Mental Health

When a recent study from Columbia University reported that suicide and self-harm were nearly four times more likely in adults with autism spectrum disorder (ASD) than in the general population, the findings were sobering. But to many in the field, they were not surprising.

Previous analyses showed individuals with ASD were up to six times more likely to attempt suicide and nearly eight times as likely to succeed. However, the recent study published in JAMA Network Open is one of only a few on self-harm and suicide in autism spectrum disorder (ASD) to include a focus on adults.

“Previously there was relatively little information about adults with autism in general and on injury risk among adults with autism specifically,” study investigator Guohua Li, DrPH, MD, professor of epidemiology at Columbia University Mailman School of Public Health, New York, told this news organization.

“How to continue to provide social support and health care services to adults with autism presents a real challenge to society and is a public health issue,” Dr. Li said.
 

Falling off a ‘services cliff’

The ASD rate among children is at a record-high in the United States, which means the number of adults on the spectrum will also continue to climb. The incidence of adults with newly diagnosed ASD, who are sometimes described as the “lost generation,” is also increasing. Despite these realities, adults with ASD remain largely underserved and understudied.

The data that are available paint a concerning picture. Adolescents with ASD face a “services cliff” as they transition to adulthood and fall into a landscape with a serious lack of services, support, and clinicians trained to treat adults with ASD.

Compared with young adults without ASD, those on the spectrum have significantly lower college graduation rates, have a harder time finding and keeping a job, are more likely to have a co-occurring mental illness, and are far less likely to live independently.

Patients who receive their initial ASD diagnosis in adulthood face even greater challenges, including a significantly higher risk for suicide and self-harm than those who are diagnosed as children.

Before 2020, there were no national data on the number of U.S. adults with autism. That year, the Centers for Disease Control and Prevention released its first-ever report on adult autism prevalence, estimated to be 5.4 million.

That figure is almost definitely low, Matthew Maenner, PhD, autism surveillance team lead with the CDC’s National Center on Birth Defects and Developmental Disabilities, told this news organization.

Researchers use school and medical records to calculate child ASD rates, but counting adults with the disorder is far more difficult.

The CDC’s estimate was based on modeling reports from 2017 state-based population and mortality records and parent-reported survey data of U.S. children diagnosed with ASD. It was inexact, said Dr. Maenner, but it was a start.

“There are no good data on the prevalence of autism in adults. Anywhere,” he added.
 

Masking and camouflaging

Only about 3.5% of published studies on autism focus on adults, one review showed. In the recently published “The Lancet Commission on the future of care and clinical research in autism,” the section on research on adolescents and adults was a mere 189 words long.

“The brevity of this paragraph reflects the little data available in this area, not its importance” the authors write.

The recent report of higher self-harm risk in adults on the spectrum offers further evidence that “there just aren’t enough services and research on adults on [the] autism spectrum,” Edward S. Brodkin, MD, associate professor of psychiatry and director of the Adult Autism Spectrum Program at the University of Pennsylvania Perelman School of Medicine in Philadelphia, told this news organization.

Founded by Dr. Brodkin in 2013, the program provides ASD diagnostic and support services for adults with ASD. Like others in the field, Dr. Brodkin has noted a sharp increase in the number of previously undiagnosed adults seeking evaluation for possible ASD.

Many of his patients have recently diagnosed children and realized they share some of the same ASD symptoms. Others have long recognized traits common in autism but have engaged in what clinicians call “masking” or “camouflaging.” This is particularly true in women, who are diagnosed with autism at far lower rates than men.

The “lost generation” of adults who receive an ASD diagnosis later in life have a lower quality of life, studies suggest, and have the highest risk for suicide among all individuals with autism.

The recent study from Dr. Li and colleagues offers new evidence in both children and adults. But although the systematic review and meta-analysis of 31 studies showed high rates of self-injurious behavior and suicidality in both groups, Dr. Li said it’s the data on adults that was most alarming.

The OR of suicidality in children was 2.53, but the risk in adults was significantly higher, with an odds ratio (OR) of 3.84.

Adults were at greater risk for self-harm than children (OR, 1.45; 95% confidence interval, 1.04-2.03), with higher odds of self-injurious behavior (OR, 3.38; 95% CI, 2.54-4.50) and suicidality (OR, 3.84; 95% CI, 2.78-5.30), compared with children (OR, 2.99; 95% CI, 1.93-4.64 for self-injurious behavior, and OR, 2.53; 95% CI, 1.70-3.76 for suicidality).
 

Lightbulb moment?

Commenting for this news organization, Brenna Maddox, PhD, assistant professor of psychiatry at UNC Chapel Hill and co-chair of the American Association of Suicidology’s Autism and Suicide Committee, said “the sad reality” is that these findings won’t be surprising to many who work in the field.

“But for some clinicians and the public, this will be a lightbulb kind of moment, increasing awareness about a problem many of us have been talking about for a while,” said Dr. Maddox, who was not involved with the current research.

In January, she launched a 5-year, $9 million study to compare the efficacy of two suicide intervention programs in adolescents and young adults with autism.

The interventions use a well-known suicide prevention tool that has been newly modified for use in people with autism. One program would rely on the intervention alone, and the other would add a structured clinical follow-up.

“There has to be much more than awareness. We need more training for clinicians, we need more tools, we need to know which tools are going to work,” Dr. Maddox said.

Her new project could address all of those needs. Funded by the nonprofit Patient-Centered Outcomes Research Institute (PCORI), it will train 150 clinicians at centers in four states to identify suicidal risk among young adults with autism, utilize the prevention tool, and collect data on its efficacy alone or with follow-up.

Clinician training will begin this spring, and researchers hope to have the first patient data in the fall.
 

Scaling the ‘services cliff’

While Dr. Maddox’s study could yield a potential suicide prevention tool, she is quick to point out that the ultimate goal would be to have fewer people reach the point where such a tool is needed. However, that will take a multidisciplinary approach that begins with access to clinical care, including mental health care, she noted.

“Our mental health care system in general is not great for people on the spectrum, but it’s even worse for adults,” Dr. Maddox said.

Compared with neurotypical adults, adults with autism use more mental health services, have higher hospitalization rates, and are more likely to use primary care services, one recent study showed. The problem, Dr. Maddox notes, is that there are too few clinicians in those areas who are trained in autism care.

One way to address that issue is to mandate autism instruction in the medical curriculum, Catherine Lord, PhD, told this news organization when asked for comment. Dr. Lord is cochair of The Lancet commission on the future of care and clinical research in autism and professor of psychiatry at the Semel Institute for Neuroscience and Human Behavior at UCLA.

“Medical schools offer very little training on ASD, even in standard psychiatry training. For people who don’t specialize in child or adolescence psychiatry, there’s almost none,” Dr. Lord said.

Dr. Maddox agrees. One goal of the PCORI study is to turn their findings into a transportable training program, perhaps available via a webinar for clinicians, crisis center staff, and others who may encounter an adult with autism who is contemplating suicide.

“This is a life and death situation,” Dr. Maddox said. “We have to marshal every resource we have, and we have to do it now. We can’t waste time.”

Dr. Li’s study was funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development of the National Institutes of Health. Study authors and other sources reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

When a recent study from Columbia University reported that suicide and self-harm were nearly four times more likely in adults with autism spectrum disorder (ASD) than in the general population, the findings were sobering. But to many in the field, they were not surprising.

Previous analyses showed individuals with ASD were up to six times more likely to attempt suicide and nearly eight times as likely to succeed. However, the recent study published in JAMA Network Open is one of only a few on self-harm and suicide in autism spectrum disorder (ASD) to include a focus on adults.

“Previously there was relatively little information about adults with autism in general and on injury risk among adults with autism specifically,” study investigator Guohua Li, DrPH, MD, professor of epidemiology at Columbia University Mailman School of Public Health, New York, told this news organization.

“How to continue to provide social support and health care services to adults with autism presents a real challenge to society and is a public health issue,” Dr. Li said.
 

Falling off a ‘services cliff’

The ASD rate among children is at a record-high in the United States, which means the number of adults on the spectrum will also continue to climb. The incidence of adults with newly diagnosed ASD, who are sometimes described as the “lost generation,” is also increasing. Despite these realities, adults with ASD remain largely underserved and understudied.

The data that are available paint a concerning picture. Adolescents with ASD face a “services cliff” as they transition to adulthood and fall into a landscape with a serious lack of services, support, and clinicians trained to treat adults with ASD.

Compared with young adults without ASD, those on the spectrum have significantly lower college graduation rates, have a harder time finding and keeping a job, are more likely to have a co-occurring mental illness, and are far less likely to live independently.

Patients who receive their initial ASD diagnosis in adulthood face even greater challenges, including a significantly higher risk for suicide and self-harm than those who are diagnosed as children.

Before 2020, there were no national data on the number of U.S. adults with autism. That year, the Centers for Disease Control and Prevention released its first-ever report on adult autism prevalence, estimated to be 5.4 million.

That figure is almost definitely low, Matthew Maenner, PhD, autism surveillance team lead with the CDC’s National Center on Birth Defects and Developmental Disabilities, told this news organization.

Researchers use school and medical records to calculate child ASD rates, but counting adults with the disorder is far more difficult.

The CDC’s estimate was based on modeling reports from 2017 state-based population and mortality records and parent-reported survey data of U.S. children diagnosed with ASD. It was inexact, said Dr. Maenner, but it was a start.

“There are no good data on the prevalence of autism in adults. Anywhere,” he added.
 

Masking and camouflaging

Only about 3.5% of published studies on autism focus on adults, one review showed. In the recently published “The Lancet Commission on the future of care and clinical research in autism,” the section on research on adolescents and adults was a mere 189 words long.

“The brevity of this paragraph reflects the little data available in this area, not its importance” the authors write.

The recent report of higher self-harm risk in adults on the spectrum offers further evidence that “there just aren’t enough services and research on adults on [the] autism spectrum,” Edward S. Brodkin, MD, associate professor of psychiatry and director of the Adult Autism Spectrum Program at the University of Pennsylvania Perelman School of Medicine in Philadelphia, told this news organization.

Founded by Dr. Brodkin in 2013, the program provides ASD diagnostic and support services for adults with ASD. Like others in the field, Dr. Brodkin has noted a sharp increase in the number of previously undiagnosed adults seeking evaluation for possible ASD.

Many of his patients have recently diagnosed children and realized they share some of the same ASD symptoms. Others have long recognized traits common in autism but have engaged in what clinicians call “masking” or “camouflaging.” This is particularly true in women, who are diagnosed with autism at far lower rates than men.

The “lost generation” of adults who receive an ASD diagnosis later in life have a lower quality of life, studies suggest, and have the highest risk for suicide among all individuals with autism.

The recent study from Dr. Li and colleagues offers new evidence in both children and adults. But although the systematic review and meta-analysis of 31 studies showed high rates of self-injurious behavior and suicidality in both groups, Dr. Li said it’s the data on adults that was most alarming.

The OR of suicidality in children was 2.53, but the risk in adults was significantly higher, with an odds ratio (OR) of 3.84.

Adults were at greater risk for self-harm than children (OR, 1.45; 95% confidence interval, 1.04-2.03), with higher odds of self-injurious behavior (OR, 3.38; 95% CI, 2.54-4.50) and suicidality (OR, 3.84; 95% CI, 2.78-5.30), compared with children (OR, 2.99; 95% CI, 1.93-4.64 for self-injurious behavior, and OR, 2.53; 95% CI, 1.70-3.76 for suicidality).
 

Lightbulb moment?

Commenting for this news organization, Brenna Maddox, PhD, assistant professor of psychiatry at UNC Chapel Hill and co-chair of the American Association of Suicidology’s Autism and Suicide Committee, said “the sad reality” is that these findings won’t be surprising to many who work in the field.

“But for some clinicians and the public, this will be a lightbulb kind of moment, increasing awareness about a problem many of us have been talking about for a while,” said Dr. Maddox, who was not involved with the current research.

In January, she launched a 5-year, $9 million study to compare the efficacy of two suicide intervention programs in adolescents and young adults with autism.

The interventions use a well-known suicide prevention tool that has been newly modified for use in people with autism. One program would rely on the intervention alone, and the other would add a structured clinical follow-up.

“There has to be much more than awareness. We need more training for clinicians, we need more tools, we need to know which tools are going to work,” Dr. Maddox said.

Her new project could address all of those needs. Funded by the nonprofit Patient-Centered Outcomes Research Institute (PCORI), it will train 150 clinicians at centers in four states to identify suicidal risk among young adults with autism, utilize the prevention tool, and collect data on its efficacy alone or with follow-up.

Clinician training will begin this spring, and researchers hope to have the first patient data in the fall.
 

Scaling the ‘services cliff’

While Dr. Maddox’s study could yield a potential suicide prevention tool, she is quick to point out that the ultimate goal would be to have fewer people reach the point where such a tool is needed. However, that will take a multidisciplinary approach that begins with access to clinical care, including mental health care, she noted.

“Our mental health care system in general is not great for people on the spectrum, but it’s even worse for adults,” Dr. Maddox said.

Compared with neurotypical adults, adults with autism use more mental health services, have higher hospitalization rates, and are more likely to use primary care services, one recent study showed. The problem, Dr. Maddox notes, is that there are too few clinicians in those areas who are trained in autism care.

One way to address that issue is to mandate autism instruction in the medical curriculum, Catherine Lord, PhD, told this news organization when asked for comment. Dr. Lord is cochair of The Lancet commission on the future of care and clinical research in autism and professor of psychiatry at the Semel Institute for Neuroscience and Human Behavior at UCLA.

“Medical schools offer very little training on ASD, even in standard psychiatry training. For people who don’t specialize in child or adolescence psychiatry, there’s almost none,” Dr. Lord said.

Dr. Maddox agrees. One goal of the PCORI study is to turn their findings into a transportable training program, perhaps available via a webinar for clinicians, crisis center staff, and others who may encounter an adult with autism who is contemplating suicide.

“This is a life and death situation,” Dr. Maddox said. “We have to marshal every resource we have, and we have to do it now. We can’t waste time.”

Dr. Li’s study was funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development of the National Institutes of Health. Study authors and other sources reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

When a recent study from Columbia University reported that suicide and self-harm were nearly four times more likely in adults with autism spectrum disorder (ASD) than in the general population, the findings were sobering. But to many in the field, they were not surprising.

Previous analyses showed individuals with ASD were up to six times more likely to attempt suicide and nearly eight times as likely to succeed. However, the recent study published in JAMA Network Open is one of only a few on self-harm and suicide in autism spectrum disorder (ASD) to include a focus on adults.

“Previously there was relatively little information about adults with autism in general and on injury risk among adults with autism specifically,” study investigator Guohua Li, DrPH, MD, professor of epidemiology at Columbia University Mailman School of Public Health, New York, told this news organization.

“How to continue to provide social support and health care services to adults with autism presents a real challenge to society and is a public health issue,” Dr. Li said.
 

Falling off a ‘services cliff’

The ASD rate among children is at a record-high in the United States, which means the number of adults on the spectrum will also continue to climb. The incidence of adults with newly diagnosed ASD, who are sometimes described as the “lost generation,” is also increasing. Despite these realities, adults with ASD remain largely underserved and understudied.

The data that are available paint a concerning picture. Adolescents with ASD face a “services cliff” as they transition to adulthood and fall into a landscape with a serious lack of services, support, and clinicians trained to treat adults with ASD.

Compared with young adults without ASD, those on the spectrum have significantly lower college graduation rates, have a harder time finding and keeping a job, are more likely to have a co-occurring mental illness, and are far less likely to live independently.

Patients who receive their initial ASD diagnosis in adulthood face even greater challenges, including a significantly higher risk for suicide and self-harm than those who are diagnosed as children.

Before 2020, there were no national data on the number of U.S. adults with autism. That year, the Centers for Disease Control and Prevention released its first-ever report on adult autism prevalence, estimated to be 5.4 million.

That figure is almost definitely low, Matthew Maenner, PhD, autism surveillance team lead with the CDC’s National Center on Birth Defects and Developmental Disabilities, told this news organization.

Researchers use school and medical records to calculate child ASD rates, but counting adults with the disorder is far more difficult.

The CDC’s estimate was based on modeling reports from 2017 state-based population and mortality records and parent-reported survey data of U.S. children diagnosed with ASD. It was inexact, said Dr. Maenner, but it was a start.

“There are no good data on the prevalence of autism in adults. Anywhere,” he added.
 

Masking and camouflaging

Only about 3.5% of published studies on autism focus on adults, one review showed. In the recently published “The Lancet Commission on the future of care and clinical research in autism,” the section on research on adolescents and adults was a mere 189 words long.

“The brevity of this paragraph reflects the little data available in this area, not its importance” the authors write.

The recent report of higher self-harm risk in adults on the spectrum offers further evidence that “there just aren’t enough services and research on adults on [the] autism spectrum,” Edward S. Brodkin, MD, associate professor of psychiatry and director of the Adult Autism Spectrum Program at the University of Pennsylvania Perelman School of Medicine in Philadelphia, told this news organization.

Founded by Dr. Brodkin in 2013, the program provides ASD diagnostic and support services for adults with ASD. Like others in the field, Dr. Brodkin has noted a sharp increase in the number of previously undiagnosed adults seeking evaluation for possible ASD.

Many of his patients have recently diagnosed children and realized they share some of the same ASD symptoms. Others have long recognized traits common in autism but have engaged in what clinicians call “masking” or “camouflaging.” This is particularly true in women, who are diagnosed with autism at far lower rates than men.

The “lost generation” of adults who receive an ASD diagnosis later in life have a lower quality of life, studies suggest, and have the highest risk for suicide among all individuals with autism.

The recent study from Dr. Li and colleagues offers new evidence in both children and adults. But although the systematic review and meta-analysis of 31 studies showed high rates of self-injurious behavior and suicidality in both groups, Dr. Li said it’s the data on adults that was most alarming.

The OR of suicidality in children was 2.53, but the risk in adults was significantly higher, with an odds ratio (OR) of 3.84.

