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Distinguish ‘sleepiness’ from ‘fatigue’ to help diagnose hypersomnia
, according to Ruth M. Benca, MD, PhD.
Fatigue, feeling tired, and lack of energy are common complaints that accompany insomnia and psychiatric disorders, but these patients do not fall asleep quickly in a restful setting and will have normal multiple sleep latency test (MSLT) in a laboratory. In contrast, excessive sleepiness, or hypersomnia, occurs when patients sleep more than 11 hours in a 24-hour period.
Patients with hypersomnia fall asleep in low stimulus situations and devote more energy to staying awake during situations. This excessive sleepiness can be dangerous in the context of activities such as driving, Dr. Benca said. These patients will also have low sleep latencies (< 8 minutes) when tested through MSLT in a laboratory, she added. Patients with hypersomnia may be irritable, have reduced attention or concentration, and have poor memory.
The primary cause of hypersomnia is sleep deprivation, but “both hypersomnia and fatigue are common complaints in psychiatric patients, including depression, bipolar disorder, seasonal affective disorder, [and] psychosis,” Dr. Benca explained. Other causes of hypersomnia include sleep disorders such as sleep apnea, circadian rhythm disorders and periodic limb movements, neurologic or degenerative disorders, mental disorders, and effects of medication. Idiopathic hypersomnia and narcolepsy are uncommon causes of hypersomnia and usually diagnosed in a sleep laboratory setting, she said.
In patients with depression, hypersomnia looks like patients having “nonimperative sleepiness,” Dr. Benca said. “They may spend a lot of time in bed; they may report long and nonrefreshing naps or long sleep time.”
There also is an issue with sleep inertia in patients with depression and hypersomnia, and with patients taking a long time to wake up and begin their day. In these patients, “when we put them in the sleep laboratory, the objective studies generally do not show that they are excessively sleepy, despite their reports of subjectively being sleepy,” she said.
There is not much objective MSLT or subjective measure data for hypersomnia in patients with schizophrenia despite these patients reporting daytime sleepiness or hypersomnolence, Dr. Benca admitted. Hypersomnia in patients with schizophrenia may be related to drug effects, poor sleep hygiene, circadian rhythm abnormalities, or comorbid sleep disorders. “Excessive sleepiness may also be related to the schizophrenia itself,” she said.
Treatments for hypersomnia
The first priority for patients with hypersomnia is to avoid sleep deprivation and practice good sleep hygiene – factors that are important both in insomnia and hypersomnia. “Make sure that patients are having adequate time in bed and having regular hours of sleep,” Dr. Benca said.
For patients with comorbid psychiatric, medical and sleep disorders, focus on getting rid of medications that may cause sleepiness, including sedating medications and antidepressants, and consider using stimulants if appropriate. While there are Food and Drug Administration–approved medications for narcolepsy and some are approved for hypersomnia in patients with obstructive sleep apnea (OSA), none are officially approved to treat hypersomnia in psychiatric patients.
“Whenever we use these drugs for those reasons, we’re using them off label,” Dr. Benca said.
Modafinil/armodafinil, approved for narcolepsy, shift-work disorder, and OSA in Ehlers-Danlos syndrome, is one off-label option for patients with hypersomnia. “They are lower potency and less addictive than the amphetamines, [with] fewer side effects,” Dr. Benca explained, but should be prescribed with caution in some women because of potential reduced efficacy of oral contraceptives. Side effects of modafinil include headache, nausea, eosinophilia, diarrhea, dry mouth, and anorexia.
Methylphenidate is another option for hypersomnia, available in racemic mixture, pure D-isomer, and time-release formulations.
Patients taking methylphenidate may experience nervousness, insomnia, anorexia, nausea, dizziness, hypertension, hypotension, hypersensitivity reactions, tachycardia, and headache as side effects.
For patients with central nervous system hypersomnias, amphetamines can be used, with methamphetamines having a “very similar profile” and similar side effects, including insomnia, restlessness, tachycardia, dizziness, diarrhea, constipation, hypertension, impotence, and rare cases of psychotic episodes.
Practice parameters released by the American Academy of Sleep Medicine in 2007 suggest that modafinil may have efficacy in idiopathic hypersomnia, Parkinson’s disease, myotonic dystrophy, and multiple sclerosis. The practice parameters also suggest hypersomnias of central origin can be treated with modafinil, amphetamine, methamphetamine, dextroamphetamine, and methylphenidate based on evidence or “long history of use” (Sleep. 2007;30:1705-11).
“Interestingly, there is no mention of psychiatric disorders in these practice parameters, and they report that there are mixed results using stimulants off label for sleepiness and fatigue in traumatic brain injury and poststroke fatigue,” Dr. Benca said.
Dr. Benca reported that she is a consultant to Eisai, Idorsia, Jazz, Merck, and Sunovion. Global Academy and this news organization are owned by the same parent company.
, according to Ruth M. Benca, MD, PhD.
Fatigue, feeling tired, and lack of energy are common complaints that accompany insomnia and psychiatric disorders, but these patients do not fall asleep quickly in a restful setting and will have normal multiple sleep latency test (MSLT) in a laboratory. In contrast, excessive sleepiness, or hypersomnia, occurs when patients sleep more than 11 hours in a 24-hour period.
Patients with hypersomnia fall asleep in low stimulus situations and devote more energy to staying awake during situations. This excessive sleepiness can be dangerous in the context of activities such as driving, Dr. Benca said. These patients will also have low sleep latencies (< 8 minutes) when tested through MSLT in a laboratory, she added. Patients with hypersomnia may be irritable, have reduced attention or concentration, and have poor memory.
The primary cause of hypersomnia is sleep deprivation, but “both hypersomnia and fatigue are common complaints in psychiatric patients, including depression, bipolar disorder, seasonal affective disorder, [and] psychosis,” Dr. Benca explained. Other causes of hypersomnia include sleep disorders such as sleep apnea, circadian rhythm disorders and periodic limb movements, neurologic or degenerative disorders, mental disorders, and effects of medication. Idiopathic hypersomnia and narcolepsy are uncommon causes of hypersomnia and usually diagnosed in a sleep laboratory setting, she said.
In patients with depression, hypersomnia looks like patients having “nonimperative sleepiness,” Dr. Benca said. “They may spend a lot of time in bed; they may report long and nonrefreshing naps or long sleep time.”
There also is an issue with sleep inertia in patients with depression and hypersomnia, and with patients taking a long time to wake up and begin their day. In these patients, “when we put them in the sleep laboratory, the objective studies generally do not show that they are excessively sleepy, despite their reports of subjectively being sleepy,” she said.
There is not much objective MSLT or subjective measure data for hypersomnia in patients with schizophrenia despite these patients reporting daytime sleepiness or hypersomnolence, Dr. Benca admitted. Hypersomnia in patients with schizophrenia may be related to drug effects, poor sleep hygiene, circadian rhythm abnormalities, or comorbid sleep disorders. “Excessive sleepiness may also be related to the schizophrenia itself,” she said.
Treatments for hypersomnia
The first priority for patients with hypersomnia is to avoid sleep deprivation and practice good sleep hygiene – factors that are important both in insomnia and hypersomnia. “Make sure that patients are having adequate time in bed and having regular hours of sleep,” Dr. Benca said.
For patients with comorbid psychiatric, medical and sleep disorders, focus on getting rid of medications that may cause sleepiness, including sedating medications and antidepressants, and consider using stimulants if appropriate. While there are Food and Drug Administration–approved medications for narcolepsy and some are approved for hypersomnia in patients with obstructive sleep apnea (OSA), none are officially approved to treat hypersomnia in psychiatric patients.
“Whenever we use these drugs for those reasons, we’re using them off label,” Dr. Benca said.
Modafinil/armodafinil, approved for narcolepsy, shift-work disorder, and OSA in Ehlers-Danlos syndrome, is one off-label option for patients with hypersomnia. “They are lower potency and less addictive than the amphetamines, [with] fewer side effects,” Dr. Benca explained, but should be prescribed with caution in some women because of potential reduced efficacy of oral contraceptives. Side effects of modafinil include headache, nausea, eosinophilia, diarrhea, dry mouth, and anorexia.
Methylphenidate is another option for hypersomnia, available in racemic mixture, pure D-isomer, and time-release formulations.
Patients taking methylphenidate may experience nervousness, insomnia, anorexia, nausea, dizziness, hypertension, hypotension, hypersensitivity reactions, tachycardia, and headache as side effects.
For patients with central nervous system hypersomnias, amphetamines can be used, with methamphetamines having a “very similar profile” and similar side effects, including insomnia, restlessness, tachycardia, dizziness, diarrhea, constipation, hypertension, impotence, and rare cases of psychotic episodes.
Practice parameters released by the American Academy of Sleep Medicine in 2007 suggest that modafinil may have efficacy in idiopathic hypersomnia, Parkinson’s disease, myotonic dystrophy, and multiple sclerosis. The practice parameters also suggest hypersomnias of central origin can be treated with modafinil, amphetamine, methamphetamine, dextroamphetamine, and methylphenidate based on evidence or “long history of use” (Sleep. 2007;30:1705-11).
“Interestingly, there is no mention of psychiatric disorders in these practice parameters, and they report that there are mixed results using stimulants off label for sleepiness and fatigue in traumatic brain injury and poststroke fatigue,” Dr. Benca said.
Dr. Benca reported that she is a consultant to Eisai, Idorsia, Jazz, Merck, and Sunovion. Global Academy and this news organization are owned by the same parent company.
, according to Ruth M. Benca, MD, PhD.
Fatigue, feeling tired, and lack of energy are common complaints that accompany insomnia and psychiatric disorders, but these patients do not fall asleep quickly in a restful setting and will have normal multiple sleep latency test (MSLT) in a laboratory. In contrast, excessive sleepiness, or hypersomnia, occurs when patients sleep more than 11 hours in a 24-hour period.
Patients with hypersomnia fall asleep in low stimulus situations and devote more energy to staying awake during situations. This excessive sleepiness can be dangerous in the context of activities such as driving, Dr. Benca said. These patients will also have low sleep latencies (< 8 minutes) when tested through MSLT in a laboratory, she added. Patients with hypersomnia may be irritable, have reduced attention or concentration, and have poor memory.
The primary cause of hypersomnia is sleep deprivation, but “both hypersomnia and fatigue are common complaints in psychiatric patients, including depression, bipolar disorder, seasonal affective disorder, [and] psychosis,” Dr. Benca explained. Other causes of hypersomnia include sleep disorders such as sleep apnea, circadian rhythm disorders and periodic limb movements, neurologic or degenerative disorders, mental disorders, and effects of medication. Idiopathic hypersomnia and narcolepsy are uncommon causes of hypersomnia and usually diagnosed in a sleep laboratory setting, she said.
In patients with depression, hypersomnia looks like patients having “nonimperative sleepiness,” Dr. Benca said. “They may spend a lot of time in bed; they may report long and nonrefreshing naps or long sleep time.”
There also is an issue with sleep inertia in patients with depression and hypersomnia, and with patients taking a long time to wake up and begin their day. In these patients, “when we put them in the sleep laboratory, the objective studies generally do not show that they are excessively sleepy, despite their reports of subjectively being sleepy,” she said.
There is not much objective MSLT or subjective measure data for hypersomnia in patients with schizophrenia despite these patients reporting daytime sleepiness or hypersomnolence, Dr. Benca admitted. Hypersomnia in patients with schizophrenia may be related to drug effects, poor sleep hygiene, circadian rhythm abnormalities, or comorbid sleep disorders. “Excessive sleepiness may also be related to the schizophrenia itself,” she said.
Treatments for hypersomnia
The first priority for patients with hypersomnia is to avoid sleep deprivation and practice good sleep hygiene – factors that are important both in insomnia and hypersomnia. “Make sure that patients are having adequate time in bed and having regular hours of sleep,” Dr. Benca said.
For patients with comorbid psychiatric, medical and sleep disorders, focus on getting rid of medications that may cause sleepiness, including sedating medications and antidepressants, and consider using stimulants if appropriate. While there are Food and Drug Administration–approved medications for narcolepsy and some are approved for hypersomnia in patients with obstructive sleep apnea (OSA), none are officially approved to treat hypersomnia in psychiatric patients.
“Whenever we use these drugs for those reasons, we’re using them off label,” Dr. Benca said.
Modafinil/armodafinil, approved for narcolepsy, shift-work disorder, and OSA in Ehlers-Danlos syndrome, is one off-label option for patients with hypersomnia. “They are lower potency and less addictive than the amphetamines, [with] fewer side effects,” Dr. Benca explained, but should be prescribed with caution in some women because of potential reduced efficacy of oral contraceptives. Side effects of modafinil include headache, nausea, eosinophilia, diarrhea, dry mouth, and anorexia.
Methylphenidate is another option for hypersomnia, available in racemic mixture, pure D-isomer, and time-release formulations.
Patients taking methylphenidate may experience nervousness, insomnia, anorexia, nausea, dizziness, hypertension, hypotension, hypersensitivity reactions, tachycardia, and headache as side effects.
For patients with central nervous system hypersomnias, amphetamines can be used, with methamphetamines having a “very similar profile” and similar side effects, including insomnia, restlessness, tachycardia, dizziness, diarrhea, constipation, hypertension, impotence, and rare cases of psychotic episodes.
Practice parameters released by the American Academy of Sleep Medicine in 2007 suggest that modafinil may have efficacy in idiopathic hypersomnia, Parkinson’s disease, myotonic dystrophy, and multiple sclerosis. The practice parameters also suggest hypersomnias of central origin can be treated with modafinil, amphetamine, methamphetamine, dextroamphetamine, and methylphenidate based on evidence or “long history of use” (Sleep. 2007;30:1705-11).
“Interestingly, there is no mention of psychiatric disorders in these practice parameters, and they report that there are mixed results using stimulants off label for sleepiness and fatigue in traumatic brain injury and poststroke fatigue,” Dr. Benca said.
Dr. Benca reported that she is a consultant to Eisai, Idorsia, Jazz, Merck, and Sunovion. Global Academy and this news organization are owned by the same parent company.
FROM PSYCHOPHARMACOLOGY UPDATE
Choosing pharmacotherapy for bipolar disorder requires a risk-benefit analysis
When selecting pharmacotherapy for patients with bipolar disorder, clinical and prognostic correlates will ultimately influence what treatments make the most sense for a patient – but the process is a balancing act, according to Joseph F. Goldberg, MD.
“Everything we do in medicine in general, and psychiatry, and bipolar disorder in particular is a risk-benefit analysis,” Dr. Goldberg said at the virtual Psychopharmacology Update presented by Current Psychiatry and Global Academy for Medical Education. “Everything has its side effects. We’re always balancing risks and benefits.”
Patients with bipolar disorder often present with three common subtypes of the illness: Those who have associated psychosis, comorbid anxiety disorders, and comorbid ADHD. “These are three common presentations of the many, many kinds of presentations,” said Dr. Goldberg, clinical professor of psychiatry at the Icahn School of Medicine at Mount Sinai in New York.
Bipolar disorder with associated psychosis
In the case of bipolar I disorder, more than 50% of manic episodes have some element of psychosis, with as many as 10% of patients showing signs of delusions 2 years after an episode, Dr. Goldberg explained. In these patients, mania relapse is predicted by mood-incongruent psychosis – a condition usually associated with schizophrenia, he said.
“If [they] have unusual beliefs and ideas, and they’re not consistent with a particular mood state, we sometimes clinically think this sounds more like a primary psychotic process,” he said. “Maybe, but not necessarily. So just because the patient may say, ‘The FBI is after me,’ or, ‘My thoughts are being read over the Internet,’ and they don’t connect that with a grandiose theme, it doesn’t negate a diagnosis of bipolar disorder.”
Psychotic mania is also associated with comorbid anxiety disorder. About half of patients with bipolar I disorder will also experience impairments of attention, executive functioning, and verbal memory separately from ADHD. “The cognitive symptoms of bipolar disorder that are part of what’s inherited doesn’t seem to be the case, that there’s a clear greater degree of neuropsychological impairment in psychotic than nonpsychotic mania,” Dr. Goldberg said.
Lithium has a poor response in the presence of psychosis in patients with bipolar disorder but performs better when the patient receives it alongside an antipsychotic. “Lithium does have value in psychotic mania,” Dr. Goldberg said. “Psychosis would be a negative prognostic sign, and certainly an indication for including an antipsychotic.”
In contrast to lithium, divalproex has shown evidence in reducing manic and psychotic symptoms similarly to haloperidol. “Divalproex may reduce mania symptoms, whether or not it’s helping psychosis. You’d think you have to get both reduced at the same time, but actually can see that even if there’s baseline psychosis, that does not diminish the chance of seeing a reduction in core mania symptoms,” Dr. Goldberg said.
Carbamazepine may also be advantageous to use over lithium when patients present with delusions, and a combination of carbamazepine and lithium may be comparable to haloperidol in combination with lithium when treating psychotic mania. “What we do know is, at least in some studies, there may be some greater value in treating psychotic mania with carbamazepine as compared to lithium, particularly when there are delusions present, more so than hallucinations or formal thought disorder,” Dr. Goldberg said.
In patients with bipolar disorder and associated psychotic mania, clinicians should avoid dopamine agonists such as amphetamine and pramipexole, as well as ketamine. While some evidence has shown that second-generation antipsychotics work to treat bipolar depression, “there’s not really an evidence base to suggest that first-generation antipsychotics are protective against depression,” Dr. Goldberg said.
Bipolar disorder with anxiety
An association exists between comorbid anxiety disorders in patients with bipolar disorder and having a younger age of onset, in people who are less likely to recover from an initial mood episode, in people with poorer quality of life and role functioning, and in people who are less euthymic and more likely to attempt suicide, Dr. Goldberg said.
In addition, some patients may demonstrate symptoms of anxiety that aren’t part of the DSM-5 criteria for an anxiety disorder. Dr. Goldberg said he asks his patients to specify what they mean when they say they feel anxious.
“I always ask patients to tell me in very basic terms what [they] mean by anxiety. If they say, ‘I just I can’t sit still; I’m very fidgety,’ maybe that’s akathisia,” he said. “Or maybe if they say they’re very anxious, what they mean is they have so much energy they can’t contain it. This is mania or hypomania that they’re misconstruing as anxiety. We have to be very diligent and vigilant in clarifying the language here.”
To treat comorbid anxiety in patients with bipolar disorder, consider adjunctive olanzapine or lamotrigine, as both have evidence of anxiolytic efficacy. “Olanzapine does count as an antianxiety agent. Would you use it just as an antianxiety agent? Probably not in and of itself, but there’s other compelling reasons to use it,” he said. Before assuming you need to add another medication to address anxiety in a patient, “step back and think perhaps their anxiety symptoms will in themselves remit with olanzapine,” he said. , he added.
Divalproex is another option for patients that has anxiolytic efficacy. “In the context of bipolar depression, divalproex does have antianxiety properties,” Dr. Goldberg said. Other anxiolytic options include lurasidone, cariprazine, quetiapine, and combination olanzapine–fluoxetine.
Bipolar disorder and ADHD
Among patients with bipolar disorder and comorbid adult ADHD, cognitive dysfunction inherent to bipolar disorder may be difficult to distinguish from signs of ADHD, Dr. Goldberg explained, with about 20% of people with bipolar I disorder and about 30% of people with bipolar II disorder have deficits of attentional processing, verbal memory, and executive functioning.
