, followed by her breathing, and that she also was “more focused.” No information regarding her heart rate or blood pressure when she experienced the symptoms or after treatment is available. She denies experiencing dry mouth, dizziness, fatigue, sleepiness, blurred vision, or confusion.
Targets for future research
This case provides some preliminary clinical evidence of a rapid anxiolytic effect from a novel medication—a beta blocker plus scopolamine combination—that was beneficial in a situation where it may be likely that a benzodiazepine would have been utilized. This is our first case report documenting a trial of any PanX combination (ie, a combination of any beta blocker with any antimuscarinic agent) regarding anxiolytic efficacy and timing, tolerability, and adverse effects. With recognition that this is a report of 1 patient who took the medication 3 times, there is much that is not known.
Additional clinical studies are needed to evaluate the efficacy, tolerability, and adverse effects associated with using a beta blocker/antiemetic antimuscarinic combination to treat acute anxiety. Medication interactions also need to be considered. Whether this combination medication would be best for treating breakthrough anxiety or other acute anxiety episodes, and/or used as a regularly dosed medication is unknown. With documented risks of long-term benzodiazepine use, other novel therapeutics, such as the atenolol/scopolamine combination, may be welcome in treating acute anxiety.
1. Dooley TP. Treating anxiety with either beta blockers or antiemetic antimuscarinic drugs: a review. Mental Health Fam Med. 2015;11(1):89-99.
2. U.S. Food and Drug Administration. Guidance, compliance and regulatory information: compounding. Section 503A of the Federal Food, Drug, and Cosmetic Act. https://www.fda.gov/drugs/guidancecomplianceregulatoryinformation/pharmacycompounding/ucm376733.htm. Updated December 12, 2013. Accessed October 25, 2017.
3. Houde A. Scopolamine: a physiological and clinical study. The Am J Clin Med. 1906;13:365-367.
4. Witkin JM, Overshiner C, Li X, et al. M1 and m2 muscarinic receptor subtypes regulate antidepressant-like effects of the rapidly acting antidepressant scopolamine. J Pharmacol Exp Ther. 2014;351(2):448-456.
1. Dooley TP. Treating anxiety with either beta blockers or antiemetic antimuscarinic drugs: a review. Mental Health Fam Med. 2015;11(1):89-99.
2. U.S. Food and Drug Administration. Guidance, compliance and regulatory information: compounding. Section 503A of the Federal Food, Drug, and Cosmetic Act. https://www.fda.gov/drugs/guidancecomplianceregulatoryinformation/pharmacycompounding/ucm376733.htm. Updated December 12, 2013. Accessed October 25, 2017.
3. Houde A. Scopolamine: a physiological and clinical study. The Am J Clin Med. 1906;13:365-367.
4. Witkin JM, Overshiner C, Li X, et al. M1 and m2 muscarinic receptor subtypes regulate antidepressant-like effects of the rapidly acting antidepressant scopolamine. J Pharmacol Exp Ther. 2014;351(2):448-456.