Adults were at greater risk for self-harm than children (OR, 1.45; 95% confidence interval, 1.04-2.03), with higher odds of self-injurious behavior (OR, 3.38; 95% CI, 2.54-4.50) and suicidality (OR, 3.84; 95% CI, 2.78-5.30), compared with children (OR, 2.99; 95% CI, 1.93-4.64 for self-injurious behavior, and OR, 2.53; 95% CI, 1.70-3.76 for suicidality).
 

Lightbulb moment?

Commenting for this news organization, Brenna Maddox, PhD, assistant professor of psychiatry at UNC Chapel Hill and co-chair of the American Association of Suicidology’s Autism and Suicide Committee, said “the sad reality” is that these findings won’t be surprising to many who work in the field.

“But for some clinicians and the public, this will be a lightbulb kind of moment, increasing awareness about a problem many of us have been talking about for a while,” said Dr. Maddox, who was not involved with the current research.

In January, she launched a 5-year, $9 million study to compare the efficacy of two suicide intervention programs in adolescents and young adults with autism.

The interventions use a well-known suicide prevention tool that has been newly modified for use in people with autism. One program would rely on the intervention alone, and the other would add a structured clinical follow-up.

“There has to be much more than awareness. We need more training for clinicians, we need more tools, we need to know which tools are going to work,” Dr. Maddox said.

Her new project could address all of those needs. Funded by the nonprofit Patient-Centered Outcomes Research Institute (PCORI), it will train 150 clinicians at centers in four states to identify suicidal risk among young adults with autism, utilize the prevention tool, and collect data on its efficacy alone or with follow-up.

Clinician training will begin this spring, and researchers hope to have the first patient data in the fall.
 

Scaling the ‘services cliff’

While Dr. Maddox’s study could yield a potential suicide prevention tool, she is quick to point out that the ultimate goal would be to have fewer people reach the point where such a tool is needed. However, that will take a multidisciplinary approach that begins with access to clinical care, including mental health care, she noted.

“Our mental health care system in general is not great for people on the spectrum, but it’s even worse for adults,” Dr. Maddox said.

Compared with neurotypical adults, adults with autism use more mental health services, have higher hospitalization rates, and are more likely to use primary care services, one recent study showed. The problem, Dr. Maddox notes, is that there are too few clinicians in those areas who are trained in autism care.

One way to address that issue is to mandate autism instruction in the medical curriculum, Catherine Lord, PhD, told this news organization when asked for comment. Dr. Lord is cochair of The Lancet commission on the future of care and clinical research in autism and professor of psychiatry at the Semel Institute for Neuroscience and Human Behavior at UCLA.

“Medical schools offer very little training on ASD, even in standard psychiatry training. For people who don’t specialize in child or adolescence psychiatry, there’s almost none,” Dr. Lord said.

Dr. Maddox agrees. One goal of the PCORI study is to turn their findings into a transportable training program, perhaps available via a webinar for clinicians, crisis center staff, and others who may encounter an adult with autism who is contemplating suicide.

“This is a life and death situation,” Dr. Maddox said. “We have to marshal every resource we have, and we have to do it now. We can’t waste time.”

Dr. Li’s study was funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development of the National Institutes of Health. Study authors and other sources reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

LAS VEGAS – In the opinion of Christoph U. Correll, MD, tardive dyskinesia (TD) “has been somewhat forgotten” by psychiatrists because the risk of patients developing the condition is considered to be significantly lower with second-generation antipsychotics compared with first-generation antipsychotics.

“But this does not seem to always be the case, because there is still a risk of TD, and we need to monitor for it,” Dr. Correll, professor of psychiatry and molecular medicine at The Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, New York, said during an annual psychopharmacology update held by the Nevada Psychiatric Association. “It is important to minimize the risk of TD by educating patients and caregivers about the risks of and alternatives to antipsychotic medication and early signs of TD.”

First described in 1957, TD is characterized by involuntary repetitive but irregular movements, mostly in the oral, lingual, and buccal regions – such as tongue protruding, puckering, chewing, and grimacing. Less often, there are movements in the hands, legs, feet, and torso. Symptoms can include mannerisms, stereotypies, tics, myoclonus, dystonias, tremor, and akathisia. “TD can be severe, persistent, and have medical and psychosocial consequences,” Dr. Correll said. “It can occur in untreated patients, but treatment with dopamine blocking agents – antipsychotics and metoclopramide – increases risk for TD.”

Differential diagnoses to consider include morbus Huntington, benign familial Chorea, and Sydenham’s Chorea. Less frequent causes of TD include metabolic conditions such as uremia, hyponatremia, hypernatremia, hypoparathyroidism, and hyperparathyroidism. “Those would need to be ruled out during the physical exam,” he said. There can also be inflammatory causes of TD such as herpes simplex virus, varicella, measles, mumps, and rubella.

A standard measure for TD diagnosis is the Abnormal Involuntary Movement Scale (AIMS), an observer-rated 12-item anchored scale that takes 5-10 minutes to administer. However, the AIMS on its own does not diagnose TD. In 1982, researchers developed three diagnostic criteria for TD: At least 3 months of cumulative antipsychotic drug exposure; presence of at least moderate abnormal involuntary movements in one or more body area(s) or mild movements in two or more body areas, and absence of other conditions that might produce involuntary movements (Arch Gen Psychiatry 1982;39:486-7).

The impact of TD on everyday functioning depends on anatomic location as well as severity, Dr. Correll continued. The condition can cause impairments to speech, verbal communication, dentition, temporomandibular joint pain/myalgia, swallowing difficulties, and fine motor skills including instrumental activities of daily living and written communication. Truncal and lower extremity TD can affect gait, posture and postural stability, strength, power flexibility, physical capacity, and one’s ability to exercise. “There are also psychological impairments,” he said. “Patients can develop different awareness so they become self-conscious; there can be cognitive abnormalities, and they can become more anxious or [have an] increased sense of paranoia, isolation, stigma, social and/or educational/vocational impairment.”

According to research by Dr. Correll and colleagues, unmodifiable patient-related risk factors for TD include older age, female sex, and being of white or African descent (J Neurol Sci 2018 June 15; 389:21-7). Unmodifiable illness-related risk factors include longer duration of illness, intellectual disability and brain damage, negative symptoms in schizophrenia, mood disorders, cognitive symptoms in mood disorders, and gene polymorphisms involving antipsychotic metabolism and dopamine functioning. Modifiable comorbidity-related factors include diabetes, smoking, and alcohol/substance abuse, while modifiable treatment-related factors include dopamine receptor blockers, higher cumulative and current antipsychotic dose or plasma levels, early parkinsonian side effects, treatment-emergent akathisia, and anticholinergic co-treatment. In a meta-analysis of 41 studies that aimed to determine the prevalence of TD, the mean age of the 11,493 patients was 43, 66% were male, and 77% had schizophrenia spectrum disorders (J Clin Psychiatry. 2017 Mar;78[3]:e264-78). The global mean TD prevalence was 25%, but the rates were lower with patients on current treatment with second-generation antipsychotics compared with those on first-generation antipsychotics (21% vs. 30%, respectively).

According to Dr. Correll, strategies for preventing TD include confirming and documenting the indication for dopamine antagonist antipsychotic medications, using conservative maintenance doses, and considering the use of SGAs, especially in those at high risk for EPS (extrapyramidal symptoms). “Don’t go too high [with the dose],” he said. “Stay below the EPS threshold. Inform patients and caregivers of the risk of TD and assess for incipient signs regularly using the AIMS.”

Treatment options include discontinuing antipsychotics, adjusting their dose, or switching patients from a first-generation antipsychotic to a second-generation antipsychotic. Supplementation with antioxidants/radical scavengers such as vitamin E, vitamin B₆, ginkgo biloba, and fish oil “can be tried, but have limited evidence, as is the case for melatonin.” Other options include clonazepam, amantadine, donepezil, and tetrabenazine, a reversible and specific inhibitor of vesicular monoamine transporter-2 (VMAT-2), a transporter that packages neurotransmitters (preferentially dopamine) into vesicles for release into the synapse and was approved in 2008 as an orphan drug for the treatment of choreiform movements associated with Huntington’s disease. “Neurologists have using tetrabenazine off-label for TD, but in schizophrenia and other psychiatric care, we rarely use it because it has to be given three times a day and it has a black box warning for depression and suicidality,” he said.

Dr. Correll noted that the Food and Drug Administration approval of two more recent VMAT-2 inhibitors – deutetrabenazine (Austedo) and valbenazine (Ingrezza) – provides an evidence-based care option for the effective management of TD. Deutetrabenazine requires titration over several weeks and twice-daily dosing, while valbenazine can reach the maximum dose by the beginning of week 2 and is dosed once daily. Deutetrabenazine should be taken with food, which is not required valbenazine.

“Both VMAT-2 inhibitors are generally well tolerated and have a positive benefit-risk ratio,” he said. “Both are recommended by the APA guidelines as the preferred and only evidence-based treatment for TD.”

Dr. Correll reported that he has received honoraria from and has been an advisory board member for numerous pharmaceutical companies. He has also received grant support from Janssen, the National Institute of Mental Health, the Patient Centered Outcomes Research Institute, Takeda, and the Thrasher Foundation.

LAS VEGAS – In the opinion of Christoph U. Correll, MD, tardive dyskinesia (TD) “has been somewhat forgotten” by psychiatrists because the risk of patients developing the condition is considered to be significantly lower with second-generation antipsychotics compared with first-generation antipsychotics.

“But this does not seem to always be the case, because there is still a risk of TD, and we need to monitor for it,” Dr. Correll, professor of psychiatry and molecular medicine at The Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, New York, said during an annual psychopharmacology update held by the Nevada Psychiatric Association. “It is important to minimize the risk of TD by educating patients and caregivers about the risks of and alternatives to antipsychotic medication and early signs of TD.”

First described in 1957, TD is characterized by involuntary repetitive but irregular movements, mostly in the oral, lingual, and buccal regions – such as tongue protruding, puckering, chewing, and grimacing. Less often, there are movements in the hands, legs, feet, and torso. Symptoms can include mannerisms, stereotypies, tics, myoclonus, dystonias, tremor, and akathisia. “TD can be severe, persistent, and have medical and psychosocial consequences,” Dr. Correll said. “It can occur in untreated patients, but treatment with dopamine blocking agents – antipsychotics and metoclopramide – increases risk for TD.”

Differential diagnoses to consider include morbus Huntington, benign familial Chorea, and Sydenham’s Chorea. Less frequent causes of TD include metabolic conditions such as uremia, hyponatremia, hypernatremia, hypoparathyroidism, and hyperparathyroidism. “Those would need to be ruled out during the physical exam,” he said. There can also be inflammatory causes of TD such as herpes simplex virus, varicella, measles, mumps, and rubella.

A standard measure for TD diagnosis is the Abnormal Involuntary Movement Scale (AIMS), an observer-rated 12-item anchored scale that takes 5-10 minutes to administer. However, the AIMS on its own does not diagnose TD. In 1982, researchers developed three diagnostic criteria for TD: At least 3 months of cumulative antipsychotic drug exposure; presence of at least moderate abnormal involuntary movements in one or more body area(s) or mild movements in two or more body areas, and absence of other conditions that might produce involuntary movements (Arch Gen Psychiatry 1982;39:486-7).

The impact of TD on everyday functioning depends on anatomic location as well as severity, Dr. Correll continued. The condition can cause impairments to speech, verbal communication, dentition, temporomandibular joint pain/myalgia, swallowing difficulties, and fine motor skills including instrumental activities of daily living and written communication. Truncal and lower extremity TD can affect gait, posture and postural stability, strength, power flexibility, physical capacity, and one’s ability to exercise. “There are also psychological impairments,” he said. “Patients can develop different awareness so they become self-conscious; there can be cognitive abnormalities, and they can become more anxious or [have an] increased sense of paranoia, isolation, stigma, social and/or educational/vocational impairment.”

According to research by Dr. Correll and colleagues, unmodifiable patient-related risk factors for TD include older age, female sex, and being of white or African descent (J Neurol Sci 2018 June 15; 389:21-7). Unmodifiable illness-related risk factors include longer duration of illness, intellectual disability and brain damage, negative symptoms in schizophrenia, mood disorders, cognitive symptoms in mood disorders, and gene polymorphisms involving antipsychotic metabolism and dopamine functioning. Modifiable comorbidity-related factors include diabetes, smoking, and alcohol/substance abuse, while modifiable treatment-related factors include dopamine receptor blockers, higher cumulative and current antipsychotic dose or plasma levels, early parkinsonian side effects, treatment-emergent akathisia, and anticholinergic co-treatment. In a meta-analysis of 41 studies that aimed to determine the prevalence of TD, the mean age of the 11,493 patients was 43, 66% were male, and 77% had schizophrenia spectrum disorders (J Clin Psychiatry. 2017 Mar;78[3]:e264-78). The global mean TD prevalence was 25%, but the rates were lower with patients on current treatment with second-generation antipsychotics compared with those on first-generation antipsychotics (21% vs. 30%, respectively).

According to Dr. Correll, strategies for preventing TD include confirming and documenting the indication for dopamine antagonist antipsychotic medications, using conservative maintenance doses, and considering the use of SGAs, especially in those at high risk for EPS (extrapyramidal symptoms). “Don’t go too high [with the dose],” he said. “Stay below the EPS threshold. Inform patients and caregivers of the risk of TD and assess for incipient signs regularly using the AIMS.”

Treatment options include discontinuing antipsychotics, adjusting their dose, or switching patients from a first-generation antipsychotic to a second-generation antipsychotic. Supplementation with antioxidants/radical scavengers such as vitamin E, vitamin B₆, ginkgo biloba, and fish oil “can be tried, but have limited evidence, as is the case for melatonin.” Other options include clonazepam, amantadine, donepezil, and tetrabenazine, a reversible and specific inhibitor of vesicular monoamine transporter-2 (VMAT-2), a transporter that packages neurotransmitters (preferentially dopamine) into vesicles for release into the synapse and was approved in 2008 as an orphan drug for the treatment of choreiform movements associated with Huntington’s disease. “Neurologists have using tetrabenazine off-label for TD, but in schizophrenia and other psychiatric care, we rarely use it because it has to be given three times a day and it has a black box warning for depression and suicidality,” he said.

Dr. Correll noted that the Food and Drug Administration approval of two more recent VMAT-2 inhibitors – deutetrabenazine (Austedo) and valbenazine (Ingrezza) – provides an evidence-based care option for the effective management of TD. Deutetrabenazine requires titration over several weeks and twice-daily dosing, while valbenazine can reach the maximum dose by the beginning of week 2 and is dosed once daily. Deutetrabenazine should be taken with food, which is not required valbenazine.

“Both VMAT-2 inhibitors are generally well tolerated and have a positive benefit-risk ratio,” he said. “Both are recommended by the APA guidelines as the preferred and only evidence-based treatment for TD.”

Dr. Correll reported that he has received honoraria from and has been an advisory board member for numerous pharmaceutical companies. He has also received grant support from Janssen, the National Institute of Mental Health, the Patient Centered Outcomes Research Institute, Takeda, and the Thrasher Foundation.

LAS VEGAS – In the opinion of Christoph U. Correll, MD, tardive dyskinesia (TD) “has been somewhat forgotten” by psychiatrists because the risk of patients developing the condition is considered to be significantly lower with second-generation antipsychotics compared with first-generation antipsychotics.

“But this does not seem to always be the case, because there is still a risk of TD, and we need to monitor for it,” Dr. Correll, professor of psychiatry and molecular medicine at The Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, New York, said during an annual psychopharmacology update held by the Nevada Psychiatric Association. “It is important to minimize the risk of TD by educating patients and caregivers about the risks of and alternatives to antipsychotic medication and early signs of TD.”

First described in 1957, TD is characterized by involuntary repetitive but irregular movements, mostly in the oral, lingual, and buccal regions – such as tongue protruding, puckering, chewing, and grimacing. Less often, there are movements in the hands, legs, feet, and torso. Symptoms can include mannerisms, stereotypies, tics, myoclonus, dystonias, tremor, and akathisia. “TD can be severe, persistent, and have medical and psychosocial consequences,” Dr. Correll said. “It can occur in untreated patients, but treatment with dopamine blocking agents – antipsychotics and metoclopramide – increases risk for TD.”

Differential diagnoses to consider include morbus Huntington, benign familial Chorea, and Sydenham’s Chorea. Less frequent causes of TD include metabolic conditions such as uremia, hyponatremia, hypernatremia, hypoparathyroidism, and hyperparathyroidism. “Those would need to be ruled out during the physical exam,” he said. There can also be inflammatory causes of TD such as herpes simplex virus, varicella, measles, mumps, and rubella.

A standard measure for TD diagnosis is the Abnormal Involuntary Movement Scale (AIMS), an observer-rated 12-item anchored scale that takes 5-10 minutes to administer. However, the AIMS on its own does not diagnose TD. In 1982, researchers developed three diagnostic criteria for TD: At least 3 months of cumulative antipsychotic drug exposure; presence of at least moderate abnormal involuntary movements in one or more body area(s) or mild movements in two or more body areas, and absence of other conditions that might produce involuntary movements (Arch Gen Psychiatry 1982;39:486-7).

The impact of TD on everyday functioning depends on anatomic location as well as severity, Dr. Correll continued. The condition can cause impairments to speech, verbal communication, dentition, temporomandibular joint pain/myalgia, swallowing difficulties, and fine motor skills including instrumental activities of daily living and written communication. Truncal and lower extremity TD can affect gait, posture and postural stability, strength, power flexibility, physical capacity, and one’s ability to exercise. “There are also psychological impairments,” he said. “Patients can develop different awareness so they become self-conscious; there can be cognitive abnormalities, and they can become more anxious or [have an] increased sense of paranoia, isolation, stigma, social and/or educational/vocational impairment.”