“Some researchers are very intrigued by the notion that cognitive problems and attentional problems aren’t necessarily a sign of [ADHD] comorbidities. They might be, but they may just be part of the endophenotype or the non-overt, genetically driven phenomenology that makes bipolar disorder so heterogeneous,” he said.
Patients with bipolar disorder and comorbid ADHD are more likely to have mania than depression, the condition is more common in men, and these patients are more likely to have substance use problems, increased risk of suicide attempts, problems in school, lower socioeconomic status, greater unemployment history, higher divorce rates, and low family history of bipolar disorder. Clinicians should check a patient’s history if they suspect comorbid adult ADHD in their patients with bipolar disorder, as there is a good chance evidence of ADHD will be present around the time of adolescence.
“You don’t wake up with [ADHD] at age 40, at least that’s not the prevailing perspective,” Dr. Goldberg said.
Focus on the ADHD symptoms that do not overlap with bipolar disorder, such as nondiscrete, chronic symptoms; lack of psychosis and suicidality; no evidence of grandiose beliefs; lack of hypersexuality; and depression that is not prominent. “You really need to go back in time and get some clarity as to the longitudinal course. If this was present earlier on and it persists into adulthood and it’s not better accounted for by either what we think of as the cognitive pervasive problems that emerge in bipolar disorder, or in relatives as a collaborator for attentional problems and bipolar disorder, we can then contemplate [whether] there’s a plausible basis for using a stimulant or [other ADHD] treatment,” he said.
In patients who are found to have adult comorbid ADHD and are nonmanic and nonpsychotic, stimulants do have an effect. Studies suggest that amphetamines such as adjunctive lisdexamfetamine added to a mood stabilizer show an improvement in ADHD symptoms after 4 weeks (Hum Psychopharmacol. 2013; 28[5]:421-7).
Adjunctive methylphenidate added to a mood stabilizer has also shown evidence of not causing treatment-emergent mania. “If you’re going to use methylphenidate, make sure it’s in the context of an antimanic mood stabilizer,” Dr. Goldberg said. In one study, methylphenidate without a mood stabilizer caused an increase in manic episodes within 3 months (Am J Psychiatry. 2017 Apr 1;174:341-8).
“All may pose safe and effective evidence-based, albeit provisional, but evidence-based options to consider in targeting the attentional symptoms in patients with bipolar disorder,” Dr. Goldberg said.
He reported that he has been a consultant for BioXcel Therapeutics, Medscape/WebMD, Otsuka, and Sage Therapeutics. In addition, Dr. Goldberg is on the speakers bureau for Allergan, Neurocrine, Otsuka, and Sunovion; and receives royalties from American Psychiatric Publishing. Global Academy and this news organization are owned by the same parent company.
When selecting pharmacotherapy for patients with bipolar disorder, clinical and prognostic correlates will ultimately influence what treatments make the most sense for a patient – but the process is a balancing act, according to Joseph F. Goldberg, MD.
“Everything we do in medicine in general, and psychiatry, and bipolar disorder in particular is a risk-benefit analysis,” Dr. Goldberg said at the virtual Psychopharmacology Update presented by Current Psychiatry and Global Academy for Medical Education. “Everything has its side effects. We’re always balancing risks and benefits.”
Patients with bipolar disorder often present with three common subtypes of the illness: Those who have associated psychosis, comorbid anxiety disorders, and comorbid ADHD. “These are three common presentations of the many, many kinds of presentations,” said Dr. Goldberg, clinical professor of psychiatry at the Icahn School of Medicine at Mount Sinai in New York.
Bipolar disorder with associated psychosis
In the case of bipolar I disorder, more than 50% of manic episodes have some element of psychosis, with as many as 10% of patients showing signs of delusions 2 years after an episode, Dr. Goldberg explained. In these patients, mania relapse is predicted by mood-incongruent psychosis – a condition usually associated with schizophrenia, he said.
“If [they] have unusual beliefs and ideas, and they’re not consistent with a particular mood state, we sometimes clinically think this sounds more like a primary psychotic process,” he said. “Maybe, but not necessarily. So just because the patient may say, ‘The FBI is after me,’ or, ‘My thoughts are being read over the Internet,’ and they don’t connect that with a grandiose theme, it doesn’t negate a diagnosis of bipolar disorder.”
Psychotic mania is also associated with comorbid anxiety disorder. About half of patients with bipolar I disorder will also experience impairments of attention, executive functioning, and verbal memory separately from ADHD. “The cognitive symptoms of bipolar disorder that are part of what’s inherited doesn’t seem to be the case, that there’s a clear greater degree of neuropsychological impairment in psychotic than nonpsychotic mania,” Dr. Goldberg said.
Lithium has a poor response in the presence of psychosis in patients with bipolar disorder but performs better when the patient receives it alongside an antipsychotic. “Lithium does have value in psychotic mania,” Dr. Goldberg said. “Psychosis would be a negative prognostic sign, and certainly an indication for including an antipsychotic.”
In contrast to lithium, divalproex has shown evidence in reducing manic and psychotic symptoms similarly to haloperidol. “Divalproex may reduce mania symptoms, whether or not it’s helping psychosis. You’d think you have to get both reduced at the same time, but actually can see that even if there’s baseline psychosis, that does not diminish the chance of seeing a reduction in core mania symptoms,” Dr. Goldberg said.
Carbamazepine may also be advantageous to use over lithium when patients present with delusions, and a combination of carbamazepine and lithium may be comparable to haloperidol in combination with lithium when treating psychotic mania. “What we do know is, at least in some studies, there may be some greater value in treating psychotic mania with carbamazepine as compared to lithium, particularly when there are delusions present, more so than hallucinations or formal thought disorder,” Dr. Goldberg said.
In patients with bipolar disorder and associated psychotic mania, clinicians should avoid dopamine agonists such as amphetamine and pramipexole, as well as ketamine. While some evidence has shown that second-generation antipsychotics work to treat bipolar depression, “there’s not really an evidence base to suggest that first-generation antipsychotics are protective against depression,” Dr. Goldberg said.
Bipolar disorder with anxiety
An association exists between comorbid anxiety disorders in patients with bipolar disorder and having a younger age of onset, in people who are less likely to recover from an initial mood episode, in people with poorer quality of life and role functioning, and in people who are less euthymic and more likely to attempt suicide, Dr. Goldberg said.
In addition, some patients may demonstrate symptoms of anxiety that aren’t part of the DSM-5 criteria for an anxiety disorder. Dr. Goldberg said he asks his patients to specify what they mean when they say they feel anxious.
“I always ask patients to tell me in very basic terms what [they] mean by anxiety. If they say, ‘I just I can’t sit still; I’m very fidgety,’ maybe that’s akathisia,” he said. “Or maybe if they say they’re very anxious, what they mean is they have so much energy they can’t contain it. This is mania or hypomania that they’re misconstruing as anxiety. We have to be very diligent and vigilant in clarifying the language here.”
To treat comorbid anxiety in patients with bipolar disorder, consider adjunctive olanzapine or lamotrigine, as both have evidence of anxiolytic efficacy. “Olanzapine does count as an antianxiety agent. Would you use it just as an antianxiety agent? Probably not in and of itself, but there’s other compelling reasons to use it,” he said. Before assuming you need to add another medication to address anxiety in a patient, “step back and think perhaps their anxiety symptoms will in themselves remit with olanzapine,” he said. , he added.
Divalproex is another option for patients that has anxiolytic efficacy. “In the context of bipolar depression, divalproex does have antianxiety properties,” Dr. Goldberg said. Other anxiolytic options include lurasidone, cariprazine, quetiapine, and combination olanzapine–fluoxetine.
Bipolar disorder and ADHD
Among patients with bipolar disorder and comorbid adult ADHD, cognitive dysfunction inherent to bipolar disorder may be difficult to distinguish from signs of ADHD, Dr. Goldberg explained, with about 20% of people with bipolar I disorder and about 30% of people with bipolar II disorder have deficits of attentional processing, verbal memory, and executive functioning.
“Some researchers are very intrigued by the notion that cognitive problems and attentional problems aren’t necessarily a sign of [ADHD] comorbidities. They might be, but they may just be part of the endophenotype or the non-overt, genetically driven phenomenology that makes bipolar disorder so heterogeneous,” he said.
Patients with bipolar disorder and comorbid ADHD are more likely to have mania than depression, the condition is more common in men, and these patients are more likely to have substance use problems, increased risk of suicide attempts, problems in school, lower socioeconomic status, greater unemployment history, higher divorce rates, and low family history of bipolar disorder. Clinicians should check a patient’s history if they suspect comorbid adult ADHD in their patients with bipolar disorder, as there is a good chance evidence of ADHD will be present around the time of adolescence.
“You don’t wake up with [ADHD] at age 40, at least that’s not the prevailing perspective,” Dr. Goldberg said.
Focus on the ADHD symptoms that do not overlap with bipolar disorder, such as nondiscrete, chronic symptoms; lack of psychosis and suicidality; no evidence of grandiose beliefs; lack of hypersexuality; and depression that is not prominent. “You really need to go back in time and get some clarity as to the longitudinal course. If this was present earlier on and it persists into adulthood and it’s not better accounted for by either what we think of as the cognitive pervasive problems that emerge in bipolar disorder, or in relatives as a collaborator for attentional problems and bipolar disorder, we can then contemplate [whether] there’s a plausible basis for using a stimulant or [other ADHD] treatment,” he said.
In patients who are found to have adult comorbid ADHD and are nonmanic and nonpsychotic, stimulants do have an effect. Studies suggest that amphetamines such as adjunctive lisdexamfetamine added to a mood stabilizer show an improvement in ADHD symptoms after 4 weeks (Hum Psychopharmacol. 2013; 28[5]:421-7).
Adjunctive methylphenidate added to a mood stabilizer has also shown evidence of not causing treatment-emergent mania. “If you’re going to use methylphenidate, make sure it’s in the context of an antimanic mood stabilizer,” Dr. Goldberg said. In one study, methylphenidate without a mood stabilizer caused an increase in manic episodes within 3 months (Am J Psychiatry. 2017 Apr 1;174:341-8).
“All may pose safe and effective evidence-based, albeit provisional, but evidence-based options to consider in targeting the attentional symptoms in patients with bipolar disorder,” Dr. Goldberg said.
He reported that he has been a consultant for BioXcel Therapeutics, Medscape/WebMD, Otsuka, and Sage Therapeutics. In addition, Dr. Goldberg is on the speakers bureau for Allergan, Neurocrine, Otsuka, and Sunovion; and receives royalties from American Psychiatric Publishing. Global Academy and this news organization are owned by the same parent company.
When selecting pharmacotherapy for patients with bipolar disorder, clinical and prognostic correlates will ultimately influence what treatments make the most sense for a patient – but the process is a balancing act, according to Joseph F. Goldberg, MD.
“Everything we do in medicine in general, and psychiatry, and bipolar disorder in particular is a risk-benefit analysis,” Dr. Goldberg said at the virtual Psychopharmacology Update presented by Current Psychiatry and Global Academy for Medical Education. “Everything has its side effects. We’re always balancing risks and benefits.”
Patients with bipolar disorder often present with three common subtypes of the illness: Those who have associated psychosis, comorbid anxiety disorders, and comorbid ADHD. “These are three common presentations of the many, many kinds of presentations,” said Dr. Goldberg, clinical professor of psychiatry at the Icahn School of Medicine at Mount Sinai in New York.
Bipolar disorder with associated psychosis
In the case of bipolar I disorder, more than 50% of manic episodes have some element of psychosis, with as many as 10% of patients showing signs of delusions 2 years after an episode, Dr. Goldberg explained. In these patients, mania relapse is predicted by mood-incongruent psychosis – a condition usually associated with schizophrenia, he said.
“If [they] have unusual beliefs and ideas, and they’re not consistent with a particular mood state, we sometimes clinically think this sounds more like a primary psychotic process,” he said. “Maybe, but not necessarily. So just because the patient may say, ‘The FBI is after me,’ or, ‘My thoughts are being read over the Internet,’ and they don’t connect that with a grandiose theme, it doesn’t negate a diagnosis of bipolar disorder.”
Psychotic mania is also associated with comorbid anxiety disorder. About half of patients with bipolar I disorder will also experience impairments of attention, executive functioning, and verbal memory separately from ADHD. “The cognitive symptoms of bipolar disorder that are part of what’s inherited doesn’t seem to be the case, that there’s a clear greater degree of neuropsychological impairment in psychotic than nonpsychotic mania,” Dr. Goldberg said.
Lithium has a poor response in the presence of psychosis in patients with bipolar disorder but performs better when the patient receives it alongside an antipsychotic. “Lithium does have value in psychotic mania,” Dr. Goldberg said. “Psychosis would be a negative prognostic sign, and certainly an indication for including an antipsychotic.”
In contrast to lithium, divalproex has shown evidence in reducing manic and psychotic symptoms similarly to haloperidol. “Divalproex may reduce mania symptoms, whether or not it’s helping psychosis. You’d think you have to get both reduced at the same time, but actually can see that even if there’s baseline psychosis, that does not diminish the chance of seeing a reduction in core mania symptoms,” Dr. Goldberg said.
Carbamazepine may also be advantageous to use over lithium when patients present with delusions, and a combination of carbamazepine and lithium may be comparable to haloperidol in combination with lithium when treating psychotic mania. “What we do know is, at least in some studies, there may be some greater value in treating psychotic mania with carbamazepine as compared to lithium, particularly when there are delusions present, more so than hallucinations or formal thought disorder,” Dr. Goldberg said.
In patients with bipolar disorder and associated psychotic mania, clinicians should avoid dopamine agonists such as amphetamine and pramipexole, as well as ketamine. While some evidence has shown that second-generation antipsychotics work to treat bipolar depression, “there’s not really an evidence base to suggest that first-generation antipsychotics are protective against depression,” Dr. Goldberg said.
Bipolar disorder with anxiety
An association exists between comorbid anxiety disorders in patients with bipolar disorder and having a younger age of onset, in people who are less likely to recover from an initial mood episode, in people with poorer quality of life and role functioning, and in people who are less euthymic and more likely to attempt suicide, Dr. Goldberg said.
In addition, some patients may demonstrate symptoms of anxiety that aren’t part of the DSM-5 criteria for an anxiety disorder. Dr. Goldberg said he asks his patients to specify what they mean when they say they feel anxious.
“I always ask patients to tell me in very basic terms what [they] mean by anxiety. If they say, ‘I just I can’t sit still; I’m very fidgety,’ maybe that’s akathisia,” he said. “Or maybe if they say they’re very anxious, what they mean is they have so much energy they can’t contain it. This is mania or hypomania that they’re misconstruing as anxiety. We have to be very diligent and vigilant in clarifying the language here.”
To treat comorbid anxiety in patients with bipolar disorder, consider adjunctive olanzapine or lamotrigine, as both have evidence of anxiolytic efficacy. “Olanzapine does count as an antianxiety agent. Would you use it just as an antianxiety agent? Probably not in and of itself, but there’s other compelling reasons to use it,” he said. Before assuming you need to add another medication to address anxiety in a patient, “step back and think perhaps their anxiety symptoms will in themselves remit with olanzapine,” he said. , he added.
Divalproex is another option for patients that has anxiolytic efficacy. “In the context of bipolar depression, divalproex does have antianxiety properties,” Dr. Goldberg said. Other anxiolytic options include lurasidone, cariprazine, quetiapine, and combination olanzapine–fluoxetine.
Bipolar disorder and ADHD
Among patients with bipolar disorder and comorbid adult ADHD, cognitive dysfunction inherent to bipolar disorder may be difficult to distinguish from signs of ADHD, Dr. Goldberg explained, with about 20% of people with bipolar I disorder and about 30% of people with bipolar II disorder have deficits of attentional processing, verbal memory, and executive functioning.
“Some researchers are very intrigued by the notion that cognitive problems and attentional problems aren’t necessarily a sign of [ADHD] comorbidities. They might be, but they may just be part of the endophenotype or the non-overt, genetically driven phenomenology that makes bipolar disorder so heterogeneous,” he said.
Patients with bipolar disorder and comorbid ADHD are more likely to have mania than depression, the condition is more common in men, and these patients are more likely to have substance use problems, increased risk of suicide attempts, problems in school, lower socioeconomic status, greater unemployment history, higher divorce rates, and low family history of bipolar disorder. Clinicians should check a patient’s history if they suspect comorbid adult ADHD in their patients with bipolar disorder, as there is a good chance evidence of ADHD will be present around the time of adolescence.
“You don’t wake up with [ADHD] at age 40, at least that’s not the prevailing perspective,” Dr. Goldberg said.
Focus on the ADHD symptoms that do not overlap with bipolar disorder, such as nondiscrete, chronic symptoms; lack of psychosis and suicidality; no evidence of grandiose beliefs; lack of hypersexuality; and depression that is not prominent. “You really need to go back in time and get some clarity as to the longitudinal course. If this was present earlier on and it persists into adulthood and it’s not better accounted for by either what we think of as the cognitive pervasive problems that emerge in bipolar disorder, or in relatives as a collaborator for attentional problems and bipolar disorder, we can then contemplate [whether] there’s a plausible basis for using a stimulant or [other ADHD] treatment,” he said.
In patients who are found to have adult comorbid ADHD and are nonmanic and nonpsychotic, stimulants do have an effect. Studies suggest that amphetamines such as adjunctive lisdexamfetamine added to a mood stabilizer show an improvement in ADHD symptoms after 4 weeks (Hum Psychopharmacol. 2013; 28[5]:421-7).
Adjunctive methylphenidate added to a mood stabilizer has also shown evidence of not causing treatment-emergent mania. “If you’re going to use methylphenidate, make sure it’s in the context of an antimanic mood stabilizer,” Dr. Goldberg said. In one study, methylphenidate without a mood stabilizer caused an increase in manic episodes within 3 months (Am J Psychiatry. 2017 Apr 1;174:341-8).
“All may pose safe and effective evidence-based, albeit provisional, but evidence-based options to consider in targeting the attentional symptoms in patients with bipolar disorder,” Dr. Goldberg said.
He reported that he has been a consultant for BioXcel Therapeutics, Medscape/WebMD, Otsuka, and Sage Therapeutics. In addition, Dr. Goldberg is on the speakers bureau for Allergan, Neurocrine, Otsuka, and Sunovion; and receives royalties from American Psychiatric Publishing. Global Academy and this news organization are owned by the same parent company.
FROM PSYCHOPHARMACOLOGY UPDATE
Let side effects guide treatment choice for refractory OCD
Choosing the most effective treatment for patients with obsessive-compulsive disorder requires flexibility and agility on the part of clinicians, according to Wayne K. Goodman, MD.
“There are no data at this point to suggest that one SSRI is superior to another. It’s really dealer’s choice, and it has to do with really picking medications based upon side effects,” Dr. Goodman said at the Psychopharmacology Update, presented by Current Psychiatry and Global Academy for Medical Education. Clinicians can use family history as a guide, he noted, but pharmacogenetic testing has not been helpful in his experience for selection or dosing of an SSRI.
SSRIs, such as fluvoxamine, are one of two mainstays of treatment for patients with obsessive-compulsive disorder (OCD). The other drug class is serotonin reuptake inhibitors, which include medications such clomipramine. Cognitive-behavioral therapy options, such as Exposure and Response Prevention therapy, also has some, albeit limited, efficacy.