According to research by Dr. Correll and colleagues, unmodifiable patient-related risk factors for TD include older age, female sex, and being of white or African descent (J Neurol Sci 2018 June 15; 389:21-7). Unmodifiable illness-related risk factors include longer duration of illness, intellectual disability and brain damage, negative symptoms in schizophrenia, mood disorders, cognitive symptoms in mood disorders, and gene polymorphisms involving antipsychotic metabolism and dopamine functioning. Modifiable comorbidity-related factors include diabetes, smoking, and alcohol/substance abuse, while modifiable treatment-related factors include dopamine receptor blockers, higher cumulative and current antipsychotic dose or plasma levels, early parkinsonian side effects, treatment-emergent akathisia, and anticholinergic co-treatment. In a meta-analysis of 41 studies that aimed to determine the prevalence of TD, the mean age of the 11,493 patients was 43, 66% were male, and 77% had schizophrenia spectrum disorders (J Clin Psychiatry. 2017 Mar;78[3]:e264-78). The global mean TD prevalence was 25%, but the rates were lower with patients on current treatment with second-generation antipsychotics compared with those on first-generation antipsychotics (21% vs. 30%, respectively).

According to Dr. Correll, strategies for preventing TD include confirming and documenting the indication for dopamine antagonist antipsychotic medications, using conservative maintenance doses, and considering the use of SGAs, especially in those at high risk for EPS (extrapyramidal symptoms). “Don’t go too high [with the dose],” he said. “Stay below the EPS threshold. Inform patients and caregivers of the risk of TD and assess for incipient signs regularly using the AIMS.”

Treatment options include discontinuing antipsychotics, adjusting their dose, or switching patients from a first-generation antipsychotic to a second-generation antipsychotic. Supplementation with antioxidants/radical scavengers such as vitamin E, vitamin B₆, ginkgo biloba, and fish oil “can be tried, but have limited evidence, as is the case for melatonin.” Other options include clonazepam, amantadine, donepezil, and tetrabenazine, a reversible and specific inhibitor of vesicular monoamine transporter-2 (VMAT-2), a transporter that packages neurotransmitters (preferentially dopamine) into vesicles for release into the synapse and was approved in 2008 as an orphan drug for the treatment of choreiform movements associated with Huntington’s disease. “Neurologists have using tetrabenazine off-label for TD, but in schizophrenia and other psychiatric care, we rarely use it because it has to be given three times a day and it has a black box warning for depression and suicidality,” he said.

Dr. Correll noted that the Food and Drug Administration approval of two more recent VMAT-2 inhibitors – deutetrabenazine (Austedo) and valbenazine (Ingrezza) – provides an evidence-based care option for the effective management of TD. Deutetrabenazine requires titration over several weeks and twice-daily dosing, while valbenazine can reach the maximum dose by the beginning of week 2 and is dosed once daily. Deutetrabenazine should be taken with food, which is not required valbenazine.

“Both VMAT-2 inhibitors are generally well tolerated and have a positive benefit-risk ratio,” he said. “Both are recommended by the APA guidelines as the preferred and only evidence-based treatment for TD.”

Dr. Correll reported that he has received honoraria from and has been an advisory board member for numerous pharmaceutical companies. He has also received grant support from Janssen, the National Institute of Mental Health, the Patient Centered Outcomes Research Institute, Takeda, and the Thrasher Foundation.

Childhood-onset insomnia is a chronic problem in 43% of children, based on 15-year follow-up data from approximately 500 individuals.

Difficulty initiating or maintaining sleep (DIMS) is the most frequently reported insomnia symptom in children and teens, but longitudinal data on the trajectory of insomnia symptoms from childhood into adulthood are limited, Julio Fernandez-Mendoza, PhD, of Penn State University, Hershey, and colleagues wrote.

Previous studies have shown varying results, notably on the effect of objective short sleep duration (OSSD), they said. The extent to which the effect of OSSD on insomnia trajectories, and whether OSSD affects the development of insomnia in the transition to adulthood remains uncertain.

In a study published in Pediatrics, the researchers reviewed data from 502 children who enrolled at age 5-12 years between 2000 and 2005. The participants underwent laboratory polysomnography visits at baseline; 421 had a second laboratory visit between 2010 and 2013 (median age, 16 years), and 502 completed a structured self-reported survey between 2018 and 2021 at a median age of 24 years. At the first visit, 118 children met criteria for insomnia, defined as parent reports of often/moderate or very often/severe DIMS and/or use of over-the-counter or prescription sleep medications for DIMS. At the second visit, 120 children met the definition for insomnia.

Among children with insomnia symptoms at baseline, 53.7% had persistence of insomnia symptoms in adolescence and 61.9% had symptoms in young adulthood; 46.3% and 38.1% remitted at these times.

Among children with insomnia symptoms at adolescence, 57.5% and 42.5% had persistence and remittance, respectively, in young adulthood.

In children with insomnia at baseline, therefore, the most frequent developmental trajectory was persistence (43.3%) followed by remission (26.9% since childhood and 11.2% since adolescence) and a waxing and waning pattern (18.6%), the researchers said.

Among children with normal sleep at baseline, 69.7% retained normal sleep patterns in adolescence and 63.3% retained normal sleep in young adulthood; 30.3% and 36.7% developed insomnia in adolescence and young adulthood, respectively.

Overall, adult insomnia was reported by 22.0% and 20.8% of individuals with childhood and adolescent insomnia, respectively. In a multivariate analysis, the odds of adult insomnia were 2.6 times and 5.5 times higher among those with histories of short-sleeping in childhood and adolescence, respectively.

“The most common developmental trajectory for insomnia symptoms was that of persistence from childhood through young adulthood,” the researchers wrote in their discussion of the study.

“These 15-year longitudinal findings across three developmental stages indicate that insomnia symptoms should not be expected to developmentally remit in at least 40% of children and that adolescence is a critical developmental period for the adverse prognosis of the insomnia with short sleep duration phenotype,” they emphasized.

The study findings were limited by several factors including the collection of OSSD and other sleep data via a 1-night, 9-hour polysomnography, which might not be representative of habitual sleep at home, the researchers noted. Other limitations include the lack of polysomnography data to accompany the young adult survey and the inability to validate insomnia in young adults via strict diagnostic criteria.

However, the results reveal that the persistence of childhood insomnia is higher than suggested in previous studies, and that these children and adolescents, especially short sleepers, are at significantly increased risk of adult insomnia, the researchers concluded.

“Early sleep interventions are a priority, as clinicians should not expect insomnia symptoms to developmentally remit in a high proportion of children, although objective sleep measures may be indicated in adolescence to identify those with poorer long-term prognosis,” they said.

Pandemic prompts interest in sleep issues

The current study is important at this time because sleep disruptions in children and adolescents have increased over the course of the COVID-19 pandemic, Karalyn Kinsella, MD, a pediatrician in private practice in Cheshire, Conn., said in an interview.

Dr. Kinsella said she was especially surprised to see that adolescent insomnia will most likely not remit in young adulthood, as she had considered it a disorder of adolescence.

The study highlights the need for early intervention to manage insomnia in children. However, there are several barriers to such intervention. “Parents [of young children] are overwhelmed and just need sleep themselves, so they don’t always have the energy to work on good sleep habits in their children,” she said. Improving sleep habits in adolescents requires overcoming the barrier of the young patients’ attitudes. “For adolescents, they need to buy into the change.”

However, the take-home message for clinicians is that it is important to work to overcome these barriers and improve sleep in children and teens, because the longitudinal data suggest that the problem is “likely to persist and unlikely to remit,” for many, she said.

As for additional studies, “I would like to see more research done on neurologic and psychological causes of insomnia,” Dr. Kinsella said.

The study was supported in part by grants from the National Heart, Lung, and Blood Institute; National Institute of Mental Health; and the National Center for Advancing Translational Sciences of the National Institutes of Health. The researchers had no financial conflicts to disclose. Dr. Kinsella had no financial conflicts to disclose and serves on the editorial advisory board of Pediatric News.

Childhood-onset insomnia is a chronic problem in 43% of children, based on 15-year follow-up data from approximately 500 individuals.

Difficulty initiating or maintaining sleep (DIMS) is the most frequently reported insomnia symptom in children and teens, but longitudinal data on the trajectory of insomnia symptoms from childhood into adulthood are limited, Julio Fernandez-Mendoza, PhD, of Penn State University, Hershey, and colleagues wrote.

Previous studies have shown varying results, notably on the effect of objective short sleep duration (OSSD), they said. The extent to which the effect of OSSD on insomnia trajectories, and whether OSSD affects the development of insomnia in the transition to adulthood remains uncertain.

In a study published in Pediatrics, the researchers reviewed data from 502 children who enrolled at age 5-12 years between 2000 and 2005. The participants underwent laboratory polysomnography visits at baseline; 421 had a second laboratory visit between 2010 and 2013 (median age, 16 years), and 502 completed a structured self-reported survey between 2018 and 2021 at a median age of 24 years. At the first visit, 118 children met criteria for insomnia, defined as parent reports of often/moderate or very often/severe DIMS and/or use of over-the-counter or prescription sleep medications for DIMS. At the second visit, 120 children met the definition for insomnia.

Among children with insomnia symptoms at baseline, 53.7% had persistence of insomnia symptoms in adolescence and 61.9% had symptoms in young adulthood; 46.3% and 38.1% remitted at these times.

Among children with insomnia symptoms at adolescence, 57.5% and 42.5% had persistence and remittance, respectively, in young adulthood.

In children with insomnia at baseline, therefore, the most frequent developmental trajectory was persistence (43.3%) followed by remission (26.9% since childhood and 11.2% since adolescence) and a waxing and waning pattern (18.6%), the researchers said.

Among children with normal sleep at baseline, 69.7% retained normal sleep patterns in adolescence and 63.3% retained normal sleep in young adulthood; 30.3% and 36.7% developed insomnia in adolescence and young adulthood, respectively.

Overall, adult insomnia was reported by 22.0% and 20.8% of individuals with childhood and adolescent insomnia, respectively. In a multivariate analysis, the odds of adult insomnia were 2.6 times and 5.5 times higher among those with histories of short-sleeping in childhood and adolescence, respectively.

“The most common developmental trajectory for insomnia symptoms was that of persistence from childhood through young adulthood,” the researchers wrote in their discussion of the study.

“These 15-year longitudinal findings across three developmental stages indicate that insomnia symptoms should not be expected to developmentally remit in at least 40% of children and that adolescence is a critical developmental period for the adverse prognosis of the insomnia with short sleep duration phenotype,” they emphasized.

The study findings were limited by several factors including the collection of OSSD and other sleep data via a 1-night, 9-hour polysomnography, which might not be representative of habitual sleep at home, the researchers noted. Other limitations include the lack of polysomnography data to accompany the young adult survey and the inability to validate insomnia in young adults via strict diagnostic criteria.

However, the results reveal that the persistence of childhood insomnia is higher than suggested in previous studies, and that these children and adolescents, especially short sleepers, are at significantly increased risk of adult insomnia, the researchers concluded.

“Early sleep interventions are a priority, as clinicians should not expect insomnia symptoms to developmentally remit in a high proportion of children, although objective sleep measures may be indicated in adolescence to identify those with poorer long-term prognosis,” they said.

Pandemic prompts interest in sleep issues

The current study is important at this time because sleep disruptions in children and adolescents have increased over the course of the COVID-19 pandemic, Karalyn Kinsella, MD, a pediatrician in private practice in Cheshire, Conn., said in an interview.

Dr. Kinsella said she was especially surprised to see that adolescent insomnia will most likely not remit in young adulthood, as she had considered it a disorder of adolescence.

The study highlights the need for early intervention to manage insomnia in children. However, there are several barriers to such intervention. “Parents [of young children] are overwhelmed and just need sleep themselves, so they don’t always have the energy to work on good sleep habits in their children,” she said. Improving sleep habits in adolescents requires overcoming the barrier of the young patients’ attitudes. “For adolescents, they need to buy into the change.”

However, the take-home message for clinicians is that it is important to work to overcome these barriers and improve sleep in children and teens, because the longitudinal data suggest that the problem is “likely to persist and unlikely to remit,” for many, she said.

As for additional studies, “I would like to see more research done on neurologic and psychological causes of insomnia,” Dr. Kinsella said.

The study was supported in part by grants from the National Heart, Lung, and Blood Institute; National Institute of Mental Health; and the National Center for Advancing Translational Sciences of the National Institutes of Health. The researchers had no financial conflicts to disclose. Dr. Kinsella had no financial conflicts to disclose and serves on the editorial advisory board of Pediatric News.

Childhood-onset insomnia is a chronic problem in 43% of children, based on 15-year follow-up data from approximately 500 individuals.

Difficulty initiating or maintaining sleep (DIMS) is the most frequently reported insomnia symptom in children and teens, but longitudinal data on the trajectory of insomnia symptoms from childhood into adulthood are limited, Julio Fernandez-Mendoza, PhD, of Penn State University, Hershey, and colleagues wrote.

Previous studies have shown varying results, notably on the effect of objective short sleep duration (OSSD), they said. The extent to which the effect of OSSD on insomnia trajectories, and whether OSSD affects the development of insomnia in the transition to adulthood remains uncertain.

In a study published in Pediatrics, the researchers reviewed data from 502 children who enrolled at age 5-12 years between 2000 and 2005. The participants underwent laboratory polysomnography visits at baseline; 421 had a second laboratory visit between 2010 and 2013 (median age, 16 years), and 502 completed a structured self-reported survey between 2018 and 2021 at a median age of 24 years. At the first visit, 118 children met criteria for insomnia, defined as parent reports of often/moderate or very often/severe DIMS and/or use of over-the-counter or prescription sleep medications for DIMS. At the second visit, 120 children met the definition for insomnia.

Among children with insomnia symptoms at baseline, 53.7% had persistence of insomnia symptoms in adolescence and 61.9% had symptoms in young adulthood; 46.3% and 38.1% remitted at these times.

Among children with insomnia symptoms at adolescence, 57.5% and 42.5% had persistence and remittance, respectively, in young adulthood.

In children with insomnia at baseline, therefore, the most frequent developmental trajectory was persistence (43.3%) followed by remission (26.9% since childhood and 11.2% since adolescence) and a waxing and waning pattern (18.6%), the researchers said.

Among children with normal sleep at baseline, 69.7% retained normal sleep patterns in adolescence and 63.3% retained normal sleep in young adulthood; 30.3% and 36.7% developed insomnia in adolescence and young adulthood, respectively.

Overall, adult insomnia was reported by 22.0% and 20.8% of individuals with childhood and adolescent insomnia, respectively. In a multivariate analysis, the odds of adult insomnia were 2.6 times and 5.5 times higher among those with histories of short-sleeping in childhood and adolescence, respectively.

“The most common developmental trajectory for insomnia symptoms was that of persistence from childhood through young adulthood,” the researchers wrote in their discussion of the study.

“These 15-year longitudinal findings across three developmental stages indicate that insomnia symptoms should not be expected to developmentally remit in at least 40% of children and that adolescence is a critical developmental period for the adverse prognosis of the insomnia with short sleep duration phenotype,” they emphasized.

The study findings were limited by several factors including the collection of OSSD and other sleep data via a 1-night, 9-hour polysomnography, which might not be representative of habitual sleep at home, the researchers noted. Other limitations include the lack of polysomnography data to accompany the young adult survey and the inability to validate insomnia in young adults via strict diagnostic criteria.

However, the results reveal that the persistence of childhood insomnia is higher than suggested in previous studies, and that these children and adolescents, especially short sleepers, are at significantly increased risk of adult insomnia, the researchers concluded.

“Early sleep interventions are a priority, as clinicians should not expect insomnia symptoms to developmentally remit in a high proportion of children, although objective sleep measures may be indicated in adolescence to identify those with poorer long-term prognosis,” they said.

Pandemic prompts interest in sleep issues

The current study is important at this time because sleep disruptions in children and adolescents have increased over the course of the COVID-19 pandemic, Karalyn Kinsella, MD, a pediatrician in private practice in Cheshire, Conn., said in an interview.

Dr. Kinsella said she was especially surprised to see that adolescent insomnia will most likely not remit in young adulthood, as she had considered it a disorder of adolescence.

The study highlights the need for early intervention to manage insomnia in children. However, there are several barriers to such intervention. “Parents [of young children] are overwhelmed and just need sleep themselves, so they don’t always have the energy to work on good sleep habits in their children,” she said. Improving sleep habits in adolescents requires overcoming the barrier of the young patients’ attitudes. “For adolescents, they need to buy into the change.”

However, the take-home message for clinicians is that it is important to work to overcome these barriers and improve sleep in children and teens, because the longitudinal data suggest that the problem is “likely to persist and unlikely to remit,” for many, she said.

As for additional studies, “I would like to see more research done on neurologic and psychological causes of insomnia,” Dr. Kinsella said.

The study was supported in part by grants from the National Heart, Lung, and Blood Institute; National Institute of Mental Health; and the National Center for Advancing Translational Sciences of the National Institutes of Health. The researchers had no financial conflicts to disclose. Dr. Kinsella had no financial conflicts to disclose and serves on the editorial advisory board of Pediatric News.

Engaging with a “chatbot,” a computer program that simulates human conversation, helps prevent eating disorders (EDs) in at-risk individuals, new research suggests.

Results of a randomized trial show that at-risk women who interacted with the chatbot showed lower concern about their weight and body shape compared to a wait-list control group.

“Chatbots are widely used in industry and have begun to be used in medical settings, although few studies have examined their effectiveness for mental health issues and none address EDs or ED prevention,” senior investigator C. Barr Taylor, MD, a research faculty member at Palo Alto (Calif.) University, said in a press release.

“We found that the group with access to the chatbot had a greater reduction in weight and shape concerns, both right after using it at 3 months and at the 6-month follow-up. The effects had sustainability over time, and we also found indication that the chatbot may reduce ED onset more so than the control group, where there was a greater incidence of EDs,” Dr. Taylor told this news organization.

The study was published online Dec. 28, 2021, in the International Journal of Eating Disorders.
 

Deadly disorders

“EDs are a common problem with huge risk factors; and, given how widespread they are, we need scalable tools that can reach a lot of people at low cost, reduce risk factors for developing an ED – which is the second most deadly of all psychiatric illnesses – so prevention is of the utmost importance,” Dr. Taylor said.

The investigators developed a targeted Internet-based preventive program called StudentBodies that utilizes cognitive-behavioral therapy approaches. The program was successful in reducing weight/shape concerns in women at high risk for the onset of an ED, and it reduced ED onset in the highest-risk women.

However, it required trained moderators who spent over 45 minutes with participants. Given the large number of people at risk for an ED who might benefit, the researchers noted that it is unlikely that a human-moderated version would be widely disseminated.

A chatbot may represent a “possible solution to reducing delivery costs” because it mimics aspects of human moderation in simulating conversations, the investigators noted.

“We wanted to take the earlier program we developed into this century and program it for delivery in this new format that would allow for bite-size pieces of information for the chatbot to communicate to the user,” lead author Ellen Fitzsimmons-Craft, PhD, assistant professor of psychiatry, Washington University, St. Louis, told this news organization.

“Our ED prevention online version was more effective when there was guidance from a human moderator who could provide feedback on progress, encourage you to go on, and apply the skills in daily life. But that’s not the most scalable. So we thought that a chatbot, in addition to providing content in this perhaps more engaging format, could also provide some aspect of human moderation, although the person is chatting with a robot,” added Dr. Fitzsimmons-Craft, associate director of the Center for Healthy Weight and Wellness.
 

Tessa will speak to you now

Participants (n = 700 women; mean [SD] age, 21.08 [3.09] years; 84.6% White; 53.8% heterosexual; 31.08% bisexual), were randomized to an intervention group or a wait-list control group (n = 352 and 348, respectively). There were no significant differences between groups in age, race, ethnicity, education, or sexual orientation.

The StudentBodies program was adapted for delivery via a chatbot named Tessa “while retaining the core intervention principles” and referred to as “Body Positive.”

It consisted of several components programmed into the chatbot, which initiated each conversation in a predetermined order. Participants were encouraged to engage in two conversations weekly. The program included an introduction and eight sessions as well as a crisis module that provided users with a referral to a crisis hotline in case of emergency. Referral was triggered on the basis of “recognized keywords,” such as “hurting myself.”

The researchers used the Weight Concerns Scale questionnaire to assess weight and shape concerns and the Internalization: Thin/Low Body Fat subscale of the Sociocultural Attitudes Toward Appearance Questionnaire–4 to “assess the cognitive aspect of thin-ideal internalization.”

Secondary outcomes tested the hypothesis that the chatbot would be more likely to reduce clinical outcomes (ED psychopathology, depression, and anxiety) and prevent ED onset, compared to the control condition.
 

Ready for prime time

At 3- and 6-month follow-up, there was significantly greater reduction in the intervention group compared with the control group in weight/shape concerns (d = -.20, P = .03 and d = -.19, P = .04, respectively), although there were no differences in thin-ideal internalization change.

The chatbot intervention was associated with significantly greater reductions in overall ED psychopathology at 3 months (d = -.29, P = .003) compared to the control condition, but not at 6 months.

Notably, the intervention group had significantly higher odds than the control group of remaining nonclinical for EDs at 3- and 6-month follow-up (OR, 2.37 [95% confidence interval, 1.37-4.11] and OR, 2.13 [95% CI,1.26-3.59], respectively).

“We were very excited about the study, and frankly, I was surprised by the effectiveness [of the chatbot intervention] because I didn’t think it would have as much of an impact as it did,” said Dr. Taylor. “Prevention gets short shrift everywhere, and I think we succeeded very well.”

Dr. Fitzsimmons-Craft added that the National Eating Disorders Association (NEDA) has agreed to make the chatbot available on its website for people who screen positive for having an ED or for being at high risk, and so their group is working with their industry partner, a company called X2AI, which developed the chatbot, to make this happen.

“This is definitely the fastest research-to-practice translation I’ve ever seen, where we can so quickly show that it works and make it available to tens of thousands almost immediately.”

Dr. Fitzsimmons-Craft is optimistic that it will be available to launch the week of Feb. 21, which is National Eating Disorders Week.
 

Innovative, creative research

Commenting on the research, Evelyn Attia, MD, professor of psychiatry, Columbia University Medical Center, and director of the Columbia Center for Eating Disorders New York–Presbyterian Hospital, New York, described the study as “innovative and creative.”

New York-Presbyterian Hospital

Dr. Attia, a member of the Research Advisory Council of the NEDA, noted that the structure of the study is “very preliminary” and that the comparison to a wait-list control makes it hard to know whether this is an effective intervention compared with other types of interventions, rather than compared with no intervention.

“But I’m sure that when the researchers are set up and primed to study this more robustly, they will consider a more active control intervention to see whether this preliminary finding holds up,” she said.

Also commenting on the study, Deborah R. Glasofer, PhD, associate professor of clinical medical psychology (in psychiatry), Columbia Center for Eating Disorders, said, “Higher-than-average concern about appearance – body shape, size, or weight – and a tightly held belief that it is ideal to be thin are known risk factors for the development of an eating disorder.

“This study offers an indication that technology can be leveraged to fill a gap and help folks before unhelpful and sometimes misguided thoughts about food, eating, and appearance evolve into a full-blown eating disorder,” said Dr. Glasofer, who was not involved with the study.

The study was supported by the NEDA Feeding Hope Fund, the National Institute of Mental Health, the National Heart, Lung, and Blood Institute, and the Swedish Research Council. The authors and Dr. Glasofer have disclosed no relevant financial relationships. Dr. Attia is on the board and the Research Advisory Council of NEDA.

A version of this article first appeared on Medscape.com.

Engaging with a “chatbot,” a computer program that simulates human conversation, helps prevent eating disorders (EDs) in at-risk individuals, new research suggests.

Results of a randomized trial show that at-risk women who interacted with the chatbot showed lower concern about their weight and body shape compared to a wait-list control group.

“Chatbots are widely used in industry and have begun to be used in medical settings, although few studies have examined their effectiveness for mental health issues and none address EDs or ED prevention,” senior investigator C. Barr Taylor, MD, a research faculty member at Palo Alto (Calif.) University, said in a press release.

“We found that the group with access to the chatbot had a greater reduction in weight and shape concerns, both right after using it at 3 months and at the 6-month follow-up. The effects had sustainability over time, and we also found indication that the chatbot may reduce ED onset more so than the control group, where there was a greater incidence of EDs,” Dr. Taylor told this news organization.

The study was published online Dec. 28, 2021, in the International Journal of Eating Disorders.
 

Deadly disorders

“EDs are a common problem with huge risk factors; and, given how widespread they are, we need scalable tools that can reach a lot of people at low cost, reduce risk factors for developing an ED – which is the second most deadly of all psychiatric illnesses – so prevention is of the utmost importance,” Dr. Taylor said.

The investigators developed a targeted Internet-based preventive program called StudentBodies that utilizes cognitive-behavioral therapy approaches. The program was successful in reducing weight/shape concerns in women at high risk for the onset of an ED, and it reduced ED onset in the highest-risk women.

However, it required trained moderators who spent over 45 minutes with participants. Given the large number of people at risk for an ED who might benefit, the researchers noted that it is unlikely that a human-moderated version would be widely disseminated.

A chatbot may represent a “possible solution to reducing delivery costs” because it mimics aspects of human moderation in simulating conversations, the investigators noted.

“We wanted to take the earlier program we developed into this century and program it for delivery in this new format that would allow for bite-size pieces of information for the chatbot to communicate to the user,” lead author Ellen Fitzsimmons-Craft, PhD, assistant professor of psychiatry, Washington University, St. Louis, told this news organization.

“Our ED prevention online version was more effective when there was guidance from a human moderator who could provide feedback on progress, encourage you to go on, and apply the skills in daily life. But that’s not the most scalable. So we thought that a chatbot, in addition to providing content in this perhaps more engaging format, could also provide some aspect of human moderation, although the person is chatting with a robot,” added Dr. Fitzsimmons-Craft, associate director of the Center for Healthy Weight and Wellness.
 

Tessa will speak to you now

Participants (n = 700 women; mean [SD] age, 21.08 [3.09] years; 84.6% White; 53.8% heterosexual; 31.08% bisexual), were randomized to an intervention group or a wait-list control group (n = 352 and 348, respectively). There were no significant differences between groups in age, race, ethnicity, education, or sexual orientation.

The StudentBodies program was adapted for delivery via a chatbot named Tessa “while retaining the core intervention principles” and referred to as “Body Positive.”

It consisted of several components programmed into the chatbot, which initiated each conversation in a predetermined order. Participants were encouraged to engage in two conversations weekly. The program included an introduction and eight sessions as well as a crisis module that provided users with a referral to a crisis hotline in case of emergency. Referral was triggered on the basis of “recognized keywords,” such as “hurting myself.”

The researchers used the Weight Concerns Scale questionnaire to assess weight and shape concerns and the Internalization: Thin/Low Body Fat subscale of the Sociocultural Attitudes Toward Appearance Questionnaire–4 to “assess the cognitive aspect of thin-ideal internalization.”

Secondary outcomes tested the hypothesis that the chatbot would be more likely to reduce clinical outcomes (ED psychopathology, depression, and anxiety) and prevent ED onset, compared to the control condition.
 

Ready for prime time

At 3- and 6-month follow-up, there was significantly greater reduction in the intervention group compared with the control group in weight/shape concerns (d = -.20, P = .03 and d = -.19, P = .04, respectively), although there were no differences in thin-ideal internalization change.

The chatbot intervention was associated with significantly greater reductions in overall ED psychopathology at 3 months (d = -.29, P = .003) compared to the control condition, but not at 6 months.

Notably, the intervention group had significantly higher odds than the control group of remaining nonclinical for EDs at 3- and 6-month follow-up (OR, 2.37 [95% confidence interval, 1.37-4.11] and OR, 2.13 [95% CI,1.26-3.59], respectively).

“We were very excited about the study, and frankly, I was surprised by the effectiveness [of the chatbot intervention] because I didn’t think it would have as much of an impact as it did,” said Dr. Taylor. “Prevention gets short shrift everywhere, and I think we succeeded very well.”

Dr. Fitzsimmons-Craft added that the National Eating Disorders Association (NEDA) has agreed to make the chatbot available on its website for people who screen positive for having an ED or for being at high risk, and so their group is working with their industry partner, a company called X2AI, which developed the chatbot, to make this happen.

“This is definitely the fastest research-to-practice translation I’ve ever seen, where we can so quickly show that it works and make it available to tens of thousands almost immediately.”

Dr. Fitzsimmons-Craft is optimistic that it will be available to launch the week of Feb. 21, which is National Eating Disorders Week.
 

Innovative, creative research

Commenting on the research, Evelyn Attia, MD, professor of psychiatry, Columbia University Medical Center, and director of the Columbia Center for Eating Disorders New York–Presbyterian Hospital, New York, described the study as “innovative and creative.”

New York-Presbyterian Hospital

Dr. Attia, a member of the Research Advisory Council of the NEDA, noted that the structure of the study is “very preliminary” and that the comparison to a wait-list control makes it hard to know whether this is an effective intervention compared with other types of interventions, rather than compared with no intervention.

“But I’m sure that when the researchers are set up and primed to study this more robustly, they will consider a more active control intervention to see whether this preliminary finding holds up,” she said.

Also commenting on the study, Deborah R. Glasofer, PhD, associate professor of clinical medical psychology (in psychiatry), Columbia Center for Eating Disorders, said, “Higher-than-average concern about appearance – body shape, size, or weight – and a tightly held belief that it is ideal to be thin are known risk factors for the development of an eating disorder.

“This study offers an indication that technology can be leveraged to fill a gap and help folks before unhelpful and sometimes misguided thoughts about food, eating, and appearance evolve into a full-blown eating disorder,” said Dr. Glasofer, who was not involved with the study.

The study was supported by the NEDA Feeding Hope Fund, the National Institute of Mental Health, the National Heart, Lung, and Blood Institute, and the Swedish Research Council. The authors and Dr. Glasofer have disclosed no relevant financial relationships. Dr. Attia is on the board and the Research Advisory Council of NEDA.

A version of this article first appeared on Medscape.com.

Engaging with a “chatbot,” a computer program that simulates human conversation, helps prevent eating disorders (EDs) in at-risk individuals, new research suggests.

Results of a randomized trial show that at-risk women who interacted with the chatbot showed lower concern about their weight and body shape compared to a wait-list control group.

“Chatbots are widely used in industry and have begun to be used in medical settings, although few studies have examined their effectiveness for mental health issues and none address EDs or ED prevention,” senior investigator C. Barr Taylor, MD, a research faculty member at Palo Alto (Calif.) University, said in a press release.

“We found that the group with access to the chatbot had a greater reduction in weight and shape concerns, both right after using it at 3 months and at the 6-month follow-up. The effects had sustainability over time, and we also found indication that the chatbot may reduce ED onset more so than the control group, where there was a greater incidence of EDs,” Dr. Taylor told this news organization.

The study was published online Dec. 28, 2021, in the International Journal of Eating Disorders.
 

Deadly disorders

“EDs are a common problem with huge risk factors; and, given how widespread they are, we need scalable tools that can reach a lot of people at low cost, reduce risk factors for developing an ED – which is the second most deadly of all psychiatric illnesses – so prevention is of the utmost importance,” Dr. Taylor said.

The investigators developed a targeted Internet-based preventive program called StudentBodies that utilizes cognitive-behavioral therapy approaches. The program was successful in reducing weight/shape concerns in women at high risk for the onset of an ED, and it reduced ED onset in the highest-risk women.

However, it required trained moderators who spent over 45 minutes with participants. Given the large number of people at risk for an ED who might benefit, the researchers noted that it is unlikely that a human-moderated version would be widely disseminated.

A chatbot may represent a “possible solution to reducing delivery costs” because it mimics aspects of human moderation in simulating conversations, the investigators noted.

“We wanted to take the earlier program we developed into this century and program it for delivery in this new format that would allow for bite-size pieces of information for the chatbot to communicate to the user,” lead author Ellen Fitzsimmons-Craft, PhD, assistant professor of psychiatry, Washington University, St. Louis, told this news organization.

“Our ED prevention online version was more effective when there was guidance from a human moderator who could provide feedback on progress, encourage you to go on, and apply the skills in daily life. But that’s not the most scalable. So we thought that a chatbot, in addition to providing content in this perhaps more engaging format, could also provide some aspect of human moderation, although the person is chatting with a robot,” added Dr. Fitzsimmons-Craft, associate director of the Center for Healthy Weight and Wellness.
 

Tessa will speak to you now

Participants (n = 700 women; mean [SD] age, 21.08 [3.09] years; 84.6% White; 53.8% heterosexual; 31.08% bisexual), were randomized to an intervention group or a wait-list control group (n = 352 and 348, respectively). There were no significant differences between groups in age, race, ethnicity, education, or sexual orientation.

The StudentBodies program was adapted for delivery via a chatbot named Tessa “while retaining the core intervention principles” and referred to as “Body Positive.”

It consisted of several components programmed into the chatbot, which initiated each conversation in a predetermined order. Participants were encouraged to engage in two conversations weekly. The program included an introduction and eight sessions as well as a crisis module that provided users with a referral to a crisis hotline in case of emergency. Referral was triggered on the basis of “recognized keywords,” such as “hurting myself.”

The researchers used the Weight Concerns Scale questionnaire to assess weight and shape concerns and the Internalization: Thin/Low Body Fat subscale of the Sociocultural Attitudes Toward Appearance Questionnaire–4 to “assess the cognitive aspect of thin-ideal internalization.”

Secondary outcomes tested the hypothesis that the chatbot would be more likely to reduce clinical outcomes (ED psychopathology, depression, and anxiety) and prevent ED onset, compared to the control condition.
 

Ready for prime time

At 3- and 6-month follow-up, there was significantly greater reduction in the intervention group compared with the control group in weight/shape concerns (d = -.20, P = .03 and d = -.19, P = .04, respectively), although there were no differences in thin-ideal internalization change.

The chatbot intervention was associated with significantly greater reductions in overall ED psychopathology at 3 months (d = -.29, P = .003) compared to the control condition, but not at 6 months.

Notably, the intervention group had significantly higher odds than the control group of remaining nonclinical for EDs at 3- and 6-month follow-up (OR, 2.37 [95% confidence interval, 1.37-4.11] and OR, 2.13 [95% CI,1.26-3.59], respectively).

“We were very excited about the study, and frankly, I was surprised by the effectiveness [of the chatbot intervention] because I didn’t think it would have as much of an impact as it did,” said Dr. Taylor. “Prevention gets short shrift everywhere, and I think we succeeded very well.”

Dr. Fitzsimmons-Craft added that the National Eating Disorders Association (NEDA) has agreed to make the chatbot available on its website for people who screen positive for having an ED or for being at high risk, and so their group is working with their industry partner, a company called X2AI, which developed the chatbot, to make this happen.

“This is definitely the fastest research-to-practice translation I’ve ever seen, where we can so quickly show that it works and make it available to tens of thousands almost immediately.”

Dr. Fitzsimmons-Craft is optimistic that it will be available to launch the week of Feb. 21, which is National Eating Disorders Week.
 

Innovative, creative research

Commenting on the research, Evelyn Attia, MD, professor of psychiatry, Columbia University Medical Center, and director of the Columbia Center for Eating Disorders New York–Presbyterian Hospital, New York, described the study as “innovative and creative.”

New York-Presbyterian Hospital

Dr. Attia, a member of the Research Advisory Council of the NEDA, noted that the structure of the study is “very preliminary” and that the comparison to a wait-list control makes it hard to know whether this is an effective intervention compared with other types of interventions, rather than compared with no intervention.

“But I’m sure that when the researchers are set up and primed to study this more robustly, they will consider a more active control intervention to see whether this preliminary finding holds up,” she said.

Also commenting on the study, Deborah R. Glasofer, PhD, associate professor of clinical medical psychology (in psychiatry), Columbia Center for Eating Disorders, said, “Higher-than-average concern about appearance – body shape, size, or weight – and a tightly held belief that it is ideal to be thin are known risk factors for the development of an eating disorder.

“This study offers an indication that technology can be leveraged to fill a gap and help folks before unhelpful and sometimes misguided thoughts about food, eating, and appearance evolve into a full-blown eating disorder,” said Dr. Glasofer, who was not involved with the study.

The study was supported by the NEDA Feeding Hope Fund, the National Institute of Mental Health, the National Heart, Lung, and Blood Institute, and the Swedish Research Council. The authors and Dr. Glasofer have disclosed no relevant financial relationships. Dr. Attia is on the board and the Research Advisory Council of NEDA.

A version of this article first appeared on Medscape.com.