Meanwhile, Dr. Goodman said, antidepressant classes other than SRIs and SSRIs have not been effective in treating obsessive-compulsive symptoms, and some patients do not adhere well to cognitive-behavioral therapy, said Dr. Goodman, who is the D.C. and Irene Ellwood Professor in the department of psychiatry and behavioral sciences at Baylor College of Medicine, Houston.
Choosing the most effective treatment for patients with obsessive-compulsive disorder requires flexibility and agility on the part of clinicians, according to Wayne K. Goodman, MD.
“There are no data at this point to suggest that one SSRI is superior to another. It’s really dealer’s choice, and it has to do with really picking medications based upon side effects,” Dr. Goodman said at the Psychopharmacology Update, presented by Current Psychiatry and Global Academy for Medical Education. Clinicians can use family history as a guide, he noted, but pharmacogenetic testing has not been helpful in his experience for selection or dosing of an SSRI.
SSRIs, such as fluvoxamine, are one of two mainstays of treatment for patients with obsessive-compulsive disorder (OCD). The other drug class is serotonin reuptake inhibitors, which include medications such clomipramine. Cognitive-behavioral therapy options, such as Exposure and Response Prevention therapy, also has some, albeit limited, efficacy.
Meanwhile, Dr. Goodman said, antidepressant classes other than SRIs and SSRIs have not been effective in treating obsessive-compulsive symptoms, and some patients do not adhere well to cognitive-behavioral therapy, said Dr. Goodman, who is the D.C. and Irene Ellwood Professor in the department of psychiatry and behavioral sciences at Baylor College of Medicine, Houston.
Choosing the most effective treatment for patients with obsessive-compulsive disorder requires flexibility and agility on the part of clinicians, according to Wayne K. Goodman, MD.
“There are no data at this point to suggest that one SSRI is superior to another. It’s really dealer’s choice, and it has to do with really picking medications based upon side effects,” Dr. Goodman said at the Psychopharmacology Update, presented by Current Psychiatry and Global Academy for Medical Education. Clinicians can use family history as a guide, he noted, but pharmacogenetic testing has not been helpful in his experience for selection or dosing of an SSRI.
SSRIs, such as fluvoxamine, are one of two mainstays of treatment for patients with obsessive-compulsive disorder (OCD). The other drug class is serotonin reuptake inhibitors, which include medications such clomipramine. Cognitive-behavioral therapy options, such as Exposure and Response Prevention therapy, also has some, albeit limited, efficacy.
Meanwhile, Dr. Goodman said, antidepressant classes other than SRIs and SSRIs have not been effective in treating obsessive-compulsive symptoms, and some patients do not adhere well to cognitive-behavioral therapy, said Dr. Goodman, who is the D.C. and Irene Ellwood Professor in the department of psychiatry and behavioral sciences at Baylor College of Medicine, Houston.
FROM PSYCHOPHARMACOLOGY UPDATE
Decide ADHD pharmacotherapy based on medication onset, duration of action
Clinicians have numerous pharmacotherapy options available to treat ADHD in their toolbox. How do you know which formulation or combination of therapies is right for your patient with ADHD?
According to Jeffrey R. Strawn, MD, the answer depends on onset and duration of the medication and how that fits in to the patient’s current needs.
The most common treatment for ADHD, stimulants, are amphetamine-based and methylphenidate-based compounds known for improving core symptoms of inattention, impulsivity, and hyperactivity and are “probably associated with the most efficacy relative to the other interventions,” Dr. Strawn, associate professor of psychiatry, pediatrics, and clinical pharmacology at Cincinnati Children’s Hospital Medical Center, said at Psychopharmacology Update presented by Current Psychiatry and Global Academy for Medical Education. “But what I think is also really important for us to remember as clinicians is that they improve adherence, social interactions, [and] academic efficiency as well as accuracy.”
Other ADHD pharmacotherapy options include nonstimulant norepinephrine reuptake inhibitors (NRIs) like atomoxetine, and alpha-2 agonists like the extended-release forms of guanfacine and clonidine. All are Food and Drug Administration–approved for the treatment of ADHD, and the FDA has approved some combination alpha-2 agonists and stimulants treatments for ADHD as well.
When making decisions about formulations for ADHD pharmacotherapy, clinicians should think about whether the patient has issues swallowing tablets or capsules. Tablets, capsules, and chewable tablets may be appropriate for patients who can easily take these medications, while patients who have problems with swallowing pills may benefit from dissolvable tablets, solutions, and transdermal applications. Each of these options “have differences in terms of absorption, also differences in terms of intestinal transit time in younger children, as well as patients perhaps with irritable bowel, as well as other conditions that may affect absorption,” Dr. Strawn said. Different formulations have unique considerations: liquid formulations have the benefit of making precise adjustments, sublingual formulations may have quick absorption and onset, and oral dissolvable tablets can improve treatment adherence and reduce misuse of medication.
Formulations can be available as a delayed release, extended release, pulsatile release, targeted release, or a combination of immediate, delayed, and/or extended release. “Ultimately, what this gives rise to is differences in onset of action and duration, as well as differences in the elimination profile of the medication,” he said.
Transdermal formulations “avoid the first-pass metabolism, which may reduce side effects or increase efficacy,” but patients converting from an oral formulation may require reducing the dose. “It’s always important to remember, for example, with something like Daytrana, the transdermal methylphenidate formulation, if we’re converting a patient from an oral methylphenidate, we roughly need to use half the dose for the transdermal formulation,” Dr. Strawn explained. Transdermal formulations can carry benefits of steady plasma concentrations and longer duration of action but may cause skin irritation or accidentally be removed. “It’s really important they’re properly disposed of because oftentimes they do contain some active medication within the residual matrix.”
Methylphenidate, mixed amphetamine salt–based preparations
Modified-release formulations include matrix- or reservoir-based formulations and are most importantly differentiated from other formulations by their gastrointestinal (GI) transit time and the permeation through the GI membrane. When considering what formulation to choose, “it’s important to consider that, even with an ‘extended release formulation,’ all of these medications have some percentage that is immediately released, and that percentage varies considerably from formulation to formulation,” Dr. Strawn said.
He noted that brand names are sometimes used for formulations “because it’s often very difficult for us as clinicians and even for pharmacists to distinguish between these various formulations of the medication, which often have the same ‘extended’ or ‘delayed release’ modifying term within the name of the medication.”
Examples of medications that have greater immediate release include Metadate CD (30%), Aptensio XR (37%), long-acting methylphenidate (50%), dexmethylphenidate extended-release (50%), and Mixed Salts amphetamine extended release (50%). Formulations with a less immediate release include Quillivant solution or Quillichew chewable tablets (20%), Dyanaval XR solution (20%), OROS methylphenidate (22%), Daytrana that begins within 1 or 2 hours and lasts for 9 hours, or lisdexamfetamine that begins within 1 hour and lasts for 9 hours.
Depending on a patient’s needs, one particular formulation may work better than another. Dexmethylphenidate (Focalin XR) has a 50% immediate release and 50% extended release formulation, which “may be really important for a high school student who has first period precalculus followed by second period human geography,” Dr. Strawn said, while “a patient who may have first period study hall and second period art” may benefit from OROS methylphenidate.
Clinicians should also consider the effect of counterclockwise hysteresis when adding a short-acting stimulant later in the day. “There seems to be something really magic about having that ascending concentration time curve that, when we’re on the descending loop of that concentration time curve, we really seem to get a dramatic waning of the effect of the medication, even though technically the concentration is within the ‘therapeutic range,’ ” Dr. Strawn said. “With counterclockwise hysteresis, we see that the effect increases with time for a given concentration of the medication.”
Combining ADHD pharmacotherapies
For children and adolescents with ADHD, atomoxetine is a nonstimulant, FDA-approved treatment option. “It seems to be effective not just in terms of total ADHD symptoms, but also in terms of hyperactive and impulsive symptoms as well as the inattentive symptoms,” Dr. Strawn said.
Pharmacogenetics can be a guide for selecting an atomoxetine for a patient with ADHD, he noted. “What I think is most relevant here is the way in which pharmacogenetics can actually help guide our dosing, which then optimizes tolerability, potentially efficacy of atomoxetine,” he said. “Atomoxetine is pretty extensively metabolized by [CYP]2D6, and it’s one of about 300 medications that actually has specific labeling from the FDA on dosing based on genotype. It recommends a slower titration, as well as a lower target dose of atomoxetine in individuals who are P450 2D6 poor metabolizers relative to those patients who are ultra-rapid or normal metabolizers.”
Atomoxetine is most often combined with methylphenidate and has some evidence of benefit in children or adolescents who do not have an adequate response to stimulants alone. When combining stimulants with the alpha-2 agonists guanfacine or clonidine, “there are some improvements in terms of the combination treatment relative to the monotherapy,” Dr. Strawn said. He also emphasized that patients taking guanfacine immediate release tend to have better absorption and faster onset, compared with the extended release formulation. “This is something that potentially is very important when we think beyond steady state and we think about the practical use of this medication,” he said.
Baseline history is important
Overall, taking a baseline history of a patient with ADHD is “critically important” before starting them on stimulants, Dr. Strawn said. “Specifically, I would recommend documenting a negative history of syncope, family history of sudden cardiac death, as well as the lack of any known history of structural cardiac abnormalities,” he said. “Without a consultation with the cardiologist specifically around this question, I’m very, very, very hesitant – as in I don’t – use stimulants in patients who have histories of aortic stenosis, Wolff-Parkinson-White, as well as arrhythmogenic right ventricular dysplasia.”
Although patients with ADHD were typically followed with routine hemodynamic monitoring every 3 months prior to the COVID-19 pandemic, some clinicians see their patients with ADHD less frequently if they have been stabilized on a stimulant. , particularly in young children. In adults, it may also be very helpful to talk with spouses,” Dr. Strawn said.
Dr. Strawn also called attention to a recommendation to perform a routine electrocardiogram (EKG) in patients with ADHD who might receive stimulants. “At present, there is no recommendation to obtain a routine screening EKG in these patients, provided that we have an absence of those other red flags on the history,” he said. “Certainly, I would consider it in situations where I do have persistent tachycardia or hypertension, or there are other treatment-emergent symptoms, although really in many of these situations, I’m actually speaking on the phone with my pediatric or adult cardiology colleagues.”
Global Academy and this news organization are owned by the same parent company. Dr. Strawn reported receiving research support from Allergan, the FDA, the National Institutes of Health, Neuronetics, and Otsuka; serving as a consultant and receiving material support from Myriad; receiving royalties from Springer Publishing; and serving as a consultant for Intra-Cellular Therapies. In addition, he has been on the speaker’s bureau for the Neuroscience Education Institute and CMEology, and Medscape.
Clinicians have numerous pharmacotherapy options available to treat ADHD in their toolbox. How do you know which formulation or combination of therapies is right for your patient with ADHD?
According to Jeffrey R. Strawn, MD, the answer depends on onset and duration of the medication and how that fits in to the patient’s current needs.
The most common treatment for ADHD, stimulants, are amphetamine-based and methylphenidate-based compounds known for improving core symptoms of inattention, impulsivity, and hyperactivity and are “probably associated with the most efficacy relative to the other interventions,” Dr. Strawn, associate professor of psychiatry, pediatrics, and clinical pharmacology at Cincinnati Children’s Hospital Medical Center, said at Psychopharmacology Update presented by Current Psychiatry and Global Academy for Medical Education. “But what I think is also really important for us to remember as clinicians is that they improve adherence, social interactions, [and] academic efficiency as well as accuracy.”
Other ADHD pharmacotherapy options include nonstimulant norepinephrine reuptake inhibitors (NRIs) like atomoxetine, and alpha-2 agonists like the extended-release forms of guanfacine and clonidine. All are Food and Drug Administration–approved for the treatment of ADHD, and the FDA has approved some combination alpha-2 agonists and stimulants treatments for ADHD as well.
When making decisions about formulations for ADHD pharmacotherapy, clinicians should think about whether the patient has issues swallowing tablets or capsules. Tablets, capsules, and chewable tablets may be appropriate for patients who can easily take these medications, while patients who have problems with swallowing pills may benefit from dissolvable tablets, solutions, and transdermal applications. Each of these options “have differences in terms of absorption, also differences in terms of intestinal transit time in younger children, as well as patients perhaps with irritable bowel, as well as other conditions that may affect absorption,” Dr. Strawn said. Different formulations have unique considerations: liquid formulations have the benefit of making precise adjustments, sublingual formulations may have quick absorption and onset, and oral dissolvable tablets can improve treatment adherence and reduce misuse of medication.
Formulations can be available as a delayed release, extended release, pulsatile release, targeted release, or a combination of immediate, delayed, and/or extended release. “Ultimately, what this gives rise to is differences in onset of action and duration, as well as differences in the elimination profile of the medication,” he said.
Transdermal formulations “avoid the first-pass metabolism, which may reduce side effects or increase efficacy,” but patients converting from an oral formulation may require reducing the dose. “It’s always important to remember, for example, with something like Daytrana, the transdermal methylphenidate formulation, if we’re converting a patient from an oral methylphenidate, we roughly need to use half the dose for the transdermal formulation,” Dr. Strawn explained. Transdermal formulations can carry benefits of steady plasma concentrations and longer duration of action but may cause skin irritation or accidentally be removed. “It’s really important they’re properly disposed of because oftentimes they do contain some active medication within the residual matrix.”
Methylphenidate, mixed amphetamine salt–based preparations
Modified-release formulations include matrix- or reservoir-based formulations and are most importantly differentiated from other formulations by their gastrointestinal (GI) transit time and the permeation through the GI membrane. When considering what formulation to choose, “it’s important to consider that, even with an ‘extended release formulation,’ all of these medications have some percentage that is immediately released, and that percentage varies considerably from formulation to formulation,” Dr. Strawn said.
He noted that brand names are sometimes used for formulations “because it’s often very difficult for us as clinicians and even for pharmacists to distinguish between these various formulations of the medication, which often have the same ‘extended’ or ‘delayed release’ modifying term within the name of the medication.”
Examples of medications that have greater immediate release include Metadate CD (30%), Aptensio XR (37%), long-acting methylphenidate (50%), dexmethylphenidate extended-release (50%), and Mixed Salts amphetamine extended release (50%). Formulations with a less immediate release include Quillivant solution or Quillichew chewable tablets (20%), Dyanaval XR solution (20%), OROS methylphenidate (22%), Daytrana that begins within 1 or 2 hours and lasts for 9 hours, or lisdexamfetamine that begins within 1 hour and lasts for 9 hours.
Depending on a patient’s needs, one particular formulation may work better than another. Dexmethylphenidate (Focalin XR) has a 50% immediate release and 50% extended release formulation, which “may be really important for a high school student who has first period precalculus followed by second period human geography,” Dr. Strawn said, while “a patient who may have first period study hall and second period art” may benefit from OROS methylphenidate.
Clinicians should also consider the effect of counterclockwise hysteresis when adding a short-acting stimulant later in the day. “There seems to be something really magic about having that ascending concentration time curve that, when we’re on the descending loop of that concentration time curve, we really seem to get a dramatic waning of the effect of the medication, even though technically the concentration is within the ‘therapeutic range,’ ” Dr. Strawn said. “With counterclockwise hysteresis, we see that the effect increases with time for a given concentration of the medication.”
Combining ADHD pharmacotherapies
For children and adolescents with ADHD, atomoxetine is a nonstimulant, FDA-approved treatment option. “It seems to be effective not just in terms of total ADHD symptoms, but also in terms of hyperactive and impulsive symptoms as well as the inattentive symptoms,” Dr. Strawn said.
Pharmacogenetics can be a guide for selecting an atomoxetine for a patient with ADHD, he noted. “What I think is most relevant here is the way in which pharmacogenetics can actually help guide our dosing, which then optimizes tolerability, potentially efficacy of atomoxetine,” he said. “Atomoxetine is pretty extensively metabolized by [CYP]2D6, and it’s one of about 300 medications that actually has specific labeling from the FDA on dosing based on genotype. It recommends a slower titration, as well as a lower target dose of atomoxetine in individuals who are P450 2D6 poor metabolizers relative to those patients who are ultra-rapid or normal metabolizers.”
Atomoxetine is most often combined with methylphenidate and has some evidence of benefit in children or adolescents who do not have an adequate response to stimulants alone. When combining stimulants with the alpha-2 agonists guanfacine or clonidine, “there are some improvements in terms of the combination treatment relative to the monotherapy,” Dr. Strawn said. He also emphasized that patients taking guanfacine immediate release tend to have better absorption and faster onset, compared with the extended release formulation. “This is something that potentially is very important when we think beyond steady state and we think about the practical use of this medication,” he said.
Baseline history is important
Overall, taking a baseline history of a patient with ADHD is “critically important” before starting them on stimulants, Dr. Strawn said. “Specifically, I would recommend documenting a negative history of syncope, family history of sudden cardiac death, as well as the lack of any known history of structural cardiac abnormalities,” he said. “Without a consultation with the cardiologist specifically around this question, I’m very, very, very hesitant – as in I don’t – use stimulants in patients who have histories of aortic stenosis, Wolff-Parkinson-White, as well as arrhythmogenic right ventricular dysplasia.”
Although patients with ADHD were typically followed with routine hemodynamic monitoring every 3 months prior to the COVID-19 pandemic, some clinicians see their patients with ADHD less frequently if they have been stabilized on a stimulant. , particularly in young children. In adults, it may also be very helpful to talk with spouses,” Dr. Strawn said.
Dr. Strawn also called attention to a recommendation to perform a routine electrocardiogram (EKG) in patients with ADHD who might receive stimulants. “At present, there is no recommendation to obtain a routine screening EKG in these patients, provided that we have an absence of those other red flags on the history,” he said. “Certainly, I would consider it in situations where I do have persistent tachycardia or hypertension, or there are other treatment-emergent symptoms, although really in many of these situations, I’m actually speaking on the phone with my pediatric or adult cardiology colleagues.”
Global Academy and this news organization are owned by the same parent company. Dr. Strawn reported receiving research support from Allergan, the FDA, the National Institutes of Health, Neuronetics, and Otsuka; serving as a consultant and receiving material support from Myriad; receiving royalties from Springer Publishing; and serving as a consultant for Intra-Cellular Therapies. In addition, he has been on the speaker’s bureau for the Neuroscience Education Institute and CMEology, and Medscape.
Clinicians have numerous pharmacotherapy options available to treat ADHD in their toolbox. How do you know which formulation or combination of therapies is right for your patient with ADHD?
According to Jeffrey R. Strawn, MD, the answer depends on onset and duration of the medication and how that fits in to the patient’s current needs.
The most common treatment for ADHD, stimulants, are amphetamine-based and methylphenidate-based compounds known for improving core symptoms of inattention, impulsivity, and hyperactivity and are “probably associated with the most efficacy relative to the other interventions,” Dr. Strawn, associate professor of psychiatry, pediatrics, and clinical pharmacology at Cincinnati Children’s Hospital Medical Center, said at Psychopharmacology Update presented by Current Psychiatry and Global Academy for Medical Education. “But what I think is also really important for us to remember as clinicians is that they improve adherence, social interactions, [and] academic efficiency as well as accuracy.”