In clinical management of depression, combining a reuptake inhibitor with presynaptic alpha2-autoreceptors significantly improves treatment outcomes, compared with monotherapy, a meta-analysis found. Clinicians should consider this approach as a viable first-line treatment for severe depression and for nonresponders, a team of German researchers concluded.

The findings were published online Feb. 16 in JAMA Psychiatry.

Combining antidepressants is often the next step if a patient with acute depression fails to respond to a monotherapy. In a previous meta-analysis, first author Jonathan Henssler, MD, and colleagues reported on the merits of combining monoamine reuptake inhibitors (selective serotonin reuptake inhibitor, serotonin-norepinephrine reuptake inhibitor [SNRI], or tricyclic antidepressant) and antagonists of presynaptic alpha2-autoreceptors (mianserin, mirtazapine, trazodone).

Studies that followed yielded mixed results. One randomized controlled trial (RCT) showed signs of substantial superiority when antidepressants were combined; another report from Japan only demonstrated a modest effect, said Christopher Baethge, MD, senior author of the meta-analysis, in an interview. Another recent trial showed better efficacy with monotherapy.

“In our view, this diverse field of trials suggested a reassessment. Specifically, we wanted to find out whether certain combinations are effective whereas others are not,” said Dr. Baethge, a professor of psychiatry at the University of Cologne (Germany).

Combing through Embase, PsycINFO, and the Cochrane Central Register of Controlled Trials, the investigators selected RCTs that compared combinations versus monotherapy antidepressants in adult patients with acute depression. The meta-analysis did not include studies on bipolar depression or maintenance therapy. It also didn’t include comorbid medical conditions and concomitant diagnoses of other psychiatric disorders as exclusion criteria.

Separate investigations of combinations using presynaptic alpha2-autoreceptor antagonists or bupropion also took place.

Treatment efficacy measured as standardized mean difference (SMD) between combination and monotherapy was the primary outcome. Other outcomes included the percent of patients in remission after either treatment course or the percentage of patients stopping drug therapy.
 

Combination treatments yield better outcomes

Among 39 trials and 6,751 patients included in the analysis, 38 of the trials provided data on the primary outcome.

Combination treatments yielded more superior outcomes, compared with monotherapy (SMD, 0.31; 95% confidence interval, 0.19-0.44). Greater efficacy in the combination approach was indicated in 82% of the studies. This finding also held up when the analysis was restricted to low risk of bias trials, applied as a first-line treatment, and among nonresponders.
 

Potential advantages of presynaptic alpha2-autoreceptors

In the separate analysis, presynaptic alpha2-autoreceptors did a better job than monotherapy as a first-line treatment and when applied to nonresponder populations. In comparison, bupropion combinations did not outperform monotherapy.

It’s possible that in combinations, “alpha2-autoreceptors effectively counteract, through sedation, the restlessness and  agitation that many patients find troublesome when taking monoamine-reuptake inhibitors. Similarly, they may help against sexual dysfunction associated with reuptake inhibitors,” Dr. Baethge suggested.

Presynaptic alpha2-autoreceptors might also boost monoaminergic neurotransmission “by interrupting the inhibition feedback loop initiated when reuptake inhibitors increase neurotransmitter concentrations in the synaptic cleft,” he added.

Whether or not bupropion combinations help patients with treatment-resistant depression is inconclusive, noted Dr. Baethge. “More studies will likely help us get a clearer picture. So far, we can only say that we have not enough evidence to positively recommend bupropion combinations to that group of patients.”

Combining treatments did not yield more dropouts or adverse events than monotherapy. “It may thus be a safe treatment alternative when compared with other second-step strategies in treatment-resistant depression, such as augmenting monotherapy with lithium or atypical psychotic,” the investigators concluded.

Looking at this study’s limitations, the multiple clinical trials examined in a meta-analysis often have different designs, definitions of response and control groups, and use different rating scales, noted Henry A. Nasrallah, MD, professor of psychiatry, neurology, and neuroscience at the University of Cincinnati, who was not involved in the study.

Some publication bias was found but overall the results kept their integrity across secondary outcomes and subgroup and sensitivity analyses.
 

Guidance for choosing more effective therapies

The hope is these results will help clinicians choose more promising combinations, such as presynaptic alpha2-autoreceptor antagonists with SSRIs or SNRIs, as opposed to combinations that are less helpful or haven’t gone through an RCT, said Dr. Baethge.

The findings on tolerability may also encourage some clinicians to consider these combinations, especially if they’ve favored less evidence-based approaches such as switching drugs or increasing the dose, he said.

Polypharmacy is often viewed as undesirable or leading to more side effects, noted Dr. Nasrallah. However, “the combination of a reuptake inhibitor plus an alpha2–presynaptic receptor antagonist like mirtazapine, can actually improve tolerability compared to monotherapy antidepressant because their mechanisms of action offset the side effects while increasing efficacy,” he said.

“Finally, although sedation is a side effect of both mirtazapine and trazodone, that can be helpful for patients with difficulty falling asleep, which is common in major depression,” added Dr. Nasrallah.

Dr. Baethge and Dr. Nasrallah had no disclosures. Dr. Henssler received a research grant from the German Federal Ministry of Education and Research.

In clinical management of depression, combining a reuptake inhibitor with presynaptic alpha2-autoreceptors significantly improves treatment outcomes, compared with monotherapy, a meta-analysis found. Clinicians should consider this approach as a viable first-line treatment for severe depression and for nonresponders, a team of German researchers concluded.

The findings were published online Feb. 16 in JAMA Psychiatry.

Combining antidepressants is often the next step if a patient with acute depression fails to respond to a monotherapy. In a previous meta-analysis, first author Jonathan Henssler, MD, and colleagues reported on the merits of combining monoamine reuptake inhibitors (selective serotonin reuptake inhibitor, serotonin-norepinephrine reuptake inhibitor [SNRI], or tricyclic antidepressant) and antagonists of presynaptic alpha2-autoreceptors (mianserin, mirtazapine, trazodone).

Studies that followed yielded mixed results. One randomized controlled trial (RCT) showed signs of substantial superiority when antidepressants were combined; another report from Japan only demonstrated a modest effect, said Christopher Baethge, MD, senior author of the meta-analysis, in an interview. Another recent trial showed better efficacy with monotherapy.

“In our view, this diverse field of trials suggested a reassessment. Specifically, we wanted to find out whether certain combinations are effective whereas others are not,” said Dr. Baethge, a professor of psychiatry at the University of Cologne (Germany).

Combing through Embase, PsycINFO, and the Cochrane Central Register of Controlled Trials, the investigators selected RCTs that compared combinations versus monotherapy antidepressants in adult patients with acute depression. The meta-analysis did not include studies on bipolar depression or maintenance therapy. It also didn’t include comorbid medical conditions and concomitant diagnoses of other psychiatric disorders as exclusion criteria.

Separate investigations of combinations using presynaptic alpha2-autoreceptor antagonists or bupropion also took place.

Treatment efficacy measured as standardized mean difference (SMD) between combination and monotherapy was the primary outcome. Other outcomes included the percent of patients in remission after either treatment course or the percentage of patients stopping drug therapy.
 

Combination treatments yield better outcomes

Among 39 trials and 6,751 patients included in the analysis, 38 of the trials provided data on the primary outcome.

Combination treatments yielded more superior outcomes, compared with monotherapy (SMD, 0.31; 95% confidence interval, 0.19-0.44). Greater efficacy in the combination approach was indicated in 82% of the studies. This finding also held up when the analysis was restricted to low risk of bias trials, applied as a first-line treatment, and among nonresponders.
 

Potential advantages of presynaptic alpha2-autoreceptors

In the separate analysis, presynaptic alpha2-autoreceptors did a better job than monotherapy as a first-line treatment and when applied to nonresponder populations. In comparison, bupropion combinations did not outperform monotherapy.

It’s possible that in combinations, “alpha2-autoreceptors effectively counteract, through sedation, the restlessness and  agitation that many patients find troublesome when taking monoamine-reuptake inhibitors. Similarly, they may help against sexual dysfunction associated with reuptake inhibitors,” Dr. Baethge suggested.

Presynaptic alpha2-autoreceptors might also boost monoaminergic neurotransmission “by interrupting the inhibition feedback loop initiated when reuptake inhibitors increase neurotransmitter concentrations in the synaptic cleft,” he added.

Whether or not bupropion combinations help patients with treatment-resistant depression is inconclusive, noted Dr. Baethge. “More studies will likely help us get a clearer picture. So far, we can only say that we have not enough evidence to positively recommend bupropion combinations to that group of patients.”

Combining treatments did not yield more dropouts or adverse events than monotherapy. “It may thus be a safe treatment alternative when compared with other second-step strategies in treatment-resistant depression, such as augmenting monotherapy with lithium or atypical psychotic,” the investigators concluded.

Looking at this study’s limitations, the multiple clinical trials examined in a meta-analysis often have different designs, definitions of response and control groups, and use different rating scales, noted Henry A. Nasrallah, MD, professor of psychiatry, neurology, and neuroscience at the University of Cincinnati, who was not involved in the study.

Some publication bias was found but overall the results kept their integrity across secondary outcomes and subgroup and sensitivity analyses.
 

Guidance for choosing more effective therapies

The hope is these results will help clinicians choose more promising combinations, such as presynaptic alpha2-autoreceptor antagonists with SSRIs or SNRIs, as opposed to combinations that are less helpful or haven’t gone through an RCT, said Dr. Baethge.

The findings on tolerability may also encourage some clinicians to consider these combinations, especially if they’ve favored less evidence-based approaches such as switching drugs or increasing the dose, he said.

Polypharmacy is often viewed as undesirable or leading to more side effects, noted Dr. Nasrallah. However, “the combination of a reuptake inhibitor plus an alpha2–presynaptic receptor antagonist like mirtazapine, can actually improve tolerability compared to monotherapy antidepressant because their mechanisms of action offset the side effects while increasing efficacy,” he said.

“Finally, although sedation is a side effect of both mirtazapine and trazodone, that can be helpful for patients with difficulty falling asleep, which is common in major depression,” added Dr. Nasrallah.

Dr. Baethge and Dr. Nasrallah had no disclosures. Dr. Henssler received a research grant from the German Federal Ministry of Education and Research.

In clinical management of depression, combining a reuptake inhibitor with presynaptic alpha2-autoreceptors significantly improves treatment outcomes, compared with monotherapy, a meta-analysis found. Clinicians should consider this approach as a viable first-line treatment for severe depression and for nonresponders, a team of German researchers concluded.

The findings were published online Feb. 16 in JAMA Psychiatry.

Combining antidepressants is often the next step if a patient with acute depression fails to respond to a monotherapy. In a previous meta-analysis, first author Jonathan Henssler, MD, and colleagues reported on the merits of combining monoamine reuptake inhibitors (selective serotonin reuptake inhibitor, serotonin-norepinephrine reuptake inhibitor [SNRI], or tricyclic antidepressant) and antagonists of presynaptic alpha2-autoreceptors (mianserin, mirtazapine, trazodone).

Studies that followed yielded mixed results. One randomized controlled trial (RCT) showed signs of substantial superiority when antidepressants were combined; another report from Japan only demonstrated a modest effect, said Christopher Baethge, MD, senior author of the meta-analysis, in an interview. Another recent trial showed better efficacy with monotherapy.

“In our view, this diverse field of trials suggested a reassessment. Specifically, we wanted to find out whether certain combinations are effective whereas others are not,” said Dr. Baethge, a professor of psychiatry at the University of Cologne (Germany).

Combing through Embase, PsycINFO, and the Cochrane Central Register of Controlled Trials, the investigators selected RCTs that compared combinations versus monotherapy antidepressants in adult patients with acute depression. The meta-analysis did not include studies on bipolar depression or maintenance therapy. It also didn’t include comorbid medical conditions and concomitant diagnoses of other psychiatric disorders as exclusion criteria.

Separate investigations of combinations using presynaptic alpha2-autoreceptor antagonists or bupropion also took place.

Treatment efficacy measured as standardized mean difference (SMD) between combination and monotherapy was the primary outcome. Other outcomes included the percent of patients in remission after either treatment course or the percentage of patients stopping drug therapy.
 

Combination treatments yield better outcomes

Among 39 trials and 6,751 patients included in the analysis, 38 of the trials provided data on the primary outcome.

Combination treatments yielded more superior outcomes, compared with monotherapy (SMD, 0.31; 95% confidence interval, 0.19-0.44). Greater efficacy in the combination approach was indicated in 82% of the studies. This finding also held up when the analysis was restricted to low risk of bias trials, applied as a first-line treatment, and among nonresponders.
 

Potential advantages of presynaptic alpha2-autoreceptors

In the separate analysis, presynaptic alpha2-autoreceptors did a better job than monotherapy as a first-line treatment and when applied to nonresponder populations. In comparison, bupropion combinations did not outperform monotherapy.

It’s possible that in combinations, “alpha2-autoreceptors effectively counteract, through sedation, the restlessness and  agitation that many patients find troublesome when taking monoamine-reuptake inhibitors. Similarly, they may help against sexual dysfunction associated with reuptake inhibitors,” Dr. Baethge suggested.

Presynaptic alpha2-autoreceptors might also boost monoaminergic neurotransmission “by interrupting the inhibition feedback loop initiated when reuptake inhibitors increase neurotransmitter concentrations in the synaptic cleft,” he added.

Whether or not bupropion combinations help patients with treatment-resistant depression is inconclusive, noted Dr. Baethge. “More studies will likely help us get a clearer picture. So far, we can only say that we have not enough evidence to positively recommend bupropion combinations to that group of patients.”

Combining treatments did not yield more dropouts or adverse events than monotherapy. “It may thus be a safe treatment alternative when compared with other second-step strategies in treatment-resistant depression, such as augmenting monotherapy with lithium or atypical psychotic,” the investigators concluded.

Looking at this study’s limitations, the multiple clinical trials examined in a meta-analysis often have different designs, definitions of response and control groups, and use different rating scales, noted Henry A. Nasrallah, MD, professor of psychiatry, neurology, and neuroscience at the University of Cincinnati, who was not involved in the study.

Some publication bias was found but overall the results kept their integrity across secondary outcomes and subgroup and sensitivity analyses.
 

Guidance for choosing more effective therapies

The hope is these results will help clinicians choose more promising combinations, such as presynaptic alpha2-autoreceptor antagonists with SSRIs or SNRIs, as opposed to combinations that are less helpful or haven’t gone through an RCT, said Dr. Baethge.

The findings on tolerability may also encourage some clinicians to consider these combinations, especially if they’ve favored less evidence-based approaches such as switching drugs or increasing the dose, he said.

Polypharmacy is often viewed as undesirable or leading to more side effects, noted Dr. Nasrallah. However, “the combination of a reuptake inhibitor plus an alpha2–presynaptic receptor antagonist like mirtazapine, can actually improve tolerability compared to monotherapy antidepressant because their mechanisms of action offset the side effects while increasing efficacy,” he said.

“Finally, although sedation is a side effect of both mirtazapine and trazodone, that can be helpful for patients with difficulty falling asleep, which is common in major depression,” added Dr. Nasrallah.

Dr. Baethge and Dr. Nasrallah had no disclosures. Dr. Henssler received a research grant from the German Federal Ministry of Education and Research.

Seizure phobia occurs in nearly one-third of people with epilepsy (PWE), but was mainly associated with variables not related to epilepsy, based on data from 69 adults.

Anxiety and depression are known to affect quality of life in epilepsy patients, and previous studies have shown that anticipatory anxiety of epileptic seizures (AAS) was present in 53% of patients with focal epilepsy, wrote lead author Aviva Weiss of Psychiatric Hostels affiliated with Kidum Rehabilitation Projects, Jerusalem, and colleagues.

“Although recognized by the epilepsy and the psychiatric communities, seizure phobia as a distinct anxiety disorder among PWE is insufficiently described in the medical literature,” they said.

Seizure phobia has been defined as an anxiety disorder in which patients experience fear related to anticipation of seizures in certain situations.

In a study published in Seizure: European Journal of Epilepsy, the researchers recruited 69 PWE who were treated at an outpatient clinic. Data were collected from interviews, questionnaires, and medical records. The average age of the participants was 36.8 years, 41 were women, and 41 were married.

Overall, 19 individuals (27.5%) were diagnosed with seizure phobia. Compared with PWE without seizure phobia, the seizure phobia patients were significantly more likely to be women (84.2% vs. 44.2%; P = .005) and to have comorbid anxiety disorders (84.2% vs. 34.9%; P = .01). Individuals with seizure phobia also were significantly more likely than those without seizure phobia to have a past major depressive episode (63.2% vs. 20.9%; P = .003), and posttraumatic stress disorder (26.3% vs. 7%; P = .05).

Seizure phobia was significantly associated with comorbid psychogenic nonepileptic seizures (PNES) (36.8% vs. 11.6%; P = .034). PNES have been significantly associated with panic attacks, and “all patients with both panic attacks and comorbid PNES were diagnosed with seizure phobia,” the researchers noted. However, no significant association was found with epilepsy-related variables, they said.

A multivariate logistic regression model to predict seizure phobia showed that anxiety and a past MDE were significant predictors; the odds of seizure phobia were 10.45 times higher if a patient reported any anxiety disorder, and 6.85 times higher if the patient had a history of MDE.

The study findings were limited by several factors, including the use of semistructured interviews to diagnose seizure phobia, which are subject to interviewer bias, and by the small study population with a high proportion of comorbid PNES and epilepsy, the researchers noted. However, the results support seizure phobia as a distinct clinical entity worthy of management with education, psychosocial interventions, and potential medication changes, they said.

“Development of appropriate screening tools and implementation of effective treatment interventions is warranted for individual patients, combined with large-scale population-targeted psychoeducation, aimed to mitigate the risk of developing seizure phobia in PWE,” they concluded.

The study received no outside funding. The researchers had no financial conflicts to disclose.
 

Seizure phobia occurs in nearly one-third of people with epilepsy (PWE), but was mainly associated with variables not related to epilepsy, based on data from 69 adults.

Anxiety and depression are known to affect quality of life in epilepsy patients, and previous studies have shown that anticipatory anxiety of epileptic seizures (AAS) was present in 53% of patients with focal epilepsy, wrote lead author Aviva Weiss of Psychiatric Hostels affiliated with Kidum Rehabilitation Projects, Jerusalem, and colleagues.

“Although recognized by the epilepsy and the psychiatric communities, seizure phobia as a distinct anxiety disorder among PWE is insufficiently described in the medical literature,” they said.

Seizure phobia has been defined as an anxiety disorder in which patients experience fear related to anticipation of seizures in certain situations.

In a study published in Seizure: European Journal of Epilepsy, the researchers recruited 69 PWE who were treated at an outpatient clinic. Data were collected from interviews, questionnaires, and medical records. The average age of the participants was 36.8 years, 41 were women, and 41 were married.

Overall, 19 individuals (27.5%) were diagnosed with seizure phobia. Compared with PWE without seizure phobia, the seizure phobia patients were significantly more likely to be women (84.2% vs. 44.2%; P = .005) and to have comorbid anxiety disorders (84.2% vs. 34.9%; P = .01). Individuals with seizure phobia also were significantly more likely than those without seizure phobia to have a past major depressive episode (63.2% vs. 20.9%; P = .003), and posttraumatic stress disorder (26.3% vs. 7%; P = .05).

Seizure phobia was significantly associated with comorbid psychogenic nonepileptic seizures (PNES) (36.8% vs. 11.6%; P = .034). PNES have been significantly associated with panic attacks, and “all patients with both panic attacks and comorbid PNES were diagnosed with seizure phobia,” the researchers noted. However, no significant association was found with epilepsy-related variables, they said.

A multivariate logistic regression model to predict seizure phobia showed that anxiety and a past MDE were significant predictors; the odds of seizure phobia were 10.45 times higher if a patient reported any anxiety disorder, and 6.85 times higher if the patient had a history of MDE.

The study findings were limited by several factors, including the use of semistructured interviews to diagnose seizure phobia, which are subject to interviewer bias, and by the small study population with a high proportion of comorbid PNES and epilepsy, the researchers noted. However, the results support seizure phobia as a distinct clinical entity worthy of management with education, psychosocial interventions, and potential medication changes, they said.

“Development of appropriate screening tools and implementation of effective treatment interventions is warranted for individual patients, combined with large-scale population-targeted psychoeducation, aimed to mitigate the risk of developing seizure phobia in PWE,” they concluded.

The study received no outside funding. The researchers had no financial conflicts to disclose.
 

Seizure phobia occurs in nearly one-third of people with epilepsy (PWE), but was mainly associated with variables not related to epilepsy, based on data from 69 adults.

Anxiety and depression are known to affect quality of life in epilepsy patients, and previous studies have shown that anticipatory anxiety of epileptic seizures (AAS) was present in 53% of patients with focal epilepsy, wrote lead author Aviva Weiss of Psychiatric Hostels affiliated with Kidum Rehabilitation Projects, Jerusalem, and colleagues.

“Although recognized by the epilepsy and the psychiatric communities, seizure phobia as a distinct anxiety disorder among PWE is insufficiently described in the medical literature,” they said.

Seizure phobia has been defined as an anxiety disorder in which patients experience fear related to anticipation of seizures in certain situations.

In a study published in Seizure: European Journal of Epilepsy, the researchers recruited 69 PWE who were treated at an outpatient clinic. Data were collected from interviews, questionnaires, and medical records. The average age of the participants was 36.8 years, 41 were women, and 41 were married.

Overall, 19 individuals (27.5%) were diagnosed with seizure phobia. Compared with PWE without seizure phobia, the seizure phobia patients were significantly more likely to be women (84.2% vs. 44.2%; P = .005) and to have comorbid anxiety disorders (84.2% vs. 34.9%; P = .01). Individuals with seizure phobia also were significantly more likely than those without seizure phobia to have a past major depressive episode (63.2% vs. 20.9%; P = .003), and posttraumatic stress disorder (26.3% vs. 7%; P = .05).

Seizure phobia was significantly associated with comorbid psychogenic nonepileptic seizures (PNES) (36.8% vs. 11.6%; P = .034). PNES have been significantly associated with panic attacks, and “all patients with both panic attacks and comorbid PNES were diagnosed with seizure phobia,” the researchers noted. However, no significant association was found with epilepsy-related variables, they said.

A multivariate logistic regression model to predict seizure phobia showed that anxiety and a past MDE were significant predictors; the odds of seizure phobia were 10.45 times higher if a patient reported any anxiety disorder, and 6.85 times higher if the patient had a history of MDE.

The study findings were limited by several factors, including the use of semistructured interviews to diagnose seizure phobia, which are subject to interviewer bias, and by the small study population with a high proportion of comorbid PNES and epilepsy, the researchers noted. However, the results support seizure phobia as a distinct clinical entity worthy of management with education, psychosocial interventions, and potential medication changes, they said.

“Development of appropriate screening tools and implementation of effective treatment interventions is warranted for individual patients, combined with large-scale population-targeted psychoeducation, aimed to mitigate the risk of developing seizure phobia in PWE,” they concluded.

The study received no outside funding. The researchers had no financial conflicts to disclose.
 

This month’s column is driven by the recent increase of youth in crisis, and COVID-19–related limitations of higher-level services. Suicide is the second leading cause of death among youth¹ and populations who face discrimination are at increased risk.^2,3

A pediatrician colleague recently asked me about how to support patients who may be at risk. With inpatient units and emergency departments over capacity, properly allocating resources to patients with the most acute needs is crucial. When appropriate, providing preventive suicide care in primary care similarly saves lives.
 

Case summary

Cassandra is a 16-year-old Black girl who told a friend on Snapchat that she did not want to be alive. The friend told her parents and Cassandra’s parents brought their daughter to an urgent primary care appointment. Cassandra has had a history of difficulty with large transitions like a family move when she was 13. She spent more time in her room for several months before joining the volleyball team and making new friends. She has always done well academically in school but struggled with insomnia and classwork when her high school shifted to remote learning for the 2020-2021 school year because of the pandemic. This year she attends school in person but is unable to play volleyball because of COVID-19 restrictions. Her parents report that she is again spending more time online in her room. She is passing her classes and doing well in math, but overall, her grades have fallen since the pandemic began. She reports recent difficulties with friends and notes feeling hopeless about a changing climate and race relations in the United States.

Discussion

This case example illustrates some factors pediatricians can consider in determining how to proceed in similar circumstances. What are Cassandra’s immediate risk and treatment needs? In cases like Cassandra’s, the American Academy of Pediatrics recommends the ABCD (Assess, Build hope, Connect, Develop a safety plan) approach.⁴ Preparing practices to deliver this best possible preventive suicide care is essential.

1. Is this patient at imminent risk of harming herself?

Assess: Screen for suicide risk and assess risk level. Several standardized screening tools exist for gauging a patient’s risk. The Ask Suicide Screening Questionnaire (asQ) is a straightforward screening tool (not to be confused with the ASQ Ages and Stages developmental screening). These questionnaires take only a few minutes and next steps are suggested depending on the score (low, moderate, or high risk) and clinical judgment. What matters most is using a standardized screener to directly ask questions about suicide and then follow up appropriately based on risk.

2. What can be done during the visit to promote a good outcome?

Build hope/reasons for living. Validate that people sometimes feel suicidal when things are difficult, but that the feelings come and go and people go on to live meaningful lives. Tell the patients that you care about keeping them safe when the feelings come up. Motivational interviewing can be helpful to reflect back patient-identified reasons for living. Genuinely tell the patients how much you care about their wellbeing.

3. What can be done outside the visit to promote a good outcome?

Connect: Strengthen connections with protective adults. Make a plan to have the patient connect regularly with parents/trusted adults. She could engage in social action, or connect one-on-one. With more structured social opportunities, she will spend less time online. Medical practices can reach out with postcards and phone calls to show that they care about the patient, an intervention called “Caring Contacts” that has been shown to decrease suicide.

4. Once suicide risk is identified, what are specific tools to use during the visit to keep her safe?

Develop a plan for staying safe: Restrict access to lethal means, develop a safety plan and healthy ways of coping. There is a free 2-hour CALM (Counseling on Access to Lethal Means) training to help providers feel competent in restricting access to lethal means prior to increased risk. This resource provides safety plan templates that help identify triggers, specific ways to stay safe, people to talk to, and suicide prevention resources including lifelines (988) and chat options (text 2 letter state to 741741).

Enacting suicide prevention requires practice readiness and workflow changes. Providers should assess mental health supports in and out of the office, and then rehearse workflow around suicide prevention care. Increasingly, there are embedded case managers or behavioral health providers available. Sometimes local mental health crisis services are the best option. A practice introductory letter to community mental health practitioners can improve later coordination efforts when caring for suicidal youth. Having practice-level support for provider well-being can improve outcomes.
 

Case follow-up

After interviewing the girl separately, and performing a PHQ-A and an asQ, followed by the Brief Suicide Safety Assessment to screen for acuity, the pediatrician felt confident that Cassandra was suffering from moderate depression and had moderate but not imminent risk of suicide. Options to treat her depression were discussed with Cassandra and her parents, and a referral to therapy was made.

The provider knew that depression care is complementary but not sufficient as standalone suicide prevention. The provider used the asQ pathway to determine next steps. He made a safety plan, and referred her to an outpatient mental health clinician with whom the practice had an established relationship for an urgent mental health evaluation. A follow-up primary care appointment was scheduled within 72 hours to re-check safety and ensure that she had an appointment scheduled to start therapy. A nurse contacted the patient and her family regularly to check on her wellbeing. Her parents made a plan with her volleyball coach to organize outdoor off-season conditioning to help with exercise and socializing. The family removed screens prior to bedtime and sleep improved. At a 3-month follow-up, Cassandra had only mild depressive symptoms and the frequency and intensity of her suicidal ideation had decreased.
 

Dr. Spottswood is a child psychiatrist practicing in an integrated care clinic at the Community Health Centers of Burlington, Vermont, a Federally Qualified Health Center. She is the medical director of the Vermont Child Psychiatry Access Program and a clinical assistant professor in the department of psychiatry at the University of Vermont.
 

References

1. National Institute of Mental Health: Suicide.

2. Hottes TS et al. Am J Public Health. 2016 May;106(5):e1-12.

3. Bridge JA et al. JAMA Pediatr. 2018;172(7):697-9.

4. Asarnow JR. SAMHSA Center for Adolescent Suicide and Self-Harm..

This month’s column is driven by the recent increase of youth in crisis, and COVID-19–related limitations of higher-level services. Suicide is the second leading cause of death among youth¹ and populations who face discrimination are at increased risk.^2,3

A pediatrician colleague recently asked me about how to support patients who may be at risk. With inpatient units and emergency departments over capacity, properly allocating resources to patients with the most acute needs is crucial. When appropriate, providing preventive suicide care in primary care similarly saves lives.
 

Case summary

Cassandra is a 16-year-old Black girl who told a friend on Snapchat that she did not want to be alive. The friend told her parents and Cassandra’s parents brought their daughter to an urgent primary care appointment. Cassandra has had a history of difficulty with large transitions like a family move when she was 13. She spent more time in her room for several months before joining the volleyball team and making new friends. She has always done well academically in school but struggled with insomnia and classwork when her high school shifted to remote learning for the 2020-2021 school year because of the pandemic. This year she attends school in person but is unable to play volleyball because of COVID-19 restrictions. Her parents report that she is again spending more time online in her room. She is passing her classes and doing well in math, but overall, her grades have fallen since the pandemic began. She reports recent difficulties with friends and notes feeling hopeless about a changing climate and race relations in the United States.

Discussion

This case example illustrates some factors pediatricians can consider in determining how to proceed in similar circumstances. What are Cassandra’s immediate risk and treatment needs? In cases like Cassandra’s, the American Academy of Pediatrics recommends the ABCD (Assess, Build hope, Connect, Develop a safety plan) approach.⁴ Preparing practices to deliver this best possible preventive suicide care is essential.

1. Is this patient at imminent risk of harming herself?

Assess: Screen for suicide risk and assess risk level. Several standardized screening tools exist for gauging a patient’s risk. The Ask Suicide Screening Questionnaire (asQ) is a straightforward screening tool (not to be confused with the ASQ Ages and Stages developmental screening). These questionnaires take only a few minutes and next steps are suggested depending on the score (low, moderate, or high risk) and clinical judgment. What matters most is using a standardized screener to directly ask questions about suicide and then follow up appropriately based on risk.

2. What can be done during the visit to promote a good outcome?

Build hope/reasons for living. Validate that people sometimes feel suicidal when things are difficult, but that the feelings come and go and people go on to live meaningful lives. Tell the patients that you care about keeping them safe when the feelings come up. Motivational interviewing can be helpful to reflect back patient-identified reasons for living. Genuinely tell the patients how much you care about their wellbeing.

3. What can be done outside the visit to promote a good outcome?

Connect: Strengthen connections with protective adults. Make a plan to have the patient connect regularly with parents/trusted adults. She could engage in social action, or connect one-on-one. With more structured social opportunities, she will spend less time online. Medical practices can reach out with postcards and phone calls to show that they care about the patient, an intervention called “Caring Contacts” that has been shown to decrease suicide.

4. Once suicide risk is identified, what are specific tools to use during the visit to keep her safe?

Develop a plan for staying safe: Restrict access to lethal means, develop a safety plan and healthy ways of coping. There is a free 2-hour CALM (Counseling on Access to Lethal Means) training to help providers feel competent in restricting access to lethal means prior to increased risk. This resource provides safety plan templates that help identify triggers, specific ways to stay safe, people to talk to, and suicide prevention resources including lifelines (988) and chat options (text 2 letter state to 741741).

Enacting suicide prevention requires practice readiness and workflow changes. Providers should assess mental health supports in and out of the office, and then rehearse workflow around suicide prevention care. Increasingly, there are embedded case managers or behavioral health providers available. Sometimes local mental health crisis services are the best option. A practice introductory letter to community mental health practitioners can improve later coordination efforts when caring for suicidal youth. Having practice-level support for provider well-being can improve outcomes.
 

Case follow-up

After interviewing the girl separately, and performing a PHQ-A and an asQ, followed by the Brief Suicide Safety Assessment to screen for acuity, the pediatrician felt confident that Cassandra was suffering from moderate depression and had moderate but not imminent risk of suicide. Options to treat her depression were discussed with Cassandra and her parents, and a referral to therapy was made.

The provider knew that depression care is complementary but not sufficient as standalone suicide prevention. The provider used the asQ pathway to determine next steps. He made a safety plan, and referred her to an outpatient mental health clinician with whom the practice had an established relationship for an urgent mental health evaluation. A follow-up primary care appointment was scheduled within 72 hours to re-check safety and ensure that she had an appointment scheduled to start therapy. A nurse contacted the patient and her family regularly to check on her wellbeing. Her parents made a plan with her volleyball coach to organize outdoor off-season conditioning to help with exercise and socializing. The family removed screens prior to bedtime and sleep improved. At a 3-month follow-up, Cassandra had only mild depressive symptoms and the frequency and intensity of her suicidal ideation had decreased.
 

Dr. Spottswood is a child psychiatrist practicing in an integrated care clinic at the Community Health Centers of Burlington, Vermont, a Federally Qualified Health Center. She is the medical director of the Vermont Child Psychiatry Access Program and a clinical assistant professor in the department of psychiatry at the University of Vermont.
 

References

1. National Institute of Mental Health: Suicide.

2. Hottes TS et al. Am J Public Health. 2016 May;106(5):e1-12.

3. Bridge JA et al. JAMA Pediatr. 2018;172(7):697-9.

4. Asarnow JR. SAMHSA Center for Adolescent Suicide and Self-Harm..

This month’s column is driven by the recent increase of youth in crisis, and COVID-19–related limitations of higher-level services. Suicide is the second leading cause of death among youth¹ and populations who face discrimination are at increased risk.^2,3

A pediatrician colleague recently asked me about how to support patients who may be at risk. With inpatient units and emergency departments over capacity, properly allocating resources to patients with the most acute needs is crucial. When appropriate, providing preventive suicide care in primary care similarly saves lives.
 

Case summary

Cassandra is a 16-year-old Black girl who told a friend on Snapchat that she did not want to be alive. The friend told her parents and Cassandra’s parents brought their daughter to an urgent primary care appointment. Cassandra has had a history of difficulty with large transitions like a family move when she was 13. She spent more time in her room for several months before joining the volleyball team and making new friends. She has always done well academically in school but struggled with insomnia and classwork when her high school shifted to remote learning for the 2020-2021 school year because of the pandemic. This year she attends school in person but is unable to play volleyball because of COVID-19 restrictions. Her parents report that she is again spending more time online in her room. She is passing her classes and doing well in math, but overall, her grades have fallen since the pandemic began. She reports recent difficulties with friends and notes feeling hopeless about a changing climate and race relations in the United States.

Discussion

This case example illustrates some factors pediatricians can consider in determining how to proceed in similar circumstances. What are Cassandra’s immediate risk and treatment needs? In cases like Cassandra’s, the American Academy of Pediatrics recommends the ABCD (Assess, Build hope, Connect, Develop a safety plan) approach.⁴ Preparing practices to deliver this best possible preventive suicide care is essential.

1. Is this patient at imminent risk of harming herself?

Assess: Screen for suicide risk and assess risk level. Several standardized screening tools exist for gauging a patient’s risk. The Ask Suicide Screening Questionnaire (asQ) is a straightforward screening tool (not to be confused with the ASQ Ages and Stages developmental screening). These questionnaires take only a few minutes and next steps are suggested depending on the score (low, moderate, or high risk) and clinical judgment. What matters most is using a standardized screener to directly ask questions about suicide and then follow up appropriately based on risk.

2. What can be done during the visit to promote a good outcome?

Build hope/reasons for living. Validate that people sometimes feel suicidal when things are difficult, but that the feelings come and go and people go on to live meaningful lives. Tell the patients that you care about keeping them safe when the feelings come up. Motivational interviewing can be helpful to reflect back patient-identified reasons for living. Genuinely tell the patients how much you care about their wellbeing.