Other ADHD pharmacotherapy options include nonstimulant norepinephrine reuptake inhibitors (NRIs) like atomoxetine, and alpha-2 agonists like the extended-release forms of guanfacine and clonidine. All are Food and Drug Administration–approved for the treatment of ADHD, and the FDA has approved some combination alpha-2 agonists and stimulants treatments for ADHD as well.
When making decisions about formulations for ADHD pharmacotherapy, clinicians should think about whether the patient has issues swallowing tablets or capsules. Tablets, capsules, and chewable tablets may be appropriate for patients who can easily take these medications, while patients who have problems with swallowing pills may benefit from dissolvable tablets, solutions, and transdermal applications. Each of these options “have differences in terms of absorption, also differences in terms of intestinal transit time in younger children, as well as patients perhaps with irritable bowel, as well as other conditions that may affect absorption,” Dr. Strawn said. Different formulations have unique considerations: liquid formulations have the benefit of making precise adjustments, sublingual formulations may have quick absorption and onset, and oral dissolvable tablets can improve treatment adherence and reduce misuse of medication.
Formulations can be available as a delayed release, extended release, pulsatile release, targeted release, or a combination of immediate, delayed, and/or extended release. “Ultimately, what this gives rise to is differences in onset of action and duration, as well as differences in the elimination profile of the medication,” he said.
Transdermal formulations “avoid the first-pass metabolism, which may reduce side effects or increase efficacy,” but patients converting from an oral formulation may require reducing the dose. “It’s always important to remember, for example, with something like Daytrana, the transdermal methylphenidate formulation, if we’re converting a patient from an oral methylphenidate, we roughly need to use half the dose for the transdermal formulation,” Dr. Strawn explained. Transdermal formulations can carry benefits of steady plasma concentrations and longer duration of action but may cause skin irritation or accidentally be removed. “It’s really important they’re properly disposed of because oftentimes they do contain some active medication within the residual matrix.”
Methylphenidate, mixed amphetamine salt–based preparations
Modified-release formulations include matrix- or reservoir-based formulations and are most importantly differentiated from other formulations by their gastrointestinal (GI) transit time and the permeation through the GI membrane. When considering what formulation to choose, “it’s important to consider that, even with an ‘extended release formulation,’ all of these medications have some percentage that is immediately released, and that percentage varies considerably from formulation to formulation,” Dr. Strawn said.
He noted that brand names are sometimes used for formulations “because it’s often very difficult for us as clinicians and even for pharmacists to distinguish between these various formulations of the medication, which often have the same ‘extended’ or ‘delayed release’ modifying term within the name of the medication.”
Examples of medications that have greater immediate release include Metadate CD (30%), Aptensio XR (37%), long-acting methylphenidate (50%), dexmethylphenidate extended-release (50%), and Mixed Salts amphetamine extended release (50%). Formulations with a less immediate release include Quillivant solution or Quillichew chewable tablets (20%), Dyanaval XR solution (20%), OROS methylphenidate (22%), Daytrana that begins within 1 or 2 hours and lasts for 9 hours, or lisdexamfetamine that begins within 1 hour and lasts for 9 hours.
Depending on a patient’s needs, one particular formulation may work better than another. Dexmethylphenidate (Focalin XR) has a 50% immediate release and 50% extended release formulation, which “may be really important for a high school student who has first period precalculus followed by second period human geography,” Dr. Strawn said, while “a patient who may have first period study hall and second period art” may benefit from OROS methylphenidate.
Clinicians should also consider the effect of counterclockwise hysteresis when adding a short-acting stimulant later in the day. “There seems to be something really magic about having that ascending concentration time curve that, when we’re on the descending loop of that concentration time curve, we really seem to get a dramatic waning of the effect of the medication, even though technically the concentration is within the ‘therapeutic range,’ ” Dr. Strawn said. “With counterclockwise hysteresis, we see that the effect increases with time for a given concentration of the medication.”
Combining ADHD pharmacotherapies
For children and adolescents with ADHD, atomoxetine is a nonstimulant, FDA-approved treatment option. “It seems to be effective not just in terms of total ADHD symptoms, but also in terms of hyperactive and impulsive symptoms as well as the inattentive symptoms,” Dr. Strawn said.
Pharmacogenetics can be a guide for selecting an atomoxetine for a patient with ADHD, he noted. “What I think is most relevant here is the way in which pharmacogenetics can actually help guide our dosing, which then optimizes tolerability, potentially efficacy of atomoxetine,” he said. “Atomoxetine is pretty extensively metabolized by [CYP]2D6, and it’s one of about 300 medications that actually has specific labeling from the FDA on dosing based on genotype. It recommends a slower titration, as well as a lower target dose of atomoxetine in individuals who are P450 2D6 poor metabolizers relative to those patients who are ultra-rapid or normal metabolizers.”
Atomoxetine is most often combined with methylphenidate and has some evidence of benefit in children or adolescents who do not have an adequate response to stimulants alone. When combining stimulants with the alpha-2 agonists guanfacine or clonidine, “there are some improvements in terms of the combination treatment relative to the monotherapy,” Dr. Strawn said. He also emphasized that patients taking guanfacine immediate release tend to have better absorption and faster onset, compared with the extended release formulation. “This is something that potentially is very important when we think beyond steady state and we think about the practical use of this medication,” he said.
Baseline history is important
Overall, taking a baseline history of a patient with ADHD is “critically important” before starting them on stimulants, Dr. Strawn said. “Specifically, I would recommend documenting a negative history of syncope, family history of sudden cardiac death, as well as the lack of any known history of structural cardiac abnormalities,” he said. “Without a consultation with the cardiologist specifically around this question, I’m very, very, very hesitant – as in I don’t – use stimulants in patients who have histories of aortic stenosis, Wolff-Parkinson-White, as well as arrhythmogenic right ventricular dysplasia.”
Although patients with ADHD were typically followed with routine hemodynamic monitoring every 3 months prior to the COVID-19 pandemic, some clinicians see their patients with ADHD less frequently if they have been stabilized on a stimulant. , particularly in young children. In adults, it may also be very helpful to talk with spouses,” Dr. Strawn said.
Dr. Strawn also called attention to a recommendation to perform a routine electrocardiogram (EKG) in patients with ADHD who might receive stimulants. “At present, there is no recommendation to obtain a routine screening EKG in these patients, provided that we have an absence of those other red flags on the history,” he said. “Certainly, I would consider it in situations where I do have persistent tachycardia or hypertension, or there are other treatment-emergent symptoms, although really in many of these situations, I’m actually speaking on the phone with my pediatric or adult cardiology colleagues.”
Global Academy and this news organization are owned by the same parent company. Dr. Strawn reported receiving research support from Allergan, the FDA, the National Institutes of Health, Neuronetics, and Otsuka; serving as a consultant and receiving material support from Myriad; receiving royalties from Springer Publishing; and serving as a consultant for Intra-Cellular Therapies. In addition, he has been on the speaker’s bureau for the Neuroscience Education Institute and CMEology, and Medscape.
FROM PSYCHOPHARMACOLOGY UPDATE
HIT-6 may help track meaningful change in chronic migraine
, recent research suggests.
Using data from the phase 3 PROMISE-2 study, which evaluated intravenous eptinezumab in doses of 100 mg or 300 mg, or placebo every 12 weeks in 1,072 participants for the prevention of chronic migraine, Carrie R. Houts, PhD, director of psychometrics at the Vector Psychometric Group, in Chapel Hill, N.C., and colleagues determined that their finding of 6-point improvement of HIT-6 total score was consistent with other studies. However, they pointed out that little research has been done in evaluating how item-specific scores of HIT-6 impact individuals with chronic migraine. HIT-6 item scores examine whether individuals with headaches experience severe pain, limit their daily activities, have a desire to lie down, feel too tired to do daily activities, felt “fed up or irritated” because of headaches, and feel their headaches limit concentration on work or daily activities.
“The item-specific responder definitions give clinicians and researchers the ability to evaluate and track the impact of headache on specific item-level areas of patients’ lives. These responder definitions provide practical and easily interpreted results that can be used to evaluate treatment benefits over time and to improve clinician-patients communication focus on improvements in key aspects of functioning in individuals with chronic migraine,” Dr. Houts and colleagues wrote in their study, published in the October issue of Headache.
The 6-point value and the 1-2 category improvement values in item-specific scores, they suggested, could be used as a benchmark to help other clinicians and researchers detect meaningful change in individual patients with chronic migraine. Although the user guide for HIT-6 highlights a 5-point change in the total score as clinically meaningful, the authors of the guide do not provide evidence for why the 5-point value signifies clinically meaningful change, they said.
Determining thresholds of clinically meaningful change
In their study, Dr. Houts and colleagues used distribution-based methods to gauge responder values for the HIT-6 total score, while item-specific HIT-6 analyses were measured with Patients’ Global Impression of Change (PGIC), reduction in migraine frequency through monthly migraine days (MMDs), and EuroQol 5 dimensions 5 levels visual analog scale (EQ-5D-5L VAS). The researchers also used HIT-6 values from a literature review and from analyses in PROMISE-2 to calculate “a final chronic migraine-specific responder definition value” between baseline and 12 weeks. Participants in the PROMISE-2 study were mostly women (88.2%) and white (91.0%) with a mean age of 40.5 years.
The literature search revealed responder thresholds for the HIT-6 total score in a range between a decrease of 3 points and 8 points. Within PROMISE-2, the HIT-6 total score responder threshold was found to be between –2.6 and –2.2, which the researchers rounded down to a decrease of 3 points. When taking both sets of responder thresholds into account, the researchers calculated the median responder value as –5.5, which was rounded down to a decrease in 6 points in the HIT-6 total score. “[The estimate] appears most appropriate for discriminating between individuals with chronic migraine who have experienced meaningful change over time and those who have not,” Dr. Houts and colleagues said.
For item-specific HIT-6 scores, the mean score changes were –1 points for categories involving severe pain, limiting activities, lying down, and –2 points for categories involving feeling tired, being fed up or irritated, and limiting concentration.
“Taken together, the current chronic migraine-specific results are consistent with values derived from general headache/migraine samples and suggest that a decrease of 6 points or more on the HIT-6 total score would be considered meaningful to chronic migraine patients,” Dr. Houts and colleagues said. “This would translate to approximately a 4-category change on a single item, change on 2 items of approximately 2 and 3 categories, or a 1-category change on 3 or 4 of the 6 items, depending on the initial category.”
The researchers cautioned that the values outlined in the study “should not be used to determine clinically meaningful difference between treatment groups” and that “future work, similar to that reported here, will identify a chronic migraine-specific clinically meaningful difference between treatment groups value.”
A better measure of chronic migraine?
In an interview, J. D. Bartleson Jr., MD, a retired neurologist with the Mayo Clinic in Rochester, Minn., questioned why HIT-6 criteria was used in the initial PROMISE-2 study. “There is not a lot of difference between the significant and insignificant categories. Chronic migraine may be better measured with pain severity and number of headache days per month,” he said.
,“It may be appropriate to use just 1 or 2 symptoms for evaluating a given patient’s headache burden,” in terms of clinical application of the study for neurologists, Dr. Bartleson said. He emphasized that more research is needed.
This study was funded by H. Lundbeck A/S, which also provided funding of medical writing and editorial support for the manuscript. Three authors report being employees of Vector Psychometric Group at the time of the study, and the company received funding from H. Lundbeck A/S for their time conducting study-related research. Three other authors report relationships with pharmaceutical companies, medical societies, government agencies, and industry related to the study in the form of consultancies, advisory board memberships, honoraria, research support, stock or stock options, and employment. Dr. Bartleson reports no relevant conflicts of interest.
, recent research suggests.
Using data from the phase 3 PROMISE-2 study, which evaluated intravenous eptinezumab in doses of 100 mg or 300 mg, or placebo every 12 weeks in 1,072 participants for the prevention of chronic migraine, Carrie R. Houts, PhD, director of psychometrics at the Vector Psychometric Group, in Chapel Hill, N.C., and colleagues determined that their finding of 6-point improvement of HIT-6 total score was consistent with other studies. However, they pointed out that little research has been done in evaluating how item-specific scores of HIT-6 impact individuals with chronic migraine. HIT-6 item scores examine whether individuals with headaches experience severe pain, limit their daily activities, have a desire to lie down, feel too tired to do daily activities, felt “fed up or irritated” because of headaches, and feel their headaches limit concentration on work or daily activities.
“The item-specific responder definitions give clinicians and researchers the ability to evaluate and track the impact of headache on specific item-level areas of patients’ lives. These responder definitions provide practical and easily interpreted results that can be used to evaluate treatment benefits over time and to improve clinician-patients communication focus on improvements in key aspects of functioning in individuals with chronic migraine,” Dr. Houts and colleagues wrote in their study, published in the October issue of Headache.
The 6-point value and the 1-2 category improvement values in item-specific scores, they suggested, could be used as a benchmark to help other clinicians and researchers detect meaningful change in individual patients with chronic migraine. Although the user guide for HIT-6 highlights a 5-point change in the total score as clinically meaningful, the authors of the guide do not provide evidence for why the 5-point value signifies clinically meaningful change, they said.
Determining thresholds of clinically meaningful change
In their study, Dr. Houts and colleagues used distribution-based methods to gauge responder values for the HIT-6 total score, while item-specific HIT-6 analyses were measured with Patients’ Global Impression of Change (PGIC), reduction in migraine frequency through monthly migraine days (MMDs), and EuroQol 5 dimensions 5 levels visual analog scale (EQ-5D-5L VAS). The researchers also used HIT-6 values from a literature review and from analyses in PROMISE-2 to calculate “a final chronic migraine-specific responder definition value” between baseline and 12 weeks. Participants in the PROMISE-2 study were mostly women (88.2%) and white (91.0%) with a mean age of 40.5 years.
The literature search revealed responder thresholds for the HIT-6 total score in a range between a decrease of 3 points and 8 points. Within PROMISE-2, the HIT-6 total score responder threshold was found to be between –2.6 and –2.2, which the researchers rounded down to a decrease of 3 points. When taking both sets of responder thresholds into account, the researchers calculated the median responder value as –5.5, which was rounded down to a decrease in 6 points in the HIT-6 total score. “[The estimate] appears most appropriate for discriminating between individuals with chronic migraine who have experienced meaningful change over time and those who have not,” Dr. Houts and colleagues said.
For item-specific HIT-6 scores, the mean score changes were –1 points for categories involving severe pain, limiting activities, lying down, and –2 points for categories involving feeling tired, being fed up or irritated, and limiting concentration.
“Taken together, the current chronic migraine-specific results are consistent with values derived from general headache/migraine samples and suggest that a decrease of 6 points or more on the HIT-6 total score would be considered meaningful to chronic migraine patients,” Dr. Houts and colleagues said. “This would translate to approximately a 4-category change on a single item, change on 2 items of approximately 2 and 3 categories, or a 1-category change on 3 or 4 of the 6 items, depending on the initial category.”
The researchers cautioned that the values outlined in the study “should not be used to determine clinically meaningful difference between treatment groups” and that “future work, similar to that reported here, will identify a chronic migraine-specific clinically meaningful difference between treatment groups value.”
A better measure of chronic migraine?
In an interview, J. D. Bartleson Jr., MD, a retired neurologist with the Mayo Clinic in Rochester, Minn., questioned why HIT-6 criteria was used in the initial PROMISE-2 study. “There is not a lot of difference between the significant and insignificant categories. Chronic migraine may be better measured with pain severity and number of headache days per month,” he said.
,“It may be appropriate to use just 1 or 2 symptoms for evaluating a given patient’s headache burden,” in terms of clinical application of the study for neurologists, Dr. Bartleson said. He emphasized that more research is needed.
This study was funded by H. Lundbeck A/S, which also provided funding of medical writing and editorial support for the manuscript. Three authors report being employees of Vector Psychometric Group at the time of the study, and the company received funding from H. Lundbeck A/S for their time conducting study-related research. Three other authors report relationships with pharmaceutical companies, medical societies, government agencies, and industry related to the study in the form of consultancies, advisory board memberships, honoraria, research support, stock or stock options, and employment. Dr. Bartleson reports no relevant conflicts of interest.
, recent research suggests.
Using data from the phase 3 PROMISE-2 study, which evaluated intravenous eptinezumab in doses of 100 mg or 300 mg, or placebo every 12 weeks in 1,072 participants for the prevention of chronic migraine, Carrie R. Houts, PhD, director of psychometrics at the Vector Psychometric Group, in Chapel Hill, N.C., and colleagues determined that their finding of 6-point improvement of HIT-6 total score was consistent with other studies. However, they pointed out that little research has been done in evaluating how item-specific scores of HIT-6 impact individuals with chronic migraine. HIT-6 item scores examine whether individuals with headaches experience severe pain, limit their daily activities, have a desire to lie down, feel too tired to do daily activities, felt “fed up or irritated” because of headaches, and feel their headaches limit concentration on work or daily activities.
“The item-specific responder definitions give clinicians and researchers the ability to evaluate and track the impact of headache on specific item-level areas of patients’ lives. These responder definitions provide practical and easily interpreted results that can be used to evaluate treatment benefits over time and to improve clinician-patients communication focus on improvements in key aspects of functioning in individuals with chronic migraine,” Dr. Houts and colleagues wrote in their study, published in the October issue of Headache.
The 6-point value and the 1-2 category improvement values in item-specific scores, they suggested, could be used as a benchmark to help other clinicians and researchers detect meaningful change in individual patients with chronic migraine. Although the user guide for HIT-6 highlights a 5-point change in the total score as clinically meaningful, the authors of the guide do not provide evidence for why the 5-point value signifies clinically meaningful change, they said.
Determining thresholds of clinically meaningful change
In their study, Dr. Houts and colleagues used distribution-based methods to gauge responder values for the HIT-6 total score, while item-specific HIT-6 analyses were measured with Patients’ Global Impression of Change (PGIC), reduction in migraine frequency through monthly migraine days (MMDs), and EuroQol 5 dimensions 5 levels visual analog scale (EQ-5D-5L VAS). The researchers also used HIT-6 values from a literature review and from analyses in PROMISE-2 to calculate “a final chronic migraine-specific responder definition value” between baseline and 12 weeks. Participants in the PROMISE-2 study were mostly women (88.2%) and white (91.0%) with a mean age of 40.5 years.
The literature search revealed responder thresholds for the HIT-6 total score in a range between a decrease of 3 points and 8 points. Within PROMISE-2, the HIT-6 total score responder threshold was found to be between –2.6 and –2.2, which the researchers rounded down to a decrease of 3 points. When taking both sets of responder thresholds into account, the researchers calculated the median responder value as –5.5, which was rounded down to a decrease in 6 points in the HIT-6 total score. “[The estimate] appears most appropriate for discriminating between individuals with chronic migraine who have experienced meaningful change over time and those who have not,” Dr. Houts and colleagues said.
For item-specific HIT-6 scores, the mean score changes were –1 points for categories involving severe pain, limiting activities, lying down, and –2 points for categories involving feeling tired, being fed up or irritated, and limiting concentration.
“Taken together, the current chronic migraine-specific results are consistent with values derived from general headache/migraine samples and suggest that a decrease of 6 points or more on the HIT-6 total score would be considered meaningful to chronic migraine patients,” Dr. Houts and colleagues said. “This would translate to approximately a 4-category change on a single item, change on 2 items of approximately 2 and 3 categories, or a 1-category change on 3 or 4 of the 6 items, depending on the initial category.”
The researchers cautioned that the values outlined in the study “should not be used to determine clinically meaningful difference between treatment groups” and that “future work, similar to that reported here, will identify a chronic migraine-specific clinically meaningful difference between treatment groups value.”
A better measure of chronic migraine?
In an interview, J. D. Bartleson Jr., MD, a retired neurologist with the Mayo Clinic in Rochester, Minn., questioned why HIT-6 criteria was used in the initial PROMISE-2 study. “There is not a lot of difference between the significant and insignificant categories. Chronic migraine may be better measured with pain severity and number of headache days per month,” he said.
,“It may be appropriate to use just 1 or 2 symptoms for evaluating a given patient’s headache burden,” in terms of clinical application of the study for neurologists, Dr. Bartleson said. He emphasized that more research is needed.
This study was funded by H. Lundbeck A/S, which also provided funding of medical writing and editorial support for the manuscript. Three authors report being employees of Vector Psychometric Group at the time of the study, and the company received funding from H. Lundbeck A/S for their time conducting study-related research. Three other authors report relationships with pharmaceutical companies, medical societies, government agencies, and industry related to the study in the form of consultancies, advisory board memberships, honoraria, research support, stock or stock options, and employment. Dr. Bartleson reports no relevant conflicts of interest.
FROM HEADACHE
Endometriosis, surgical approach impact risk of bowel injury in hysterectomy
Hysterectomies performed using an abdominal surgical approach or in women with endometriosis are more likely to carry an increased risk of bowel injury, according to recent results published in Obstetrics & Gynecology.
Cici R. Zhu, MD, of the department of obstetrics and gynecology at the University of Ottawa, and colleagues retrospectively studied the incidence of bowel injury in women participating in the American College of Surgeons National Surgical Quality Improvement Program who underwent hysterectomy for a benign surgical indication between 2012 and 2016.
“Although the absolute incidence is low, bowel injuries are among the most devastating complications of hysterectomy, as they can lead to a wide range of complications, including peritonitis, abscess formation, enterocutaneous fistula, sepsis, and even death,” Dr. Zhu and colleagues wrote. “Secondary bowel surgeries are often required, and associated ileostomies and colostomies can be distressing to patients. This not only severely affects quality of life, but the resultant readmissions, reoperations, and prolonged hospitalizations can impose a substantial economic toll on the health care system.”
Overall, 155,557 women were included in the study. The cohort consisted of women who were a mean age of 48 years and had a mean body mass index (BMI) of 31 kg/m2. The researchers evaluated whether baseline characteristics, clinical, and surgical variables impacted the incidence of bowel injury. They analyzed data of participant age, race (White vs. non-White), BMI, comorbid conditions (smoking, diabetes, chronic obstructive pulmonary disease, hypertension, and bleeding disorder), American Society of Anesthesiologists (ASA) classification, surgical approach (abdominal, laparoscopic, or vaginal), hysterectomy type (total or subtotal), lysis of adhesions, operation time, and admission type. Indication for hysterectomy was also evaluated, which included uterine leiomyoma (32.9%), menstrual disorders (22.0%), genital prolapse (13.1%), endometriosis (6.8%) and pelvic pain (3.8%).
Endometriosis, abdominal approach raise risk
There were 610 cases of bowel injury observed in the study, for an overall injury rate of 0.39%. A majority of the repairs were done during surgery (82.3%), with the remainder performed within 30 days of hysterectomy. Women with endometriosis had the most frequent incidence of bowel injury (0.59%), but it also occurred in women with uterine leiomyomas (0.47%), pain (0.24%), menstrual disorders (0.20%), genital prolapse (0.18%) and other indications (0.56%).
Dr. Zhu and colleagues found risk of bowel injury was higher among women 55 years and older, compared with women aged younger than 40 years (odds ratio, 1.66; 95% confidence interval, 1.28-2.15); in non-White women, compared with White women (OR, 1.92; 95% CI, 1.62-2.28); and in women with class 3 obesity, compared with women at a normal BMI (OR, 1.81; 95 CI, 1.40-2.34). Other risk factors for bowel injury included hypertension (OR, 1.39; 95% CI, 1.17-1.64) and ASA III, IV, and V classification, compared with ASA I classification (OR, 1.92; 95% CI, 1.43-2.58).
Researchers noted there was a statistically significant difference in rates of bowel injury between hysterectomy indications (P < .001). When compared with endometriosis, there were lower odds of bowel injury among women with uterine leiomyomas (adjusted odds ratio, 0.44; 95% confidence interval, 0.33-0.59), genital prolapse (aOR, 0.41; 95% CI, 0.25-0.67), and menstrual disorder (aOR, 0.33; 95% CI, 0.23-0.48).
Surgical factors also impacted the risk for bowel injury. In hysterectomies where the abdominal approach was used, there was an over-tenfold risk of bowel injury, compared with when a vaginal approach was used (OR, 10.80; 95% CI, 7.31-15.95). Lysis of lesions carried an increased risk of bowel injury (OR, 3.11; 95% CI, 2.20-4.40), and a subtotal hysterectomy increased the risk of bowel injury, compared with when a total hysterectomy was performed (OR, 1.76; 95% CI, 1.42-2.18).
The researchers acknowledged the lack of detailed clinical information on surgical indications, severity of bowel injury, and training of the surgeons and surgical team, and potential for missing information may limit the application of the study findings.
Findings must be cautiously interpreted
Kate Stampler, DO, assistant program director of minimally invasive gynecologic robotic surgery at Einstein Healthcare Network in Philadelphia, said in an interview that the study by Zhu et al. is a good reminder of the patient and surgical risk factors that can occur that affect outcomes of hysterectomy.
“In my clinical practice, I have not seen a significant difference in route of hysterectomy and bowel injury, however, this must be interpreted carefully in the context of an infrequent complication and as an MIS [minimally invasive surgery]-trained surgeon performing various complex cases,” she said. Other reports in the literature have not identified a difference in the rate of bowel injury based on surgical approach, but the study by Zhu et al. is “unique to the literature in its large sample size,” she explained.
“I would encourage less experienced surgeons to operate with a higher-volume assistant surgeon if the end result means being able to perform an MIS approach, or appropriately offer referral if feasible to another surgeon for best practices. A thorough informed consent of the available route of hysterectomy is integral to good surgical care and allows for shared decision making for the patient,” Dr. Stampler said. “Additionally, participation in a large quality reporting system such as ACS National Surgical Quality Improvement Program database should be considered broadly and we should strive for overall high-value care.”
Regarding endometriosis being a risk factor for bowel injury during hysterectomy, Dr. Stampler noted that severe endometriosis poses a significant challenge for gynecologic surgeons. “Loss of anatomic planes due to dense adhesions and fibrosis, in addition to deep infiltrating lesions, can add significant time, complexity, and risk to the procedure. This can be compounded in a scenario with less experienced surgeons and unplanned disease at the time of surgery.”
Dr. Stampler also applauded the paper for highlighting the differences in White and non-White patient outcomes for hysterectomy, and emphasized that it is not new information. “Their call to continue to address the social determinants of health in an effort to minimize risk and maximize safety for our patients of color is of critical importance now more than ever. While the hypothesis for this study was not meant to address this challenge specifically, the data should serve as a striking reminder that while several factors may be playing a role in surgical complications, ongoing systemic racism is a component that needs dedicated time and attention.”
Dr. Zhu and three coauthors reported no relevant financial disclosures. One coauthor received support from the University of Ottawa Clinical Research Chair in Reproductive Population Health and Health Services, the Canadian Institutes for Health Research, and Physicians’ Services Incorporated Foundation to conduct this research. Two other coauthors reported financial relationships with various pharmaceutical and medical technology companies. Dr. Stampler reported no relevant conflicts of interest.
SOURCE: Zhu CR et al. Obstet Gynecol. 2020 Oct. doi: 10.1097/AOG.0000000000004007.
Hysterectomies performed using an abdominal surgical approach or in women with endometriosis are more likely to carry an increased risk of bowel injury, according to recent results published in Obstetrics & Gynecology.
Cici R. Zhu, MD, of the department of obstetrics and gynecology at the University of Ottawa, and colleagues retrospectively studied the incidence of bowel injury in women participating in the American College of Surgeons National Surgical Quality Improvement Program who underwent hysterectomy for a benign surgical indication between 2012 and 2016.
“Although the absolute incidence is low, bowel injuries are among the most devastating complications of hysterectomy, as they can lead to a wide range of complications, including peritonitis, abscess formation, enterocutaneous fistula, sepsis, and even death,” Dr. Zhu and colleagues wrote. “Secondary bowel surgeries are often required, and associated ileostomies and colostomies can be distressing to patients. This not only severely affects quality of life, but the resultant readmissions, reoperations, and prolonged hospitalizations can impose a substantial economic toll on the health care system.”
Overall, 155,557 women were included in the study. The cohort consisted of women who were a mean age of 48 years and had a mean body mass index (BMI) of 31 kg/m2. The researchers evaluated whether baseline characteristics, clinical, and surgical variables impacted the incidence of bowel injury. They analyzed data of participant age, race (White vs. non-White), BMI, comorbid conditions (smoking, diabetes, chronic obstructive pulmonary disease, hypertension, and bleeding disorder), American Society of Anesthesiologists (ASA) classification, surgical approach (abdominal, laparoscopic, or vaginal), hysterectomy type (total or subtotal), lysis of adhesions, operation time, and admission type. Indication for hysterectomy was also evaluated, which included uterine leiomyoma (32.9%), menstrual disorders (22.0%), genital prolapse (13.1%), endometriosis (6.8%) and pelvic pain (3.8%).
Endometriosis, abdominal approach raise risk
There were 610 cases of bowel injury observed in the study, for an overall injury rate of 0.39%. A majority of the repairs were done during surgery (82.3%), with the remainder performed within 30 days of hysterectomy. Women with endometriosis had the most frequent incidence of bowel injury (0.59%), but it also occurred in women with uterine leiomyomas (0.47%), pain (0.24%), menstrual disorders (0.20%), genital prolapse (0.18%) and other indications (0.56%).
Dr. Zhu and colleagues found risk of bowel injury was higher among women 55 years and older, compared with women aged younger than 40 years (odds ratio, 1.66; 95% confidence interval, 1.28-2.15); in non-White women, compared with White women (OR, 1.92; 95% CI, 1.62-2.28); and in women with class 3 obesity, compared with women at a normal BMI (OR, 1.81; 95 CI, 1.40-2.34). Other risk factors for bowel injury included hypertension (OR, 1.39; 95% CI, 1.17-1.64) and ASA III, IV, and V classification, compared with ASA I classification (OR, 1.92; 95% CI, 1.43-2.58).
Researchers noted there was a statistically significant difference in rates of bowel injury between hysterectomy indications (P < .001). When compared with endometriosis, there were lower odds of bowel injury among women with uterine leiomyomas (adjusted odds ratio, 0.44; 95% confidence interval, 0.33-0.59), genital prolapse (aOR, 0.41; 95% CI, 0.25-0.67), and menstrual disorder (aOR, 0.33; 95% CI, 0.23-0.48).
Surgical factors also impacted the risk for bowel injury. In hysterectomies where the abdominal approach was used, there was an over-tenfold risk of bowel injury, compared with when a vaginal approach was used (OR, 10.80; 95% CI, 7.31-15.95). Lysis of lesions carried an increased risk of bowel injury (OR, 3.11; 95% CI, 2.20-4.40), and a subtotal hysterectomy increased the risk of bowel injury, compared with when a total hysterectomy was performed (OR, 1.76; 95% CI, 1.42-2.18).
The researchers acknowledged the lack of detailed clinical information on surgical indications, severity of bowel injury, and training of the surgeons and surgical team, and potential for missing information may limit the application of the study findings.
Findings must be cautiously interpreted
Kate Stampler, DO, assistant program director of minimally invasive gynecologic robotic surgery at Einstein Healthcare Network in Philadelphia, said in an interview that the study by Zhu et al. is a good reminder of the patient and surgical risk factors that can occur that affect outcomes of hysterectomy.
“In my clinical practice, I have not seen a significant difference in route of hysterectomy and bowel injury, however, this must be interpreted carefully in the context of an infrequent complication and as an MIS [minimally invasive surgery]-trained surgeon performing various complex cases,” she said. Other reports in the literature have not identified a difference in the rate of bowel injury based on surgical approach, but the study by Zhu et al. is “unique to the literature in its large sample size,” she explained.
“I would encourage less experienced surgeons to operate with a higher-volume assistant surgeon if the end result means being able to perform an MIS approach, or appropriately offer referral if feasible to another surgeon for best practices. A thorough informed consent of the available route of hysterectomy is integral to good surgical care and allows for shared decision making for the patient,” Dr. Stampler said. “Additionally, participation in a large quality reporting system such as ACS National Surgical Quality Improvement Program database should be considered broadly and we should strive for overall high-value care.”
Regarding endometriosis being a risk factor for bowel injury during hysterectomy, Dr. Stampler noted that severe endometriosis poses a significant challenge for gynecologic surgeons. “Loss of anatomic planes due to dense adhesions and fibrosis, in addition to deep infiltrating lesions, can add significant time, complexity, and risk to the procedure. This can be compounded in a scenario with less experienced surgeons and unplanned disease at the time of surgery.”
Dr. Stampler also applauded the paper for highlighting the differences in White and non-White patient outcomes for hysterectomy, and emphasized that it is not new information. “Their call to continue to address the social determinants of health in an effort to minimize risk and maximize safety for our patients of color is of critical importance now more than ever. While the hypothesis for this study was not meant to address this challenge specifically, the data should serve as a striking reminder that while several factors may be playing a role in surgical complications, ongoing systemic racism is a component that needs dedicated time and attention.”
Dr. Zhu and three coauthors reported no relevant financial disclosures. One coauthor received support from the University of Ottawa Clinical Research Chair in Reproductive Population Health and Health Services, the Canadian Institutes for Health Research, and Physicians’ Services Incorporated Foundation to conduct this research. Two other coauthors reported financial relationships with various pharmaceutical and medical technology companies. Dr. Stampler reported no relevant conflicts of interest.
SOURCE: Zhu CR et al. Obstet Gynecol. 2020 Oct. doi: 10.1097/AOG.0000000000004007.
Hysterectomies performed using an abdominal surgical approach or in women with endometriosis are more likely to carry an increased risk of bowel injury, according to recent results published in Obstetrics & Gynecology.
Cici R. Zhu, MD, of the department of obstetrics and gynecology at the University of Ottawa, and colleagues retrospectively studied the incidence of bowel injury in women participating in the American College of Surgeons National Surgical Quality Improvement Program who underwent hysterectomy for a benign surgical indication between 2012 and 2016.
“Although the absolute incidence is low, bowel injuries are among the most devastating complications of hysterectomy, as they can lead to a wide range of complications, including peritonitis, abscess formation, enterocutaneous fistula, sepsis, and even death,” Dr. Zhu and colleagues wrote. “Secondary bowel surgeries are often required, and associated ileostomies and colostomies can be distressing to patients. This not only severely affects quality of life, but the resultant readmissions, reoperations, and prolonged hospitalizations can impose a substantial economic toll on the health care system.”
Overall, 155,557 women were included in the study. The cohort consisted of women who were a mean age of 48 years and had a mean body mass index (BMI) of 31 kg/m2. The researchers evaluated whether baseline characteristics, clinical, and surgical variables impacted the incidence of bowel injury. They analyzed data of participant age, race (White vs. non-White), BMI, comorbid conditions (smoking, diabetes, chronic obstructive pulmonary disease, hypertension, and bleeding disorder), American Society of Anesthesiologists (ASA) classification, surgical approach (abdominal, laparoscopic, or vaginal), hysterectomy type (total or subtotal), lysis of adhesions, operation time, and admission type. Indication for hysterectomy was also evaluated, which included uterine leiomyoma (32.9%), menstrual disorders (22.0%), genital prolapse (13.1%), endometriosis (6.8%) and pelvic pain (3.8%).
Endometriosis, abdominal approach raise risk
There were 610 cases of bowel injury observed in the study, for an overall injury rate of 0.39%. A majority of the repairs were done during surgery (82.3%), with the remainder performed within 30 days of hysterectomy. Women with endometriosis had the most frequent incidence of bowel injury (0.59%), but it also occurred in women with uterine leiomyomas (0.47%), pain (0.24%), menstrual disorders (0.20%), genital prolapse (0.18%) and other indications (0.56%).
Dr. Zhu and colleagues found risk of bowel injury was higher among women 55 years and older, compared with women aged younger than 40 years (odds ratio, 1.66; 95% confidence interval, 1.28-2.15); in non-White women, compared with White women (OR, 1.92; 95% CI, 1.62-2.28); and in women with class 3 obesity, compared with women at a normal BMI (OR, 1.81; 95 CI, 1.40-2.34). Other risk factors for bowel injury included hypertension (OR, 1.39; 95% CI, 1.17-1.64) and ASA III, IV, and V classification, compared with ASA I classification (OR, 1.92; 95% CI, 1.43-2.58).
Researchers noted there was a statistically significant difference in rates of bowel injury between hysterectomy indications (P < .001). When compared with endometriosis, there were lower odds of bowel injury among women with uterine leiomyomas (adjusted odds ratio, 0.44; 95% confidence interval, 0.33-0.59), genital prolapse (aOR, 0.41; 95% CI, 0.25-0.67), and menstrual disorder (aOR, 0.33; 95% CI, 0.23-0.48).
Surgical factors also impacted the risk for bowel injury. In hysterectomies where the abdominal approach was used, there was an over-tenfold risk of bowel injury, compared with when a vaginal approach was used (OR, 10.80; 95% CI, 7.31-15.95). Lysis of lesions carried an increased risk of bowel injury (OR, 3.11; 95% CI, 2.20-4.40), and a subtotal hysterectomy increased the risk of bowel injury, compared with when a total hysterectomy was performed (OR, 1.76; 95% CI, 1.42-2.18).
The researchers acknowledged the lack of detailed clinical information on surgical indications, severity of bowel injury, and training of the surgeons and surgical team, and potential for missing information may limit the application of the study findings.
Findings must be cautiously interpreted
Kate Stampler, DO, assistant program director of minimally invasive gynecologic robotic surgery at Einstein Healthcare Network in Philadelphia, said in an interview that the study by Zhu et al. is a good reminder of the patient and surgical risk factors that can occur that affect outcomes of hysterectomy.
“In my clinical practice, I have not seen a significant difference in route of hysterectomy and bowel injury, however, this must be interpreted carefully in the context of an infrequent complication and as an MIS [minimally invasive surgery]-trained surgeon performing various complex cases,” she said. Other reports in the literature have not identified a difference in the rate of bowel injury based on surgical approach, but the study by Zhu et al. is “unique to the literature in its large sample size,” she explained.
“I would encourage less experienced surgeons to operate with a higher-volume assistant surgeon if the end result means being able to perform an MIS approach, or appropriately offer referral if feasible to another surgeon for best practices. A thorough informed consent of the available route of hysterectomy is integral to good surgical care and allows for shared decision making for the patient,” Dr. Stampler said. “Additionally, participation in a large quality reporting system such as ACS National Surgical Quality Improvement Program database should be considered broadly and we should strive for overall high-value care.”