3. What can be done outside the visit to promote a good outcome?

Connect: Strengthen connections with protective adults. Make a plan to have the patient connect regularly with parents/trusted adults. She could engage in social action, or connect one-on-one. With more structured social opportunities, she will spend less time online. Medical practices can reach out with postcards and phone calls to show that they care about the patient, an intervention called “Caring Contacts” that has been shown to decrease suicide.

4. Once suicide risk is identified, what are specific tools to use during the visit to keep her safe?

Develop a plan for staying safe: Restrict access to lethal means, develop a safety plan and healthy ways of coping. There is a free 2-hour CALM (Counseling on Access to Lethal Means) training to help providers feel competent in restricting access to lethal means prior to increased risk. This resource provides safety plan templates that help identify triggers, specific ways to stay safe, people to talk to, and suicide prevention resources including lifelines (988) and chat options (text 2 letter state to 741741).

Enacting suicide prevention requires practice readiness and workflow changes. Providers should assess mental health supports in and out of the office, and then rehearse workflow around suicide prevention care. Increasingly, there are embedded case managers or behavioral health providers available. Sometimes local mental health crisis services are the best option. A practice introductory letter to community mental health practitioners can improve later coordination efforts when caring for suicidal youth. Having practice-level support for provider well-being can improve outcomes.
 

Case follow-up

After interviewing the girl separately, and performing a PHQ-A and an asQ, followed by the Brief Suicide Safety Assessment to screen for acuity, the pediatrician felt confident that Cassandra was suffering from moderate depression and had moderate but not imminent risk of suicide. Options to treat her depression were discussed with Cassandra and her parents, and a referral to therapy was made.

The provider knew that depression care is complementary but not sufficient as standalone suicide prevention. The provider used the asQ pathway to determine next steps. He made a safety plan, and referred her to an outpatient mental health clinician with whom the practice had an established relationship for an urgent mental health evaluation. A follow-up primary care appointment was scheduled within 72 hours to re-check safety and ensure that she had an appointment scheduled to start therapy. A nurse contacted the patient and her family regularly to check on her wellbeing. Her parents made a plan with her volleyball coach to organize outdoor off-season conditioning to help with exercise and socializing. The family removed screens prior to bedtime and sleep improved. At a 3-month follow-up, Cassandra had only mild depressive symptoms and the frequency and intensity of her suicidal ideation had decreased.
 

Dr. Spottswood is a child psychiatrist practicing in an integrated care clinic at the Community Health Centers of Burlington, Vermont, a Federally Qualified Health Center. She is the medical director of the Vermont Child Psychiatry Access Program and a clinical assistant professor in the department of psychiatry at the University of Vermont.
 

References

1. National Institute of Mental Health: Suicide.

2. Hottes TS et al. Am J Public Health. 2016 May;106(5):e1-12.

3. Bridge JA et al. JAMA Pediatr. 2018;172(7):697-9.

4. Asarnow JR. SAMHSA Center for Adolescent Suicide and Self-Harm..

Ketamine is a rapid and effective treatment for suicidal ideation and has a “major” moderating effect based on the primary mental health diagnosis, results of a large randomized controlled trial show.

In addition, a strong effect of ketamine was observed in patients with bipolar disorder, “whereas the effect was moderate and did not quite reach significance in those with other psychiatric disorders and unexpectedly was nonsignificant in those with major depressive disorders,” the researchers wrote.

“We assessed for the first time in the same study the effect of ketamine on three a priori–defined groups of nonpsychotic patients: those with a bipolar disorder, those with a depressive disorder, and those with other diagnoses,” study investigator Fabrice Jollant, MD, PhD, professor of psychiatry, University of Paris, said in an interview.

“This allowed us to find that comorbid disorders are important modulators of the clinical effects of ketamine, and that the effect of ketamine is particularly marked among patients with a bipolar disorder,” Dr. Jollant added.  

The study was published online Feb. 2, 2022, in the BMJ.
 

Swift, full remission

The study included 156 adults admitted voluntarily to seven French teaching hospitals with severe suicidal ideation, including 52 with bipolar disorder, 56 with depressive disorder, and 48 with other psychiatric diagnoses.

They were randomly allocated to two 40-minute intravenous infusions of ketamine (0.5 mg/kg) or placebo (saline) administered at baseline and 24 hours, in addition to usual treatment. 

The primary outcome was the rate of patients in full suicidal remission at day 3, confirmed by a score of 3 or less on a clinician-rated scale for suicidal ideation based on 19 items scored 0-2 (maximum score, 38).

“We investigated the full remission of suicidal ideas and not only the response, which is usually defined as a reduction of 50% of scores on a given scale. If people remain slightly suicidal, the suicidal risk persists. We want all suicidal ideas to disappear,” said Dr. Jollant.

They found that more patients reached full remission of suicidal ideas at day 3 after two ketamine infusions than after placebo infusions (63% vs. 32%; odds ratio, 3.7; 95% confidence interval, 1.9-7.3; P < .001).

This antisuicidal effect of ketamine was rapid, with 44% remission only 2 hours after the first infusion, the authors reported.

The effect of ketamine on suicidal remission was greatest in patients with bipolar disorder, with 85% achieving full remission at day 3 (OR, 14.1; 95% CI, 3.0-92.2; P < .001), compared with 42% of patients with depressive disorder (OR, 1.3; 95% CI, 0.3-5.2; P = .6) or 62% of those with other disorders (OR, 3.7; 95% CI, 0.9-17.3; P = .07).

At 6 weeks after treatment, remission in the ketamine group remained high, although nonsignificantly versus placebo (69.5% vs. 56.3%; OR, 0.8; 95% CI, 0.3-2.5; P = .7).

The researchers noted the beneficial effect of ketamine on suicidal ideation could be mediated by an effect on psychological pain.

“Although mental pain does not necessarily lead to suicidal ideas, recent studies suggest that individuals with severe suicidal ideas (notably those with a plan) also have high levels of mental pain. Ketamine might therefore exert its effects through analgesic mechanisms that reduce mental pain,” they wrote.

Ketamine’s side effects were “limited” with no manic or psychotic symptoms seen. The main side effects, including sedation, denationalization/derealization, nausea, and dizziness, were of short duration and occurred in about 10% or fewer patients.

The investigators acknowledged that the nonsignificant effect of ketamine in the patients with major depressive disorders in this study is “challenging to interpret.”

They pointed out the study may have lacked power to detect an effect in these patients. In addition, this group might be particularly heterogeneous, with more patients sensitive to a placebo effect and more patients requiring repeated ketamine infusions.
 

A new perspective on ketamine

In an accompanying editorial, Riccardo De Giorgi, MD, Wellcome Trust doctoral training fellow, department of psychiatry, University of Oxford (England), said the study challenges current thinking about ketamine.

The “unexpected” outcome (no benefit) in the depressive group “perhaps defies the prevailing notion that patients with major depression would benefit most from ketamine,” Dr. De Giorgi wrote.

“In fact, both usual care and ketamine given with usual care led to low, comparable remission rates of 35.7% and 42.3% for suicidal ideation, respectively, in patients with depressive disorder,” Dr. De Giorgi pointed out.

“While this study therefore confirms that many patients with depressive disorder and suicidal ideation remain poorly served by available treatments, it shows that another important group of patients with acute suicidal ideation, those with bipolar disorder, could benefit from ketamine,” Dr. De Giorgi wrote.

“Once again, here is evidence that careful clinical evaluation must precede any consideration of ketamine use, which must be reserved for specific clinical presentations and not given indiscriminately to anyone presenting with suicidal thoughts,” he concluded.

Funding for the study was provided by Programme Hospitalier de Recherche Clinique National. Dr. Jollant and Dr. De Giorgi disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Ketamine is a rapid and effective treatment for suicidal ideation and has a “major” moderating effect based on the primary mental health diagnosis, results of a large randomized controlled trial show.

In addition, a strong effect of ketamine was observed in patients with bipolar disorder, “whereas the effect was moderate and did not quite reach significance in those with other psychiatric disorders and unexpectedly was nonsignificant in those with major depressive disorders,” the researchers wrote.

“We assessed for the first time in the same study the effect of ketamine on three a priori–defined groups of nonpsychotic patients: those with a bipolar disorder, those with a depressive disorder, and those with other diagnoses,” study investigator Fabrice Jollant, MD, PhD, professor of psychiatry, University of Paris, said in an interview.

“This allowed us to find that comorbid disorders are important modulators of the clinical effects of ketamine, and that the effect of ketamine is particularly marked among patients with a bipolar disorder,” Dr. Jollant added.  

The study was published online Feb. 2, 2022, in the BMJ.
 

Swift, full remission

The study included 156 adults admitted voluntarily to seven French teaching hospitals with severe suicidal ideation, including 52 with bipolar disorder, 56 with depressive disorder, and 48 with other psychiatric diagnoses.

They were randomly allocated to two 40-minute intravenous infusions of ketamine (0.5 mg/kg) or placebo (saline) administered at baseline and 24 hours, in addition to usual treatment. 

The primary outcome was the rate of patients in full suicidal remission at day 3, confirmed by a score of 3 or less on a clinician-rated scale for suicidal ideation based on 19 items scored 0-2 (maximum score, 38).

“We investigated the full remission of suicidal ideas and not only the response, which is usually defined as a reduction of 50% of scores on a given scale. If people remain slightly suicidal, the suicidal risk persists. We want all suicidal ideas to disappear,” said Dr. Jollant.

They found that more patients reached full remission of suicidal ideas at day 3 after two ketamine infusions than after placebo infusions (63% vs. 32%; odds ratio, 3.7; 95% confidence interval, 1.9-7.3; P < .001).

This antisuicidal effect of ketamine was rapid, with 44% remission only 2 hours after the first infusion, the authors reported.

The effect of ketamine on suicidal remission was greatest in patients with bipolar disorder, with 85% achieving full remission at day 3 (OR, 14.1; 95% CI, 3.0-92.2; P < .001), compared with 42% of patients with depressive disorder (OR, 1.3; 95% CI, 0.3-5.2; P = .6) or 62% of those with other disorders (OR, 3.7; 95% CI, 0.9-17.3; P = .07).

At 6 weeks after treatment, remission in the ketamine group remained high, although nonsignificantly versus placebo (69.5% vs. 56.3%; OR, 0.8; 95% CI, 0.3-2.5; P = .7).

The researchers noted the beneficial effect of ketamine on suicidal ideation could be mediated by an effect on psychological pain.

“Although mental pain does not necessarily lead to suicidal ideas, recent studies suggest that individuals with severe suicidal ideas (notably those with a plan) also have high levels of mental pain. Ketamine might therefore exert its effects through analgesic mechanisms that reduce mental pain,” they wrote.

Ketamine’s side effects were “limited” with no manic or psychotic symptoms seen. The main side effects, including sedation, denationalization/derealization, nausea, and dizziness, were of short duration and occurred in about 10% or fewer patients.

The investigators acknowledged that the nonsignificant effect of ketamine in the patients with major depressive disorders in this study is “challenging to interpret.”

They pointed out the study may have lacked power to detect an effect in these patients. In addition, this group might be particularly heterogeneous, with more patients sensitive to a placebo effect and more patients requiring repeated ketamine infusions.
 

A new perspective on ketamine

In an accompanying editorial, Riccardo De Giorgi, MD, Wellcome Trust doctoral training fellow, department of psychiatry, University of Oxford (England), said the study challenges current thinking about ketamine.

The “unexpected” outcome (no benefit) in the depressive group “perhaps defies the prevailing notion that patients with major depression would benefit most from ketamine,” Dr. De Giorgi wrote.

“In fact, both usual care and ketamine given with usual care led to low, comparable remission rates of 35.7% and 42.3% for suicidal ideation, respectively, in patients with depressive disorder,” Dr. De Giorgi pointed out.

“While this study therefore confirms that many patients with depressive disorder and suicidal ideation remain poorly served by available treatments, it shows that another important group of patients with acute suicidal ideation, those with bipolar disorder, could benefit from ketamine,” Dr. De Giorgi wrote.

“Once again, here is evidence that careful clinical evaluation must precede any consideration of ketamine use, which must be reserved for specific clinical presentations and not given indiscriminately to anyone presenting with suicidal thoughts,” he concluded.

Funding for the study was provided by Programme Hospitalier de Recherche Clinique National. Dr. Jollant and Dr. De Giorgi disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Ketamine is a rapid and effective treatment for suicidal ideation and has a “major” moderating effect based on the primary mental health diagnosis, results of a large randomized controlled trial show.

In addition, a strong effect of ketamine was observed in patients with bipolar disorder, “whereas the effect was moderate and did not quite reach significance in those with other psychiatric disorders and unexpectedly was nonsignificant in those with major depressive disorders,” the researchers wrote.

“We assessed for the first time in the same study the effect of ketamine on three a priori–defined groups of nonpsychotic patients: those with a bipolar disorder, those with a depressive disorder, and those with other diagnoses,” study investigator Fabrice Jollant, MD, PhD, professor of psychiatry, University of Paris, said in an interview.

“This allowed us to find that comorbid disorders are important modulators of the clinical effects of ketamine, and that the effect of ketamine is particularly marked among patients with a bipolar disorder,” Dr. Jollant added.  

The study was published online Feb. 2, 2022, in the BMJ.
 

Swift, full remission

The study included 156 adults admitted voluntarily to seven French teaching hospitals with severe suicidal ideation, including 52 with bipolar disorder, 56 with depressive disorder, and 48 with other psychiatric diagnoses.

They were randomly allocated to two 40-minute intravenous infusions of ketamine (0.5 mg/kg) or placebo (saline) administered at baseline and 24 hours, in addition to usual treatment. 

The primary outcome was the rate of patients in full suicidal remission at day 3, confirmed by a score of 3 or less on a clinician-rated scale for suicidal ideation based on 19 items scored 0-2 (maximum score, 38).

“We investigated the full remission of suicidal ideas and not only the response, which is usually defined as a reduction of 50% of scores on a given scale. If people remain slightly suicidal, the suicidal risk persists. We want all suicidal ideas to disappear,” said Dr. Jollant.

They found that more patients reached full remission of suicidal ideas at day 3 after two ketamine infusions than after placebo infusions (63% vs. 32%; odds ratio, 3.7; 95% confidence interval, 1.9-7.3; P < .001).

This antisuicidal effect of ketamine was rapid, with 44% remission only 2 hours after the first infusion, the authors reported.

The effect of ketamine on suicidal remission was greatest in patients with bipolar disorder, with 85% achieving full remission at day 3 (OR, 14.1; 95% CI, 3.0-92.2; P < .001), compared with 42% of patients with depressive disorder (OR, 1.3; 95% CI, 0.3-5.2; P = .6) or 62% of those with other disorders (OR, 3.7; 95% CI, 0.9-17.3; P = .07).

At 6 weeks after treatment, remission in the ketamine group remained high, although nonsignificantly versus placebo (69.5% vs. 56.3%; OR, 0.8; 95% CI, 0.3-2.5; P = .7).

The researchers noted the beneficial effect of ketamine on suicidal ideation could be mediated by an effect on psychological pain.

“Although mental pain does not necessarily lead to suicidal ideas, recent studies suggest that individuals with severe suicidal ideas (notably those with a plan) also have high levels of mental pain. Ketamine might therefore exert its effects through analgesic mechanisms that reduce mental pain,” they wrote.

Ketamine’s side effects were “limited” with no manic or psychotic symptoms seen. The main side effects, including sedation, denationalization/derealization, nausea, and dizziness, were of short duration and occurred in about 10% or fewer patients.

The investigators acknowledged that the nonsignificant effect of ketamine in the patients with major depressive disorders in this study is “challenging to interpret.”

They pointed out the study may have lacked power to detect an effect in these patients. In addition, this group might be particularly heterogeneous, with more patients sensitive to a placebo effect and more patients requiring repeated ketamine infusions.
 

A new perspective on ketamine

In an accompanying editorial, Riccardo De Giorgi, MD, Wellcome Trust doctoral training fellow, department of psychiatry, University of Oxford (England), said the study challenges current thinking about ketamine.

The “unexpected” outcome (no benefit) in the depressive group “perhaps defies the prevailing notion that patients with major depression would benefit most from ketamine,” Dr. De Giorgi wrote.

“In fact, both usual care and ketamine given with usual care led to low, comparable remission rates of 35.7% and 42.3% for suicidal ideation, respectively, in patients with depressive disorder,” Dr. De Giorgi pointed out.

“While this study therefore confirms that many patients with depressive disorder and suicidal ideation remain poorly served by available treatments, it shows that another important group of patients with acute suicidal ideation, those with bipolar disorder, could benefit from ketamine,” Dr. De Giorgi wrote.

“Once again, here is evidence that careful clinical evaluation must precede any consideration of ketamine use, which must be reserved for specific clinical presentations and not given indiscriminately to anyone presenting with suicidal thoughts,” he concluded.

Funding for the study was provided by Programme Hospitalier de Recherche Clinique National. Dr. Jollant and Dr. De Giorgi disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Two illicit drugs are contributing to a sharp rise in fentanyl-related deaths, a new study from the Centers for Disease Control and Prevention shows.

Para-fluorofentanyl, a schedule I substance often found in heroin packets and counterfeit pills, is making a comeback on the illicit drug market, Jordan Trecki, PhD, and associates reported in the Centers for Disease Control and Prevention’s Morbidity and Mortality Weekly Report (2022 Jan 28;71[4]:153-5). U.S. medical examiner reports and national law enforcement seizure data point to a rise in encounters of this drug along with metonitazene, a benzimidazole-opioid, in combination with fentanyl.

On their own, para-fluorofentanyl and metonitazene can kill the user through respiratory depression. Combinations of these substances and other opioids, including fentanyl-related compounds or adulterants, “pose an even greater potential harm to the patient than previously observed,” reported Dr. Trecki, a pharmacologist affiliated with the Drug Enforcement Administration, and colleagues.

Opioids contribute to about 75% of all U.S. drug overdose deaths, which rose by 28.5% during 2020-2021, according to the National Center for Health Statistics. And fentanyl is replacing heroin as the primary drug of use, said addiction specialist Brian Fuehrlein, MD, PhD, in an interview.