Regarding endometriosis being a risk factor for bowel injury during hysterectomy, Dr. Stampler noted that severe endometriosis poses a significant challenge for gynecologic surgeons. “Loss of anatomic planes due to dense adhesions and fibrosis, in addition to deep infiltrating lesions, can add significant time, complexity, and risk to the procedure. This can be compounded in a scenario with less experienced surgeons and unplanned disease at the time of surgery.”
Dr. Stampler also applauded the paper for highlighting the differences in White and non-White patient outcomes for hysterectomy, and emphasized that it is not new information. “Their call to continue to address the social determinants of health in an effort to minimize risk and maximize safety for our patients of color is of critical importance now more than ever. While the hypothesis for this study was not meant to address this challenge specifically, the data should serve as a striking reminder that while several factors may be playing a role in surgical complications, ongoing systemic racism is a component that needs dedicated time and attention.”
Dr. Zhu and three coauthors reported no relevant financial disclosures. One coauthor received support from the University of Ottawa Clinical Research Chair in Reproductive Population Health and Health Services, the Canadian Institutes for Health Research, and Physicians’ Services Incorporated Foundation to conduct this research. Two other coauthors reported financial relationships with various pharmaceutical and medical technology companies. Dr. Stampler reported no relevant conflicts of interest.
SOURCE: Zhu CR et al. Obstet Gynecol. 2020 Oct. doi: 10.1097/AOG.0000000000004007.
FROM OBSTETRICS & GYNECOLOGY
Enhanced recovery program improves outcomes after cesarean delivery
according to recent research published in Obstetrics & Gynecology.
Luciana Mullman, MPH, of Saint Barnabas Medical Center in Livingston, N.J., and colleagues used a pre-post study design to evaluate the effectiveness of ERAS at a tertiary care institution after implementing the program for patients undergoing scheduled or emergent cesarean delivery between December 2018 and August 2019. The researchers compared the rates of opioid use, length of stay, and costs of care for patients undergoing cesarean section after ERAS was implemented with those outcomes for cesarean deliveries at the center prior to ERAS between January 2018 and December 2018.
The ERAS program
ERAS was described in the study as incorporating a preoperative strategy, intraoperative management and postoperative care for cesarean delivery. The preoperative strategy consisted of a patient guidebook and a personal meeting for patient education on what to expect for preoperative and postoperative experiences as well as instructions leading up to the surgery.
For intraoperative management, intravenous opioids were minimized and replaced with neuraxial opioids when appropriate. The patient’s body temperature was monitored and controlled during the intraoperative pathway, and fluid balance was maintained. To prevent postoperative nausea and vomiting, IV ondansetron at a dose of 4 mg was started at the beginning of the cesarean delivery. When the cesarean delivery was complete, an anesthesiologist administered transversus abdominis plane blocks with 0.3% ropivacaine 30 mL on each side before the patient moved to the recovery area.
Postoperatively, the patient’s catheter was removed in the recovery room, and then transferred to postpartum floors if appropriate based on patient status. Patients began resuming a clear liquid diet 1 hour after cesarean delivery and a regular diet 6 hours after delivery. At 6 hours after surgery, the patient was out of bed and moving; walks around the nursing unit were scheduled three times per day at minimum. For pain, patients were given a 1,000-mg acetaminophen tablet every 8 hours, a 600-mg ibuprofen tablet every 6 hours, and dextromethorphan 30 mg/mL every 8 hours, with oral oxycodone 5 mg administered after physician evaluation for breakthrough pain.
Overall, there were 3,679 cesarean deliveries in the study, which included 2,171 deliveries prior to ERAS implementation and 1,508 cesarean deliveries after implementation. Patients with a scheduled cesarean delivery prior to ERAS implementation received no consistent educational program for anticipating cesarean delivery. After implementation, those patients with scheduled cesarean delivery received the full preoperative, intraoperative, and postoperative pathway, while emergent cesarean cases included the intraoperative management and postoperative care, but did not contain the preoperative component.
Improved outcomes after ERAS
The researchers found a significant decrease in the use of opioids after implementing ERAS at the center, with 24% of patients receiving opioids after ERAS, compared with 84% of patients prior to ERAS (odds ratio, 16.8; 95% confidence interval, 14.3-19.9; P < .001). These reductions in opioid use from the pre- and postimplementation periods were similar for patients with scheduled cesarean deliveries (85% vs. 27%; OR, 14.9; 95% CI, 12.2-18.3; P < .001) and emergent cesarean deliveries (83% vs. 19%; OR, 21.4; 95% CI, 16.1-28.7; P < .001).
There was also a significant reduction in total morphine milligram equivalents (MME) for patients who received opioids after ERAS (median, 15.0 MME), compared with before (median, 56.5 MME) implementing ERAS (mean relative change, 0.32; 95% CI, 0.28-0.35; P < .001). These results also were significant among both scheduled (median 59.9 vs. 15.0 MME; mean relative change, 0.31; 95% CI, 0.27-0.36; P < .001) and emergent (median 56.5 vs. 15.0 MME; mean relative change, 0.95; 95% CI, 0.89-1.01; P < .001) cesarean deliveries.
The overall length of stay after cesarean delivery significantly decreased after ERAS from an average of 3.2 days to 2.7 days (mean relative change, 0.82, 95% CI, 0.80-0.83; P < .001), and was significant in both scheduled (3.2 vs. 2.7 days; mean relative change, 0.83; 95% CI, 0.81-0.85; P < .001) and emergent (3.1 vs. 2.5 days; mean relative change, 0.80; 95% CI, 0.77-0.82; P < .001) groups. While the number of patients discharged within 2 days increased from 9% to 49% after ERAS implementation, there was no significant difference overall or in either group regarding 30-day readmission. The researchers also noted the median direct costs of cesarean delivery decreased by $349 per case after starting ERAS (mean relative change, 0.93; 95% CI, 0.91-0.95).
ERAS implementation lagging in obstetrics
In an interview, Iris Krishna, MD, MPH, a maternal-fetal medicine specialist at Emory University, Atlanta, said the ERAS approach has been used successfully in other surgical specialties but has “lagged” in obstetrics. “To date, there has been less attention in improving perioperative outcomes for women undergoing cesarean delivery, the most common abdominal surgery for women.”
Dr. Krishna said this study shows ERAS can be used in obstetrics to improve outcomes after cesarean section without increasing readmission rates. “Overall, this study demonstrates that ERAS can be successfully implemented for cesarean delivery as it has been for a variety of surgical specialties. ERAS for cesarean delivery can improve the quality of patient care while reducing health care costs.”
Women in the postpartum and postoperative period could benefit from ERAS as they recover from surgery and adjust to becoming a new mother, Dr. Krishna noted. “The goal of ERAS is to help patients return to physiological functioning as quickly as possible. Improving postoperative recovery can help with mother-infant bonding and breastfeeding.
“Implementation of a standardized approach for cesarean delivery has the potential to reduce health disparities and the disproportionately high rates of maternal morbidity and mortality in the United States,” she added. “ERAS for cesarean delivery also has the potential to address the opioid epidemic amongst reproductive-age women by improving postcesarean pain management and reducing opioid prescribing.”
Dr. Krishna also explained that an ERAS program would be feasible to implement in most centers. “It will require a shift of some elements of care from the inpatient to outpatient setting, but theoretically feasible as pregnant women frequently undergo many clinic visits during their pregnancy course.
“Education on ERAS for cesarean delivery can be implemented into prenatal care visits. ERAS implementation will also require a multidisciplinary team approach that includes obstetrics, anesthesia, nursing, pharmacy, pediatrics – all key stakeholders that will need to ‘buy in’ or be willing to support the protocol to ensure its success. As in this study, it would be helpful for hospitals to have an ERAS coordinator to champion and ensure compliance of protocol.”
Dr. Miller reported that he has received payments from the Coventus Professional Liability Insurance: Risk Management Committee and the New Jersey Board of Medical Examiners. The other authors reported no relevant conflicts of interest. Dr. Krishna reported no relevant conflicts of interest.
SOURCE: Mullman L et al. Obstet Gynecol. 2020 Oct. doi: 10.1097/AOG.0000000000004023.
according to recent research published in Obstetrics & Gynecology.
Luciana Mullman, MPH, of Saint Barnabas Medical Center in Livingston, N.J., and colleagues used a pre-post study design to evaluate the effectiveness of ERAS at a tertiary care institution after implementing the program for patients undergoing scheduled or emergent cesarean delivery between December 2018 and August 2019. The researchers compared the rates of opioid use, length of stay, and costs of care for patients undergoing cesarean section after ERAS was implemented with those outcomes for cesarean deliveries at the center prior to ERAS between January 2018 and December 2018.
The ERAS program
ERAS was described in the study as incorporating a preoperative strategy, intraoperative management and postoperative care for cesarean delivery. The preoperative strategy consisted of a patient guidebook and a personal meeting for patient education on what to expect for preoperative and postoperative experiences as well as instructions leading up to the surgery.
For intraoperative management, intravenous opioids were minimized and replaced with neuraxial opioids when appropriate. The patient’s body temperature was monitored and controlled during the intraoperative pathway, and fluid balance was maintained. To prevent postoperative nausea and vomiting, IV ondansetron at a dose of 4 mg was started at the beginning of the cesarean delivery. When the cesarean delivery was complete, an anesthesiologist administered transversus abdominis plane blocks with 0.3% ropivacaine 30 mL on each side before the patient moved to the recovery area.
Postoperatively, the patient’s catheter was removed in the recovery room, and then transferred to postpartum floors if appropriate based on patient status. Patients began resuming a clear liquid diet 1 hour after cesarean delivery and a regular diet 6 hours after delivery. At 6 hours after surgery, the patient was out of bed and moving; walks around the nursing unit were scheduled three times per day at minimum. For pain, patients were given a 1,000-mg acetaminophen tablet every 8 hours, a 600-mg ibuprofen tablet every 6 hours, and dextromethorphan 30 mg/mL every 8 hours, with oral oxycodone 5 mg administered after physician evaluation for breakthrough pain.
Overall, there were 3,679 cesarean deliveries in the study, which included 2,171 deliveries prior to ERAS implementation and 1,508 cesarean deliveries after implementation. Patients with a scheduled cesarean delivery prior to ERAS implementation received no consistent educational program for anticipating cesarean delivery. After implementation, those patients with scheduled cesarean delivery received the full preoperative, intraoperative, and postoperative pathway, while emergent cesarean cases included the intraoperative management and postoperative care, but did not contain the preoperative component.
Improved outcomes after ERAS
The researchers found a significant decrease in the use of opioids after implementing ERAS at the center, with 24% of patients receiving opioids after ERAS, compared with 84% of patients prior to ERAS (odds ratio, 16.8; 95% confidence interval, 14.3-19.9; P < .001). These reductions in opioid use from the pre- and postimplementation periods were similar for patients with scheduled cesarean deliveries (85% vs. 27%; OR, 14.9; 95% CI, 12.2-18.3; P < .001) and emergent cesarean deliveries (83% vs. 19%; OR, 21.4; 95% CI, 16.1-28.7; P < .001).
There was also a significant reduction in total morphine milligram equivalents (MME) for patients who received opioids after ERAS (median, 15.0 MME), compared with before (median, 56.5 MME) implementing ERAS (mean relative change, 0.32; 95% CI, 0.28-0.35; P < .001). These results also were significant among both scheduled (median 59.9 vs. 15.0 MME; mean relative change, 0.31; 95% CI, 0.27-0.36; P < .001) and emergent (median 56.5 vs. 15.0 MME; mean relative change, 0.95; 95% CI, 0.89-1.01; P < .001) cesarean deliveries.
The overall length of stay after cesarean delivery significantly decreased after ERAS from an average of 3.2 days to 2.7 days (mean relative change, 0.82, 95% CI, 0.80-0.83; P < .001), and was significant in both scheduled (3.2 vs. 2.7 days; mean relative change, 0.83; 95% CI, 0.81-0.85; P < .001) and emergent (3.1 vs. 2.5 days; mean relative change, 0.80; 95% CI, 0.77-0.82; P < .001) groups. While the number of patients discharged within 2 days increased from 9% to 49% after ERAS implementation, there was no significant difference overall or in either group regarding 30-day readmission. The researchers also noted the median direct costs of cesarean delivery decreased by $349 per case after starting ERAS (mean relative change, 0.93; 95% CI, 0.91-0.95).
ERAS implementation lagging in obstetrics
In an interview, Iris Krishna, MD, MPH, a maternal-fetal medicine specialist at Emory University, Atlanta, said the ERAS approach has been used successfully in other surgical specialties but has “lagged” in obstetrics. “To date, there has been less attention in improving perioperative outcomes for women undergoing cesarean delivery, the most common abdominal surgery for women.”
Dr. Krishna said this study shows ERAS can be used in obstetrics to improve outcomes after cesarean section without increasing readmission rates. “Overall, this study demonstrates that ERAS can be successfully implemented for cesarean delivery as it has been for a variety of surgical specialties. ERAS for cesarean delivery can improve the quality of patient care while reducing health care costs.”
Women in the postpartum and postoperative period could benefit from ERAS as they recover from surgery and adjust to becoming a new mother, Dr. Krishna noted. “The goal of ERAS is to help patients return to physiological functioning as quickly as possible. Improving postoperative recovery can help with mother-infant bonding and breastfeeding.
“Implementation of a standardized approach for cesarean delivery has the potential to reduce health disparities and the disproportionately high rates of maternal morbidity and mortality in the United States,” she added. “ERAS for cesarean delivery also has the potential to address the opioid epidemic amongst reproductive-age women by improving postcesarean pain management and reducing opioid prescribing.”
Dr. Krishna also explained that an ERAS program would be feasible to implement in most centers. “It will require a shift of some elements of care from the inpatient to outpatient setting, but theoretically feasible as pregnant women frequently undergo many clinic visits during their pregnancy course.
“Education on ERAS for cesarean delivery can be implemented into prenatal care visits. ERAS implementation will also require a multidisciplinary team approach that includes obstetrics, anesthesia, nursing, pharmacy, pediatrics – all key stakeholders that will need to ‘buy in’ or be willing to support the protocol to ensure its success. As in this study, it would be helpful for hospitals to have an ERAS coordinator to champion and ensure compliance of protocol.”
Dr. Miller reported that he has received payments from the Coventus Professional Liability Insurance: Risk Management Committee and the New Jersey Board of Medical Examiners. The other authors reported no relevant conflicts of interest. Dr. Krishna reported no relevant conflicts of interest.
SOURCE: Mullman L et al. Obstet Gynecol. 2020 Oct. doi: 10.1097/AOG.0000000000004023.
according to recent research published in Obstetrics & Gynecology.
Luciana Mullman, MPH, of Saint Barnabas Medical Center in Livingston, N.J., and colleagues used a pre-post study design to evaluate the effectiveness of ERAS at a tertiary care institution after implementing the program for patients undergoing scheduled or emergent cesarean delivery between December 2018 and August 2019. The researchers compared the rates of opioid use, length of stay, and costs of care for patients undergoing cesarean section after ERAS was implemented with those outcomes for cesarean deliveries at the center prior to ERAS between January 2018 and December 2018.
The ERAS program
ERAS was described in the study as incorporating a preoperative strategy, intraoperative management and postoperative care for cesarean delivery. The preoperative strategy consisted of a patient guidebook and a personal meeting for patient education on what to expect for preoperative and postoperative experiences as well as instructions leading up to the surgery.
For intraoperative management, intravenous opioids were minimized and replaced with neuraxial opioids when appropriate. The patient’s body temperature was monitored and controlled during the intraoperative pathway, and fluid balance was maintained. To prevent postoperative nausea and vomiting, IV ondansetron at a dose of 4 mg was started at the beginning of the cesarean delivery. When the cesarean delivery was complete, an anesthesiologist administered transversus abdominis plane blocks with 0.3% ropivacaine 30 mL on each side before the patient moved to the recovery area.
Postoperatively, the patient’s catheter was removed in the recovery room, and then transferred to postpartum floors if appropriate based on patient status. Patients began resuming a clear liquid diet 1 hour after cesarean delivery and a regular diet 6 hours after delivery. At 6 hours after surgery, the patient was out of bed and moving; walks around the nursing unit were scheduled three times per day at minimum. For pain, patients were given a 1,000-mg acetaminophen tablet every 8 hours, a 600-mg ibuprofen tablet every 6 hours, and dextromethorphan 30 mg/mL every 8 hours, with oral oxycodone 5 mg administered after physician evaluation for breakthrough pain.
Overall, there were 3,679 cesarean deliveries in the study, which included 2,171 deliveries prior to ERAS implementation and 1,508 cesarean deliveries after implementation. Patients with a scheduled cesarean delivery prior to ERAS implementation received no consistent educational program for anticipating cesarean delivery. After implementation, those patients with scheduled cesarean delivery received the full preoperative, intraoperative, and postoperative pathway, while emergent cesarean cases included the intraoperative management and postoperative care, but did not contain the preoperative component.
Improved outcomes after ERAS
The researchers found a significant decrease in the use of opioids after implementing ERAS at the center, with 24% of patients receiving opioids after ERAS, compared with 84% of patients prior to ERAS (odds ratio, 16.8; 95% confidence interval, 14.3-19.9; P < .001). These reductions in opioid use from the pre- and postimplementation periods were similar for patients with scheduled cesarean deliveries (85% vs. 27%; OR, 14.9; 95% CI, 12.2-18.3; P < .001) and emergent cesarean deliveries (83% vs. 19%; OR, 21.4; 95% CI, 16.1-28.7; P < .001).
There was also a significant reduction in total morphine milligram equivalents (MME) for patients who received opioids after ERAS (median, 15.0 MME), compared with before (median, 56.5 MME) implementing ERAS (mean relative change, 0.32; 95% CI, 0.28-0.35; P < .001). These results also were significant among both scheduled (median 59.9 vs. 15.0 MME; mean relative change, 0.31; 95% CI, 0.27-0.36; P < .001) and emergent (median 56.5 vs. 15.0 MME; mean relative change, 0.95; 95% CI, 0.89-1.01; P < .001) cesarean deliveries.
The overall length of stay after cesarean delivery significantly decreased after ERAS from an average of 3.2 days to 2.7 days (mean relative change, 0.82, 95% CI, 0.80-0.83; P < .001), and was significant in both scheduled (3.2 vs. 2.7 days; mean relative change, 0.83; 95% CI, 0.81-0.85; P < .001) and emergent (3.1 vs. 2.5 days; mean relative change, 0.80; 95% CI, 0.77-0.82; P < .001) groups. While the number of patients discharged within 2 days increased from 9% to 49% after ERAS implementation, there was no significant difference overall or in either group regarding 30-day readmission. The researchers also noted the median direct costs of cesarean delivery decreased by $349 per case after starting ERAS (mean relative change, 0.93; 95% CI, 0.91-0.95).
ERAS implementation lagging in obstetrics
In an interview, Iris Krishna, MD, MPH, a maternal-fetal medicine specialist at Emory University, Atlanta, said the ERAS approach has been used successfully in other surgical specialties but has “lagged” in obstetrics. “To date, there has been less attention in improving perioperative outcomes for women undergoing cesarean delivery, the most common abdominal surgery for women.”
Dr. Krishna said this study shows ERAS can be used in obstetrics to improve outcomes after cesarean section without increasing readmission rates. “Overall, this study demonstrates that ERAS can be successfully implemented for cesarean delivery as it has been for a variety of surgical specialties. ERAS for cesarean delivery can improve the quality of patient care while reducing health care costs.”
Women in the postpartum and postoperative period could benefit from ERAS as they recover from surgery and adjust to becoming a new mother, Dr. Krishna noted. “The goal of ERAS is to help patients return to physiological functioning as quickly as possible. Improving postoperative recovery can help with mother-infant bonding and breastfeeding.
“Implementation of a standardized approach for cesarean delivery has the potential to reduce health disparities and the disproportionately high rates of maternal morbidity and mortality in the United States,” she added. “ERAS for cesarean delivery also has the potential to address the opioid epidemic amongst reproductive-age women by improving postcesarean pain management and reducing opioid prescribing.”
Dr. Krishna also explained that an ERAS program would be feasible to implement in most centers. “It will require a shift of some elements of care from the inpatient to outpatient setting, but theoretically feasible as pregnant women frequently undergo many clinic visits during their pregnancy course.
“Education on ERAS for cesarean delivery can be implemented into prenatal care visits. ERAS implementation will also require a multidisciplinary team approach that includes obstetrics, anesthesia, nursing, pharmacy, pediatrics – all key stakeholders that will need to ‘buy in’ or be willing to support the protocol to ensure its success. As in this study, it would be helpful for hospitals to have an ERAS coordinator to champion and ensure compliance of protocol.”
Dr. Miller reported that he has received payments from the Coventus Professional Liability Insurance: Risk Management Committee and the New Jersey Board of Medical Examiners. The other authors reported no relevant conflicts of interest. Dr. Krishna reported no relevant conflicts of interest.
SOURCE: Mullman L et al. Obstet Gynecol. 2020 Oct. doi: 10.1097/AOG.0000000000004023.
FROM OBSTETRICS & GYNECOLOGY
FDA updates info on postmarketing surveillance study of Essure
The Food and Drug Administration has updated its page on Essure information for patients and health care providers to add additional information on adverse events reported by its manufacturer.
Essure was a permanent implantable birth control device approved by the FDA in 2002. FDA ordered Bayer in 2016 to conduct a postmarket surveillance study of Essure following reports of safety concerns, and expanded the study from 3 years to 5 years in 2018. Bayer voluntarily removed Essure from the market at the end of 2018, citing low sales after a “black box” warning was placed on the device. All devices were returned to the company by the end of 2019.
Bayer is required to report variances in Medical Device Reporting (MDR) requirements of Essure related to litigation to the FDA, which includes adverse events such death, serious injury, and “malfunction that would be likely to cause or contribute to a death or serious injury if the malfunction were to recur.” The reports are limited to events Bayer becomes aware of between November 2016 and November 2020. Bayer will continue to provide these reports until April 2021.
The FDA emphasized that the collected data are based on social media reports and already may be reported to the FDA, rather than being a collection of new events. “The limited information provided in the reports prevents the ability to draw any conclusions as to whether the device, or its removal, caused or contributed to any of the events in the reports,” Benjamin Fisher, PhD, director of the Reproductive, Gastro-Renal, Urological, General Hospital Device and Human Factors Office in the Center for Devices and Radiological Health, said in an FDA In Brief statement on Aug. 11.
The FDA first uploaded an Essure MDR variance spreadsheet in August 2020, listing 1,453 events, consisting of 53 reports of deaths, 1,376 reports of serious injury, and 24 reports of device malfunction that occurred as of June 2020. In September 2020, FDA uploaded a second variance spreadsheet, which added another 1,934 events that occurred as of July.
Interim analysis of postmarketing surveillance study
An interim analysis of 1,128 patients from 67 centers in the Essure postmarket surveillance study, which compared women who received Essure with those who received laparoscopic tubal sterilization, revealed that 94.6% (265 of 280 patients) in the Essure group had a successful implantation of the device, compared with 99.6% of women who achieved bilateral tubal occlusion from laparoscopic tubal sterilization.
Regarding safety, 9.1% of women in the Essure group and 4.5% in the laparoscopic tubal sterilization group reported chronic lower abdominal and/or pelvic pain, and 16.3% in the Essure group and 10.2% in the laparoscopic tubal sterilization group reported new or worsening abnormal uterine bleeding. In the Essure group, 22.3% of women said they experienced hypersensitivity, an allergic reaction, and new “autoimmune-like reactions” compared with 12.5% of women in the laparoscopic tubal sterilization group.
The interim analysis also showed 19.7% of women in the Essure group and 3.0% in the laparoscopic tubal sterilization group underwent gynecologic surgical procedures, which were “driven primarily by Essure removal and endometrial ablation procedures in Essure patients.” Device removal occurred in 6.8% of women with the Essure device.
Consistent data on Essure
An FDA search of the Manufacturer and User Facility Device Experience (MAUDE) database in January of 2020 revealed 47,856 medical device reports of Essure between November 2002 and December 2019. The most common adverse events observed during this period were:
- Pain or abdominal pain (32,901 cases).
- Heavy or irregular menses (14,573 cases). Headache (8,570 cases).
- Device fragment or foreign body in a patient (8,501 cases).
- Perforation (7,825 cases).
- Fatigue (7,083 cases).
- Gain or loss in weight (5,980 cases).
- Anxiety and/or depression (5,366 cases).
- Rash and/or hypersensitivity (5,077 cases)
- Hair loss (4,999 cases).
Problems with the device itself included reports of:
- Device incompatibility such as an allergy (7,515 cases).
- The device migrating (4,535 cases).
- The device breaking or fracturing (2,297 cases).
- The device dislodging or dislocating (1,797 cases).
- Improper operation including implant failure and pregnancy (1,058 cases).
In 2019, Essure received 15,083 medical device reports, an increase from 6,000 reports in 2018 and 11,854 reports in 2017.
To date, nearly 39,000 women in the United States have made claims to injuries related to the Essure device. In August, Bayer announced it would pay approximately $1.6 billion U.S. dollars to settle 90% of these cases in exchange for claimants to “dismiss their cases or not file.” Bayer also said in a press release that the settlement is not an admission of wrongdoing or liability on the part of the company.
In an interview, Catherine Cansino, MD, MPH, of the department of obstetrics and gynecology at the University of California, Davis, said the latest adverse event reports show “consistent info from [the] MAUDE database when comparing 2019 to previous years, highlighting most common problems related to pain and heavy or irregular bleeding.”
She emphasized ob.gyns with patients who have an Essure device should “consider Essure-related etiology that may necessitate device removal when evaluating patients with gynecological problems, especially with regard to abdominal/pelvic pain and heavy/irregular bleeding.”
Dr. Cansino reported no relevant financial disclosures. She is a member of the Ob.Gyn. News Editorial Advisory Board.
The Food and Drug Administration has updated its page on Essure information for patients and health care providers to add additional information on adverse events reported by its manufacturer.
Essure was a permanent implantable birth control device approved by the FDA in 2002. FDA ordered Bayer in 2016 to conduct a postmarket surveillance study of Essure following reports of safety concerns, and expanded the study from 3 years to 5 years in 2018. Bayer voluntarily removed Essure from the market at the end of 2018, citing low sales after a “black box” warning was placed on the device. All devices were returned to the company by the end of 2019.
Bayer is required to report variances in Medical Device Reporting (MDR) requirements of Essure related to litigation to the FDA, which includes adverse events such death, serious injury, and “malfunction that would be likely to cause or contribute to a death or serious injury if the malfunction were to recur.” The reports are limited to events Bayer becomes aware of between November 2016 and November 2020. Bayer will continue to provide these reports until April 2021.
The FDA emphasized that the collected data are based on social media reports and already may be reported to the FDA, rather than being a collection of new events. “The limited information provided in the reports prevents the ability to draw any conclusions as to whether the device, or its removal, caused or contributed to any of the events in the reports,” Benjamin Fisher, PhD, director of the Reproductive, Gastro-Renal, Urological, General Hospital Device and Human Factors Office in the Center for Devices and Radiological Health, said in an FDA In Brief statement on Aug. 11.
The FDA first uploaded an Essure MDR variance spreadsheet in August 2020, listing 1,453 events, consisting of 53 reports of deaths, 1,376 reports of serious injury, and 24 reports of device malfunction that occurred as of June 2020. In September 2020, FDA uploaded a second variance spreadsheet, which added another 1,934 events that occurred as of July.
Interim analysis of postmarketing surveillance study
An interim analysis of 1,128 patients from 67 centers in the Essure postmarket surveillance study, which compared women who received Essure with those who received laparoscopic tubal sterilization, revealed that 94.6% (265 of 280 patients) in the Essure group had a successful implantation of the device, compared with 99.6% of women who achieved bilateral tubal occlusion from laparoscopic tubal sterilization.
Regarding safety, 9.1% of women in the Essure group and 4.5% in the laparoscopic tubal sterilization group reported chronic lower abdominal and/or pelvic pain, and 16.3% in the Essure group and 10.2% in the laparoscopic tubal sterilization group reported new or worsening abnormal uterine bleeding. In the Essure group, 22.3% of women said they experienced hypersensitivity, an allergic reaction, and new “autoimmune-like reactions” compared with 12.5% of women in the laparoscopic tubal sterilization group.
The interim analysis also showed 19.7% of women in the Essure group and 3.0% in the laparoscopic tubal sterilization group underwent gynecologic surgical procedures, which were “driven primarily by Essure removal and endometrial ablation procedures in Essure patients.” Device removal occurred in 6.8% of women with the Essure device.
Consistent data on Essure
An FDA search of the Manufacturer and User Facility Device Experience (MAUDE) database in January of 2020 revealed 47,856 medical device reports of Essure between November 2002 and December 2019. The most common adverse events observed during this period were:
- Pain or abdominal pain (32,901 cases).
- Heavy or irregular menses (14,573 cases). Headache (8,570 cases).
- Device fragment or foreign body in a patient (8,501 cases).
- Perforation (7,825 cases).
- Fatigue (7,083 cases).
- Gain or loss in weight (5,980 cases).
- Anxiety and/or depression (5,366 cases).
- Rash and/or hypersensitivity (5,077 cases)
- Hair loss (4,999 cases).
Problems with the device itself included reports of:
- Device incompatibility such as an allergy (7,515 cases).
- The device migrating (4,535 cases).
- The device breaking or fracturing (2,297 cases).
- The device dislodging or dislocating (1,797 cases).
- Improper operation including implant failure and pregnancy (1,058 cases).
In 2019, Essure received 15,083 medical device reports, an increase from 6,000 reports in 2018 and 11,854 reports in 2017.
To date, nearly 39,000 women in the United States have made claims to injuries related to the Essure device. In August, Bayer announced it would pay approximately $1.6 billion U.S. dollars to settle 90% of these cases in exchange for claimants to “dismiss their cases or not file.” Bayer also said in a press release that the settlement is not an admission of wrongdoing or liability on the part of the company.
In an interview, Catherine Cansino, MD, MPH, of the department of obstetrics and gynecology at the University of California, Davis, said the latest adverse event reports show “consistent info from [the] MAUDE database when comparing 2019 to previous years, highlighting most common problems related to pain and heavy or irregular bleeding.”
She emphasized ob.gyns with patients who have an Essure device should “consider Essure-related etiology that may necessitate device removal when evaluating patients with gynecological problems, especially with regard to abdominal/pelvic pain and heavy/irregular bleeding.”
Dr. Cansino reported no relevant financial disclosures. She is a member of the Ob.Gyn. News Editorial Advisory Board.
The Food and Drug Administration has updated its page on Essure information for patients and health care providers to add additional information on adverse events reported by its manufacturer.
Essure was a permanent implantable birth control device approved by the FDA in 2002. FDA ordered Bayer in 2016 to conduct a postmarket surveillance study of Essure following reports of safety concerns, and expanded the study from 3 years to 5 years in 2018. Bayer voluntarily removed Essure from the market at the end of 2018, citing low sales after a “black box” warning was placed on the device. All devices were returned to the company by the end of 2019.
Bayer is required to report variances in Medical Device Reporting (MDR) requirements of Essure related to litigation to the FDA, which includes adverse events such death, serious injury, and “malfunction that would be likely to cause or contribute to a death or serious injury if the malfunction were to recur.” The reports are limited to events Bayer becomes aware of between November 2016 and November 2020. Bayer will continue to provide these reports until April 2021.
The FDA emphasized that the collected data are based on social media reports and already may be reported to the FDA, rather than being a collection of new events. “The limited information provided in the reports prevents the ability to draw any conclusions as to whether the device, or its removal, caused or contributed to any of the events in the reports,” Benjamin Fisher, PhD, director of the Reproductive, Gastro-Renal, Urological, General Hospital Device and Human Factors Office in the Center for Devices and Radiological Health, said in an FDA In Brief statement on Aug. 11.
The FDA first uploaded an Essure MDR variance spreadsheet in August 2020, listing 1,453 events, consisting of 53 reports of deaths, 1,376 reports of serious injury, and 24 reports of device malfunction that occurred as of June 2020. In September 2020, FDA uploaded a second variance spreadsheet, which added another 1,934 events that occurred as of July.
Interim analysis of postmarketing surveillance study
An interim analysis of 1,128 patients from 67 centers in the Essure postmarket surveillance study, which compared women who received Essure with those who received laparoscopic tubal sterilization, revealed that 94.6% (265 of 280 patients) in the Essure group had a successful implantation of the device, compared with 99.6% of women who achieved bilateral tubal occlusion from laparoscopic tubal sterilization.
Regarding safety, 9.1% of women in the Essure group and 4.5% in the laparoscopic tubal sterilization group reported chronic lower abdominal and/or pelvic pain, and 16.3% in the Essure group and 10.2% in the laparoscopic tubal sterilization group reported new or worsening abnormal uterine bleeding. In the Essure group, 22.3% of women said they experienced hypersensitivity, an allergic reaction, and new “autoimmune-like reactions” compared with 12.5% of women in the laparoscopic tubal sterilization group.
The interim analysis also showed 19.7% of women in the Essure group and 3.0% in the laparoscopic tubal sterilization group underwent gynecologic surgical procedures, which were “driven primarily by Essure removal and endometrial ablation procedures in Essure patients.” Device removal occurred in 6.8% of women with the Essure device.
Consistent data on Essure
An FDA search of the Manufacturer and User Facility Device Experience (MAUDE) database in January of 2020 revealed 47,856 medical device reports of Essure between November 2002 and December 2019. The most common adverse events observed during this period were:
- Pain or abdominal pain (32,901 cases).
- Heavy or irregular menses (14,573 cases). Headache (8,570 cases).
- Device fragment or foreign body in a patient (8,501 cases).
- Perforation (7,825 cases).
- Fatigue (7,083 cases).
- Gain or loss in weight (5,980 cases).
- Anxiety and/or depression (5,366 cases).
- Rash and/or hypersensitivity (5,077 cases)
- Hair loss (4,999 cases).
Problems with the device itself included reports of:
- Device incompatibility such as an allergy (7,515 cases).
- The device migrating (4,535 cases).
- The device breaking or fracturing (2,297 cases).
- The device dislodging or dislocating (1,797 cases).
- Improper operation including implant failure and pregnancy (1,058 cases).
In 2019, Essure received 15,083 medical device reports, an increase from 6,000 reports in 2018 and 11,854 reports in 2017.
To date, nearly 39,000 women in the United States have made claims to injuries related to the Essure device. In August, Bayer announced it would pay approximately $1.6 billion U.S. dollars to settle 90% of these cases in exchange for claimants to “dismiss their cases or not file.” Bayer also said in a press release that the settlement is not an admission of wrongdoing or liability on the part of the company.
In an interview, Catherine Cansino, MD, MPH, of the department of obstetrics and gynecology at the University of California, Davis, said the latest adverse event reports show “consistent info from [the] MAUDE database when comparing 2019 to previous years, highlighting most common problems related to pain and heavy or irregular bleeding.”
She emphasized ob.gyns with patients who have an Essure device should “consider Essure-related etiology that may necessitate device removal when evaluating patients with gynecological problems, especially with regard to abdominal/pelvic pain and heavy/irregular bleeding.”
Dr. Cansino reported no relevant financial disclosures. She is a member of the Ob.Gyn. News Editorial Advisory Board.
Shingrix effective in older adults with preexisting immune-mediated disorders
The adjuvanted recombinant zoster vaccine Shingrix appears to be effective in older adults with autoimmune diseases who are not receiving treatment regimens that suppress the immune system, according to a post hoc analysis of patients in two clinical trials.
A two-dose regimen of Shingrix was effective in 90.5% of a subset of patients in two phase 3 clinical trials of adults who were aged at least 50 years, according to Alemnew F. Dagnew, MD, of GlaxoSmithKline and colleagues. The lowest rates of effectiveness with Shingrix, for patients aged between 70-79 years, was 84.4%, the researchers reported in Rheumatology.
The CDC recommends adults aged at least 50 years receive two doses of Shingrix to help prevent reoccurrence of herpes zoster, or Zostavax (zoster vaccine live) if adults are allergic to components of the Shingrix vaccine or have tested negative for varicella zoster virus immunity.
Dr. Dagnew and colleagues evaluated Shingrix in 983 patients who received two doses of Shingrix and 960 patients who received placebo from the ZOE-50 and ZOE-70 trials, where each dose was administered at least 2 months apart. The mean age of patients in both groups was 68.8 years in the Shingrix group and 69.4 years in the placebo group, and more than half of patients in both Shingrix (59.9%) and placebo groups (60.8%) were women. About 7% of the patients in two clinical trial had a pIMD.
At enrollment, the most common preexisting immune-mediated disorders (pIMDs) were psoriasis (215 patients taking Shingrix vs. 239 patients on placebo), spondyloarthropathy (109 patients taking Shingrix vs. 89 patients on placebo), rheumatoid arthritis (96 patients taking Shingrix vs. 94 patients on placebo), and celiac disease (41 patients taking Shingrix vs. 34 patients on placebo). Dr. Dagnew and colleagues examined the subgroup of patients with pIMDs for safety and vaccine efficacy, which was defined as not developing herpes zoster before the second dose.
Overall, the efficacy of Shingrix was 90.5% across all age groups (95% confidence interval, 73.5%-97.5%), with the group aged between 70-79 years having the lowest rate of effectiveness (95% CI, 30.8%-98.3%). The rate of severe adverse events was 14.6% in the Shingrix group and 11.7% in the placebo group between the first Shingrix dose and for up to 1 year after the second dose. The most common adverse events were infections and infestations as well as cardiac disorders. “Our data show a balance between study groups in the frequency and nature of SAEs, confirming the favorable safety profile of [Shingrix] in populations with pIMDs,” Dr. Dagnew and colleagues wrote.
The researchers acknowledged that the ZOE-50/70 studies were underpowered to detect the efficacy and safety of Shingrix in individuals with pIMDs but said that the large number of participants in the studies let them estimate efficacy and adverse events for this subgroup. They also noted there was no randomization of pIMDs at enrollment, even though pIMDs occurred at similar rates between Shingrix and placebo groups.
This study was funded by GlaxoSmithKline; the company helped with conducting and analyzing the study and also provided the costs associated with publishing it. Five authors reported being an employee of GlaxoSmithKline during the time the work was conducted, and four of the five own stock in the company. One author is now an employee of UCB. One author reported having served on the advisory boards for Merck Sharp & Dohme, GlaxoSmithKline, and Curevo.
SOURCE: Dagnew AF et al. Rheumatology. 2020 Sep 10. doi: 10.1093/rheumatology/keaa424.
The adjuvanted recombinant zoster vaccine Shingrix appears to be effective in older adults with autoimmune diseases who are not receiving treatment regimens that suppress the immune system, according to a post hoc analysis of patients in two clinical trials.
A two-dose regimen of Shingrix was effective in 90.5% of a subset of patients in two phase 3 clinical trials of adults who were aged at least 50 years, according to Alemnew F. Dagnew, MD, of GlaxoSmithKline and colleagues. The lowest rates of effectiveness with Shingrix, for patients aged between 70-79 years, was 84.4%, the researchers reported in Rheumatology.
The CDC recommends adults aged at least 50 years receive two doses of Shingrix to help prevent reoccurrence of herpes zoster, or Zostavax (zoster vaccine live) if adults are allergic to components of the Shingrix vaccine or have tested negative for varicella zoster virus immunity.
Dr. Dagnew and colleagues evaluated Shingrix in 983 patients who received two doses of Shingrix and 960 patients who received placebo from the ZOE-50 and ZOE-70 trials, where each dose was administered at least 2 months apart. The mean age of patients in both groups was 68.8 years in the Shingrix group and 69.4 years in the placebo group, and more than half of patients in both Shingrix (59.9%) and placebo groups (60.8%) were women. About 7% of the patients in two clinical trial had a pIMD.
At enrollment, the most common preexisting immune-mediated disorders (pIMDs) were psoriasis (215 patients taking Shingrix vs. 239 patients on placebo), spondyloarthropathy (109 patients taking Shingrix vs. 89 patients on placebo), rheumatoid arthritis (96 patients taking Shingrix vs. 94 patients on placebo), and celiac disease (41 patients taking Shingrix vs. 34 patients on placebo). Dr. Dagnew and colleagues examined the subgroup of patients with pIMDs for safety and vaccine efficacy, which was defined as not developing herpes zoster before the second dose.
Overall, the efficacy of Shingrix was 90.5% across all age groups (95% confidence interval, 73.5%-97.5%), with the group aged between 70-79 years having the lowest rate of effectiveness (95% CI, 30.8%-98.3%). The rate of severe adverse events was 14.6% in the Shingrix group and 11.7% in the placebo group between the first Shingrix dose and for up to 1 year after the second dose. The most common adverse events were infections and infestations as well as cardiac disorders. “Our data show a balance between study groups in the frequency and nature of SAEs, confirming the favorable safety profile of [Shingrix] in populations with pIMDs,” Dr. Dagnew and colleagues wrote.
The researchers acknowledged that the ZOE-50/70 studies were underpowered to detect the efficacy and safety of Shingrix in individuals with pIMDs but said that the large number of participants in the studies let them estimate efficacy and adverse events for this subgroup. They also noted there was no randomization of pIMDs at enrollment, even though pIMDs occurred at similar rates between Shingrix and placebo groups.
This study was funded by GlaxoSmithKline; the company helped with conducting and analyzing the study and also provided the costs associated with publishing it. Five authors reported being an employee of GlaxoSmithKline during the time the work was conducted, and four of the five own stock in the company. One author is now an employee of UCB. One author reported having served on the advisory boards for Merck Sharp & Dohme, GlaxoSmithKline, and Curevo.
SOURCE: Dagnew AF et al. Rheumatology. 2020 Sep 10. doi: 10.1093/rheumatology/keaa424.
The adjuvanted recombinant zoster vaccine Shingrix appears to be effective in older adults with autoimmune diseases who are not receiving treatment regimens that suppress the immune system, according to a post hoc analysis of patients in two clinical trials.
A two-dose regimen of Shingrix was effective in 90.5% of a subset of patients in two phase 3 clinical trials of adults who were aged at least 50 years, according to Alemnew F. Dagnew, MD, of GlaxoSmithKline and colleagues. The lowest rates of effectiveness with Shingrix, for patients aged between 70-79 years, was 84.4%, the researchers reported in Rheumatology.
The CDC recommends adults aged at least 50 years receive two doses of Shingrix to help prevent reoccurrence of herpes zoster, or Zostavax (zoster vaccine live) if adults are allergic to components of the Shingrix vaccine or have tested negative for varicella zoster virus immunity.
Dr. Dagnew and colleagues evaluated Shingrix in 983 patients who received two doses of Shingrix and 960 patients who received placebo from the ZOE-50 and ZOE-70 trials, where each dose was administered at least 2 months apart. The mean age of patients in both groups was 68.8 years in the Shingrix group and 69.4 years in the placebo group, and more than half of patients in both Shingrix (59.9%) and placebo groups (60.8%) were women. About 7% of the patients in two clinical trial had a pIMD.
At enrollment, the most common preexisting immune-mediated disorders (pIMDs) were psoriasis (215 patients taking Shingrix vs. 239 patients on placebo), spondyloarthropathy (109 patients taking Shingrix vs. 89 patients on placebo), rheumatoid arthritis (96 patients taking Shingrix vs. 94 patients on placebo), and celiac disease (41 patients taking Shingrix vs. 34 patients on placebo). Dr. Dagnew and colleagues examined the subgroup of patients with pIMDs for safety and vaccine efficacy, which was defined as not developing herpes zoster before the second dose.
Overall, the efficacy of Shingrix was 90.5% across all age groups (95% confidence interval, 73.5%-97.5%), with the group aged between 70-79 years having the lowest rate of effectiveness (95% CI, 30.8%-98.3%). The rate of severe adverse events was 14.6% in the Shingrix group and 11.7% in the placebo group between the first Shingrix dose and for up to 1 year after the second dose. The most common adverse events were infections and infestations as well as cardiac disorders. “Our data show a balance between study groups in the frequency and nature of SAEs, confirming the favorable safety profile of [Shingrix] in populations with pIMDs,” Dr. Dagnew and colleagues wrote.
The researchers acknowledged that the ZOE-50/70 studies were underpowered to detect the efficacy and safety of Shingrix in individuals with pIMDs but said that the large number of participants in the studies let them estimate efficacy and adverse events for this subgroup. They also noted there was no randomization of pIMDs at enrollment, even though pIMDs occurred at similar rates between Shingrix and placebo groups.
This study was funded by GlaxoSmithKline; the company helped with conducting and analyzing the study and also provided the costs associated with publishing it. Five authors reported being an employee of GlaxoSmithKline during the time the work was conducted, and four of the five own stock in the company. One author is now an employee of UCB. One author reported having served on the advisory boards for Merck Sharp & Dohme, GlaxoSmithKline, and Curevo.
SOURCE: Dagnew AF et al. Rheumatology. 2020 Sep 10. doi: 10.1093/rheumatology/keaa424.
FROM RHEUMATOLOGY
Nearly half of brachial plexus injury cases occur without shoulder dystocia
according to research published in Obstetrics & Gynecology.
Grace J. Johnson, MD, and colleagues at Baylor College of Medicine in Houston performed a medical review of 41,525 deliveries at Texas Children’s Hospital between March 2012 and July 2019, identifying cases of brachial plexus injury, with and without shoulder dystocia, occurring and persisting. The researchers also evaluated whether clinical experience (5 years or fewer, 6-15 years, or more than 15 years since training) and education impacted the risk of children developing shoulder dystocia or brachial plexus injury.
There were 547 cases of shoulder dystocia in 26,163 vaginal births (2.1%) and 9 cases in 15,362 cesarean births (0.06%), while 33 cases of brachial plexus injury occurred overall. Nearly all brachial plexus injuries were in vaginal deliveries (30 cases; 0.1%), while 3 cases occurred in cesarean deliveries (0.02%). Of these, 14 cases (42%) of brachial plexus injury did not co-occur with shoulder dystocia. Brachial plexus injury that persisted to discharge was similar for children with shoulder dystocia (17 of 19 cases; 89%) and without shoulder dystocia (10 of 14 cases; 71%). In the 27 children with persistent brachial plexus injury, 2 of 23 children who received follow-up care continued to experience persistent brachial plexus injury at 9 months (1 case with shoulder dystocia) and 12 months (1 case without shoulder dystocia).
“The frequent co-occurrence of shoulder dystocia and brachial plexus injury coupled with the equally frequent occurrence of isolated brachial plexus injury suggests that both brachial plexus injury and shoulder dystocia often reflect two causally unrelated complications of uterine forces driving a fetus through the birth canal in the presence of disproportion between the passage and the shoulder girdle of the passenger,” Dr. Johnson and colleagues wrote.
Results unchanged by clinician experience
Factors that impacted the risk of brachial plexus injury in children without shoulder dystocia were lack of maternal diabetes (0 women vs. 6 women; P = .03) and second-stage labor length (mean 103 minutes vs. 53 minutes; P = .08). Dr. Johnson and colleagues found no significant between-group differences regarding operative delivery, maternal age, or gestational age.
The researchers also examined the experience of the clinician who delivered children with brachial plexus injuries, and discovered there were no significant differences in children who had transient as opposed to persistent brachial plexus injury based on the number of years a clinician had been in practice (P = .97). There also were no significant changes in the “ratios of brachial plexus injury per total deliveries, brachial plexus injury per vaginal deliveries, and brachial plexus injury per shoulder dystocia” despite the presence of education and training for shoulder dystocia.
Questions require further study
Torri Metz, MD, MS, a maternal-fetal medicine subspecialist and associate professor of obstetrics and gynecology at University of Utah Health in Salt Lake City, said in an interview that the review by Johnson and colleagues was able to address limitations in previous studies by looking at the medical records of shoulder dystocia cases at a single tertiary care center.
“Brachial plexus injury occurs both with and without a diagnosis of shoulder dystocia. The finding that the non–shoulder dystocia brachial plexus injuries were associated with a longer second stage of labor suggests that these injuries can occur even prior to delivery of the fetal head and are often not related to maneuvers employed by an obstetrician during delivery,” Dr. Metz said.
The findings that brachial plexus injury severity was unrelated to clinician experience suggests “the occurrence, severity, and persistence of brachial plexus injury may be unrelated to maneuvers by the practitioner at the time of delivery,” she said.
Although Johnson et al. found education and training initiatives did not significantly impact the ratio of brachial plexus injury cases, “importantly, there are likely many other benefits to shoulder dystocia simulation including team communication and comfort of the practitioner in an obstetrical emergency. Thus, the conclusion should not be that simulation training should be abandoned,” Dr. Metz explained.
The results of the study should be confirmed in future research, she noted. “Despite looking at all cases of shoulder dystocia at a tertiary center over a 7-year period, the incidence of brachial plexus injury is low enough that only 33 cases were evaluated. As such, many questions about obstetrical management and the risk of brachial plexus injury still require further study,” said Dr. Metz, who was asked to comment on the study.
The authors reported no relevant financial disclosures. Dr. Metz is an editorial board member for Obstetrics and Gynecology. She was not involved in the review of this manuscript or the decision to publish it.
SOURCE: Johnson GJ et al. Obstet Gynecol. 2020 Oct. doi: 10.1097/AOG.0000000000004013.
according to research published in Obstetrics & Gynecology.
Grace J. Johnson, MD, and colleagues at Baylor College of Medicine in Houston performed a medical review of 41,525 deliveries at Texas Children’s Hospital between March 2012 and July 2019, identifying cases of brachial plexus injury, with and without shoulder dystocia, occurring and persisting. The researchers also evaluated whether clinical experience (5 years or fewer, 6-15 years, or more than 15 years since training) and education impacted the risk of children developing shoulder dystocia or brachial plexus injury.
There were 547 cases of shoulder dystocia in 26,163 vaginal births (2.1%) and 9 cases in 15,362 cesarean births (0.06%), while 33 cases of brachial plexus injury occurred overall. Nearly all brachial plexus injuries were in vaginal deliveries (30 cases; 0.1%), while 3 cases occurred in cesarean deliveries (0.02%). Of these, 14 cases (42%) of brachial plexus injury did not co-occur with shoulder dystocia. Brachial plexus injury that persisted to discharge was similar for children with shoulder dystocia (17 of 19 cases; 89%) and without shoulder dystocia (10 of 14 cases; 71%). In the 27 children with persistent brachial plexus injury, 2 of 23 children who received follow-up care continued to experience persistent brachial plexus injury at 9 months (1 case with shoulder dystocia) and 12 months (1 case without shoulder dystocia).
“The frequent co-occurrence of shoulder dystocia and brachial plexus injury coupled with the equally frequent occurrence of isolated brachial plexus injury suggests that both brachial plexus injury and shoulder dystocia often reflect two causally unrelated complications of uterine forces driving a fetus through the birth canal in the presence of disproportion between the passage and the shoulder girdle of the passenger,” Dr. Johnson and colleagues wrote.
Results unchanged by clinician experience
Factors that impacted the risk of brachial plexus injury in children without shoulder dystocia were lack of maternal diabetes (0 women vs. 6 women; P = .03) and second-stage labor length (mean 103 minutes vs. 53 minutes; P = .08). Dr. Johnson and colleagues found no significant between-group differences regarding operative delivery, maternal age, or gestational age.
The researchers also examined the experience of the clinician who delivered children with brachial plexus injuries, and discovered there were no significant differences in children who had transient as opposed to persistent brachial plexus injury based on the number of years a clinician had been in practice (P = .97). There also were no significant changes in the “ratios of brachial plexus injury per total deliveries, brachial plexus injury per vaginal deliveries, and brachial plexus injury per shoulder dystocia” despite the presence of education and training for shoulder dystocia.
Questions require further study
Torri Metz, MD, MS, a maternal-fetal medicine subspecialist and associate professor of obstetrics and gynecology at University of Utah Health in Salt Lake City, said in an interview that the review by Johnson and colleagues was able to address limitations in previous studies by looking at the medical records of shoulder dystocia cases at a single tertiary care center.
“Brachial plexus injury occurs both with and without a diagnosis of shoulder dystocia. The finding that the non–shoulder dystocia brachial plexus injuries were associated with a longer second stage of labor suggests that these injuries can occur even prior to delivery of the fetal head and are often not related to maneuvers employed by an obstetrician during delivery,” Dr. Metz said.
The findings that brachial plexus injury severity was unrelated to clinician experience suggests “the occurrence, severity, and persistence of brachial plexus injury may be unrelated to maneuvers by the practitioner at the time of delivery,” she said.
Although Johnson et al. found education and training initiatives did not significantly impact the ratio of brachial plexus injury cases, “importantly, there are likely many other benefits to shoulder dystocia simulation including team communication and comfort of the practitioner in an obstetrical emergency. Thus, the conclusion should not be that simulation training should be abandoned,” Dr. Metz explained.
The results of the study should be confirmed in future research, she noted. “Despite looking at all cases of shoulder dystocia at a tertiary center over a 7-year period, the incidence of brachial plexus injury is low enough that only 33 cases were evaluated. As such, many questions about obstetrical management and the risk of brachial plexus injury still require further study,” said Dr. Metz, who was asked to comment on the study.
The authors reported no relevant financial disclosures. Dr. Metz is an editorial board member for Obstetrics and Gynecology. She was not involved in the review of this manuscript or the decision to publish it.
SOURCE: Johnson GJ et al. Obstet Gynecol. 2020 Oct. doi: 10.1097/AOG.0000000000004013.
according to research published in Obstetrics & Gynecology.
Grace J. Johnson, MD, and colleagues at Baylor College of Medicine in Houston performed a medical review of 41,525 deliveries at Texas Children’s Hospital between March 2012 and July 2019, identifying cases of brachial plexus injury, with and without shoulder dystocia, occurring and persisting. The researchers also evaluated whether clinical experience (5 years or fewer, 6-15 years, or more than 15 years since training) and education impacted the risk of children developing shoulder dystocia or brachial plexus injury.
There were 547 cases of shoulder dystocia in 26,163 vaginal births (2.1%) and 9 cases in 15,362 cesarean births (0.06%), while 33 cases of brachial plexus injury occurred overall. Nearly all brachial plexus injuries were in vaginal deliveries (30 cases; 0.1%), while 3 cases occurred in cesarean deliveries (0.02%). Of these, 14 cases (42%) of brachial plexus injury did not co-occur with shoulder dystocia. Brachial plexus injury that persisted to discharge was similar for children with shoulder dystocia (17 of 19 cases; 89%) and without shoulder dystocia (10 of 14 cases; 71%). In the 27 children with persistent brachial plexus injury, 2 of 23 children who received follow-up care continued to experience persistent brachial plexus injury at 9 months (1 case with shoulder dystocia) and 12 months (1 case without shoulder dystocia).
“The frequent co-occurrence of shoulder dystocia and brachial plexus injury coupled with the equally frequent occurrence of isolated brachial plexus injury suggests that both brachial plexus injury and shoulder dystocia often reflect two causally unrelated complications of uterine forces driving a fetus through the birth canal in the presence of disproportion between the passage and the shoulder girdle of the passenger,” Dr. Johnson and colleagues wrote.
Results unchanged by clinician experience
Factors that impacted the risk of brachial plexus injury in children without shoulder dystocia were lack of maternal diabetes (0 women vs. 6 women; P = .03) and second-stage labor length (mean 103 minutes vs. 53 minutes; P = .08). Dr. Johnson and colleagues found no significant between-group differences regarding operative delivery, maternal age, or gestational age.
The researchers also examined the experience of the clinician who delivered children with brachial plexus injuries, and discovered there were no significant differences in children who had transient as opposed to persistent brachial plexus injury based on the number of years a clinician had been in practice (P = .97). There also were no significant changes in the “ratios of brachial plexus injury per total deliveries, brachial plexus injury per vaginal deliveries, and brachial plexus injury per shoulder dystocia” despite the presence of education and training for shoulder dystocia.
Questions require further study
Torri Metz, MD, MS, a maternal-fetal medicine subspecialist and associate professor of obstetrics and gynecology at University of Utah Health in Salt Lake City, said in an interview that the review by Johnson and colleagues was able to address limitations in previous studies by looking at the medical records of shoulder dystocia cases at a single tertiary care center.
“Brachial plexus injury occurs both with and without a diagnosis of shoulder dystocia. The finding that the non–shoulder dystocia brachial plexus injuries were associated with a longer second stage of labor suggests that these injuries can occur even prior to delivery of the fetal head and are often not related to maneuvers employed by an obstetrician during delivery,” Dr. Metz said.
The findings that brachial plexus injury severity was unrelated to clinician experience suggests “the occurrence, severity, and persistence of brachial plexus injury may be unrelated to maneuvers by the practitioner at the time of delivery,” she said.
Although Johnson et al. found education and training initiatives did not significantly impact the ratio of brachial plexus injury cases, “importantly, there are likely many other benefits to shoulder dystocia simulation including team communication and comfort of the practitioner in an obstetrical emergency. Thus, the conclusion should not be that simulation training should be abandoned,” Dr. Metz explained.
The results of the study should be confirmed in future research, she noted. “Despite looking at all cases of shoulder dystocia at a tertiary center over a 7-year period, the incidence of brachial plexus injury is low enough that only 33 cases were evaluated. As such, many questions about obstetrical management and the risk of brachial plexus injury still require further study,” said Dr. Metz, who was asked to comment on the study.
The authors reported no relevant financial disclosures. Dr. Metz is an editorial board member for Obstetrics and Gynecology. She was not involved in the review of this manuscript or the decision to publish it.
SOURCE: Johnson GJ et al. Obstet Gynecol. 2020 Oct. doi: 10.1097/AOG.0000000000004013.
FROM OBSTETRICS & GYNECOLOGY