“For patients with stimulant use disorder and even cannabis use disorder, fentanyl is becoming more and more common as an adulterant in those substances, often resulting in inadvertent use. Hence, fentanyl and fentanyl-like drugs and fentanyl analogues are becoming increasingly common and important,” said Dr. Fuehrlein, director of the psychiatric emergency room at the VA Connecticut Healthcare System. He was not involved with the MMWR study.
 

Tennessee data reflect national problem

Recent data from a medical examiner in Knoxville, Tenn., illustrate what might be happening nationwide with those two emerging substances.

Over the last 2 years, the Knox County Regional Forensic Center has identified para-fluorofentanyl in the toxicology results of drug overdose victims, and metonitazene – either on its own or in combination with fentanyl and para-fluorofentanyl. Fentanyl appeared in 562 or 73% of 770 unintentional drug overdose deaths from November 2020 to August 2021. Forty-eight of these cases involved para-fluorofentanyl, and 26 involved metonitazene.

“Although the percentage of law enforcement encounters with these substances in Tennessee decreased relative to the national total percentage within this time frame, the increase in encounters both within Tennessee and nationally reflect an increased distribution of para-fluorofentanyl and metonitazene throughout the United States,” the authors reported.
 

How to identify substances, manage overdoses

The authors encouraged physicians, labs, and medical examiners to be on the lookout for these two substances either in the emergency department or when identifying the cause of drug overdose deaths.

They also advised that stronger opioids, such as fentanyl, para-fluorofentanyl, metonitazene, or other benzimidazoles may warrant additional doses of the opioid-reversal drug naloxone.

While he hasn’t personally seen any of these drugs in his practice, “I would assume that these are on the rise due to inexpensive cost to manufacture and potency of effect,” said Dr. Fuehrlein, also an associate professor of psychiatry at Yale University, New Haven, Conn.

The need for additional naloxone to manage acute overdoses is a key takeaway of the MMWR paper, he added. Clinicians should also educate patients about harm reduction strategies to avoid overdose death when using potentially powerful and unknown drugs. “Things like start low and go slow, buy from the same supplier, do not use opioids with alcohol or benzos, have Narcan available, do not use alone, etc.”

Dr. Fuehrlein had no disclosures.

Two illicit drugs are contributing to a sharp rise in fentanyl-related deaths, a new study from the Centers for Disease Control and Prevention shows.

Para-fluorofentanyl, a schedule I substance often found in heroin packets and counterfeit pills, is making a comeback on the illicit drug market, Jordan Trecki, PhD, and associates reported in the Centers for Disease Control and Prevention’s Morbidity and Mortality Weekly Report (2022 Jan 28;71[4]:153-5). U.S. medical examiner reports and national law enforcement seizure data point to a rise in encounters of this drug along with metonitazene, a benzimidazole-opioid, in combination with fentanyl.

On their own, para-fluorofentanyl and metonitazene can kill the user through respiratory depression. Combinations of these substances and other opioids, including fentanyl-related compounds or adulterants, “pose an even greater potential harm to the patient than previously observed,” reported Dr. Trecki, a pharmacologist affiliated with the Drug Enforcement Administration, and colleagues.

Opioids contribute to about 75% of all U.S. drug overdose deaths, which rose by 28.5% during 2020-2021, according to the National Center for Health Statistics. And fentanyl is replacing heroin as the primary drug of use, said addiction specialist Brian Fuehrlein, MD, PhD, in an interview.

“For patients with stimulant use disorder and even cannabis use disorder, fentanyl is becoming more and more common as an adulterant in those substances, often resulting in inadvertent use. Hence, fentanyl and fentanyl-like drugs and fentanyl analogues are becoming increasingly common and important,” said Dr. Fuehrlein, director of the psychiatric emergency room at the VA Connecticut Healthcare System. He was not involved with the MMWR study.
 

Tennessee data reflect national problem

Recent data from a medical examiner in Knoxville, Tenn., illustrate what might be happening nationwide with those two emerging substances.

Over the last 2 years, the Knox County Regional Forensic Center has identified para-fluorofentanyl in the toxicology results of drug overdose victims, and metonitazene – either on its own or in combination with fentanyl and para-fluorofentanyl. Fentanyl appeared in 562 or 73% of 770 unintentional drug overdose deaths from November 2020 to August 2021. Forty-eight of these cases involved para-fluorofentanyl, and 26 involved metonitazene.

“Although the percentage of law enforcement encounters with these substances in Tennessee decreased relative to the national total percentage within this time frame, the increase in encounters both within Tennessee and nationally reflect an increased distribution of para-fluorofentanyl and metonitazene throughout the United States,” the authors reported.
 

How to identify substances, manage overdoses

The authors encouraged physicians, labs, and medical examiners to be on the lookout for these two substances either in the emergency department or when identifying the cause of drug overdose deaths.

They also advised that stronger opioids, such as fentanyl, para-fluorofentanyl, metonitazene, or other benzimidazoles may warrant additional doses of the opioid-reversal drug naloxone.

While he hasn’t personally seen any of these drugs in his practice, “I would assume that these are on the rise due to inexpensive cost to manufacture and potency of effect,” said Dr. Fuehrlein, also an associate professor of psychiatry at Yale University, New Haven, Conn.

The need for additional naloxone to manage acute overdoses is a key takeaway of the MMWR paper, he added. Clinicians should also educate patients about harm reduction strategies to avoid overdose death when using potentially powerful and unknown drugs. “Things like start low and go slow, buy from the same supplier, do not use opioids with alcohol or benzos, have Narcan available, do not use alone, etc.”

Dr. Fuehrlein had no disclosures.

Two illicit drugs are contributing to a sharp rise in fentanyl-related deaths, a new study from the Centers for Disease Control and Prevention shows.

Para-fluorofentanyl, a schedule I substance often found in heroin packets and counterfeit pills, is making a comeback on the illicit drug market, Jordan Trecki, PhD, and associates reported in the Centers for Disease Control and Prevention’s Morbidity and Mortality Weekly Report (2022 Jan 28;71[4]:153-5). U.S. medical examiner reports and national law enforcement seizure data point to a rise in encounters of this drug along with metonitazene, a benzimidazole-opioid, in combination with fentanyl.

On their own, para-fluorofentanyl and metonitazene can kill the user through respiratory depression. Combinations of these substances and other opioids, including fentanyl-related compounds or adulterants, “pose an even greater potential harm to the patient than previously observed,” reported Dr. Trecki, a pharmacologist affiliated with the Drug Enforcement Administration, and colleagues.

Opioids contribute to about 75% of all U.S. drug overdose deaths, which rose by 28.5% during 2020-2021, according to the National Center for Health Statistics. And fentanyl is replacing heroin as the primary drug of use, said addiction specialist Brian Fuehrlein, MD, PhD, in an interview.

“For patients with stimulant use disorder and even cannabis use disorder, fentanyl is becoming more and more common as an adulterant in those substances, often resulting in inadvertent use. Hence, fentanyl and fentanyl-like drugs and fentanyl analogues are becoming increasingly common and important,” said Dr. Fuehrlein, director of the psychiatric emergency room at the VA Connecticut Healthcare System. He was not involved with the MMWR study.
 

Tennessee data reflect national problem

Recent data from a medical examiner in Knoxville, Tenn., illustrate what might be happening nationwide with those two emerging substances.

Over the last 2 years, the Knox County Regional Forensic Center has identified para-fluorofentanyl in the toxicology results of drug overdose victims, and metonitazene – either on its own or in combination with fentanyl and para-fluorofentanyl. Fentanyl appeared in 562 or 73% of 770 unintentional drug overdose deaths from November 2020 to August 2021. Forty-eight of these cases involved para-fluorofentanyl, and 26 involved metonitazene.

“Although the percentage of law enforcement encounters with these substances in Tennessee decreased relative to the national total percentage within this time frame, the increase in encounters both within Tennessee and nationally reflect an increased distribution of para-fluorofentanyl and metonitazene throughout the United States,” the authors reported.
 

How to identify substances, manage overdoses

The authors encouraged physicians, labs, and medical examiners to be on the lookout for these two substances either in the emergency department or when identifying the cause of drug overdose deaths.

They also advised that stronger opioids, such as fentanyl, para-fluorofentanyl, metonitazene, or other benzimidazoles may warrant additional doses of the opioid-reversal drug naloxone.

While he hasn’t personally seen any of these drugs in his practice, “I would assume that these are on the rise due to inexpensive cost to manufacture and potency of effect,” said Dr. Fuehrlein, also an associate professor of psychiatry at Yale University, New Haven, Conn.

The need for additional naloxone to manage acute overdoses is a key takeaway of the MMWR paper, he added. Clinicians should also educate patients about harm reduction strategies to avoid overdose death when using potentially powerful and unknown drugs. “Things like start low and go slow, buy from the same supplier, do not use opioids with alcohol or benzos, have Narcan available, do not use alone, etc.”

Dr. Fuehrlein had no disclosures.

Intranasal oxytocin (INOT) is showing early promise as a treatment for cocaine dependence, new research suggests.

Results of a small 6-week randomized, placebo-controlled trial in patients with cocaine use disorder showed a high level of abstinence in those who received INOT beginning 2 weeks after treatment initiation.

“In this population of cocaine-dependent individuals in a community clinic setting, we found the use of intranasal oxytocin to be safe and feasible, with no adverse events, and a high level of abstinence after 6 weeks, compared to placebo,” lead author Wilfrid Noel Raby, PhD, MD, a Teaneck, N.J.–based psychiatrist, said in an interview.

On the other hand, “the findings were paradoxical because there was a greater dropout rate in the intranasal oxytocin group after week 1, suggesting that oxytocin might have a biphasic effect, which should be addressed in future studies,” added Dr. Raby, who was an adjunct clinical professor of psychiatry, division on substance abuse, Montefiore Medical Center, Albert Einstein College of Medicine, New York, when the trial was conducted.

The study was published in the March issue of Drug and Alcohol Dependence Reports.
 

‘Crying need’

“Focus on stress reactivity in addiction and on the loss of social norms among drug users has generated interest in oxytocin, due to its purported role in these traits and regulation of stress,” the authors wrote.

Oxytocin is a neuropeptide that regulates autonomic functions. Previous research in cannabis users suggests it may have a role in treating addiction by reportedly reducing cravings. In addition, earlier research also suggests it cuts stress reactivity and state anger in cocaine users.

A previous trial of INOT showed it decreased cocaine craving, and additional research has revealed recurrent cocaine use results in lower endogenous oxytocin levels and depleted oxytocin in the hypothalamus and amygdala.

“The bias of my work is to look for simple, nonaddictive medicinal approaches that can be used in the community settings, because that’s where the greatest crying need lies and where most problems from drug addiction occur,” said Dr. Raby.

“There has been long-standing interest in how the brain adaptive systems, or so-called ‘stress systems,’ adjust in the face of drug dependence in general, and the main focus of the study has been to understand this response and use the insight from these adaptations to develop medicinal treatments for drug abuse, particularly cocaine dependence,” he added.

To investigate the potential for INOT to promote abstinence from cocaine, the researchers randomized 26 patients with cocaine use disorder (73% male, mean [SD] age, 50.2 [5.4] years). Most participants had been using cocaine on a regular basis for about 25 years, and baseline average days of cocaine use was 11.1 (5.7) during the 30 days prior to study entry.

At a baseline, the researchers collected participants’ medical history and conducted a physical examination, urine toxicology, electrocardiogram, comprehensive metabolic panel, and complete blood count. They used the MINI International Neuropsychiatric Interview to confirm the diagnosis of cocaine dependence.

The study began with a 7-day inpatient abstinence induction stage, after which participants were randomized to receive either INOT 24 IU or intranasal placebo (n = 15 and n = 11, respectively).

Patients attended the clinic three times per week. At each visit, they completed the cocaine craving scale, the Perceived Stress Scale, and the Clinician Global Inventory (all self-reports), as well as the Time Line Follow Back (TLFB) to document cocaine use.

Participants were trained to self-administer an intranasal solution at home, with compliance monitored in two ways – staff observed self-administration of the randomized medication at the time of clinic visits and weighed the “at home bottle.”

Cocaine use was determined via urine toxicology and TLFB self-report.
 

Threshold period

INOT did not induce ≥ 3 weeks of continuous abstinence. However, beginning with week 3, the odds of weekly abstinence increased dramatically in the INOT group, from 4.61 (95% confidence interval,1.05, 20.3) to 15.0 (1.18, 190.2) by week 6 (t = 2.12, P = .037).

The overall medication group by time interaction across all 6 weeks was not significant (F1,69 = 1.73, P = .19); but when the interaction was removed, the difference between the overall effect of medication (INOT vs. placebo) over all 6 weeks “reached trend-level significance” (F1,70) = 3.42, P = .07).

The subjective rating outcomes (cravings, perceived stress, cocaine dependence, and depression) “did not show a significant medication group by time interaction effect,” the authors reported, although stress-induced cravings did tend toward a significant difference between the groups.

Half of the patients did not complete the full 6 weeks. Of those who discontinued, 85% came from the INOT group and 15% from the placebo group. Of the 11 who dropped out from the treatment group, seven were abstinent at the time of discontinuation for ≥ 1 week.

There were no significant differences in rates of reported side effects between the two groups.

“This study highlights some promise that perhaps there is a threshold period of time you need to cross, after which time oxytocin could really be really helpful as acute or maintenance medication,” said Dr. Raby. The short study duration might have been a disadvantage. “We might have seen better results if the study had been 8 or 12 weeks in duration.”

Using motivational approaches during the early phase – e.g., psychotherapy or a voucher system – might increase adherence, and then “after this initial lag, we might see a more therapeutic effect,” he suggested.

Dr. Raby noted that his group studied stress hormone secretions in the cocaine-dependent study participants during the 7-day induction period and that the findings, when published, could shed light on this latency period. “Cocaine dependence creates adaptations in the stress system,” he said.
 

‘Nice first step’

Commenting on the study, Jane Joseph, PhD, professor in the department of neurosciences and director of the neuroimaging division at Medical University of South Carolina, Charleston, said it is “nice to see a clinical trial using oxytocin in cocaine dependence [because] preclinical research has shown fairly convincing effects of oxytocin in reducing craving or stress in the context of cocaine seeking, but findings are rather mixed in human studies.”

Dr. Joseph, who was not involved with the study, said her group’s research showed oxytocin to be the most helpful for men with cocaine use disorder who reported childhood trauma, while for women, oxytocin “seemed to worsen their reactivity to cocaine cues.”

She said the current study is a “nice first step” and suggested that future research should include larger sample sizes to “address some of the individual variability in the response to oxytocin by examining sex differences or trauma history.”

The study was supported by an award from the National Institute of Drug Abuse. Dr. Raby and coauthors and Dr. Joseph have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Intranasal oxytocin (INOT) is showing early promise as a treatment for cocaine dependence, new research suggests.

Results of a small 6-week randomized, placebo-controlled trial in patients with cocaine use disorder showed a high level of abstinence in those who received INOT beginning 2 weeks after treatment initiation.

“In this population of cocaine-dependent individuals in a community clinic setting, we found the use of intranasal oxytocin to be safe and feasible, with no adverse events, and a high level of abstinence after 6 weeks, compared to placebo,” lead author Wilfrid Noel Raby, PhD, MD, a Teaneck, N.J.–based psychiatrist, said in an interview.

On the other hand, “the findings were paradoxical because there was a greater dropout rate in the intranasal oxytocin group after week 1, suggesting that oxytocin might have a biphasic effect, which should be addressed in future studies,” added Dr. Raby, who was an adjunct clinical professor of psychiatry, division on substance abuse, Montefiore Medical Center, Albert Einstein College of Medicine, New York, when the trial was conducted.

The study was published in the March issue of Drug and Alcohol Dependence Reports.
 

‘Crying need’

“Focus on stress reactivity in addiction and on the loss of social norms among drug users has generated interest in oxytocin, due to its purported role in these traits and regulation of stress,” the authors wrote.

Oxytocin is a neuropeptide that regulates autonomic functions. Previous research in cannabis users suggests it may have a role in treating addiction by reportedly reducing cravings. In addition, earlier research also suggests it cuts stress reactivity and state anger in cocaine users.

A previous trial of INOT showed it decreased cocaine craving, and additional research has revealed recurrent cocaine use results in lower endogenous oxytocin levels and depleted oxytocin in the hypothalamus and amygdala.

“The bias of my work is to look for simple, nonaddictive medicinal approaches that can be used in the community settings, because that’s where the greatest crying need lies and where most problems from drug addiction occur,” said Dr. Raby.

“There has been long-standing interest in how the brain adaptive systems, or so-called ‘stress systems,’ adjust in the face of drug dependence in general, and the main focus of the study has been to understand this response and use the insight from these adaptations to develop medicinal treatments for drug abuse, particularly cocaine dependence,” he added.

To investigate the potential for INOT to promote abstinence from cocaine, the researchers randomized 26 patients with cocaine use disorder (73% male, mean [SD] age, 50.2 [5.4] years). Most participants had been using cocaine on a regular basis for about 25 years, and baseline average days of cocaine use was 11.1 (5.7) during the 30 days prior to study entry.

At a baseline, the researchers collected participants’ medical history and conducted a physical examination, urine toxicology, electrocardiogram, comprehensive metabolic panel, and complete blood count. They used the MINI International Neuropsychiatric Interview to confirm the diagnosis of cocaine dependence.

The study began with a 7-day inpatient abstinence induction stage, after which participants were randomized to receive either INOT 24 IU or intranasal placebo (n = 15 and n = 11, respectively).

Patients attended the clinic three times per week. At each visit, they completed the cocaine craving scale, the Perceived Stress Scale, and the Clinician Global Inventory (all self-reports), as well as the Time Line Follow Back (TLFB) to document cocaine use.

Participants were trained to self-administer an intranasal solution at home, with compliance monitored in two ways – staff observed self-administration of the randomized medication at the time of clinic visits and weighed the “at home bottle.”

Cocaine use was determined via urine toxicology and TLFB self-report.
 

Threshold period

INOT did not induce ≥ 3 weeks of continuous abstinence. However, beginning with week 3, the odds of weekly abstinence increased dramatically in the INOT group, from 4.61 (95% confidence interval,1.05, 20.3) to 15.0 (1.18, 190.2) by week 6 (t = 2.12, P = .037).

The overall medication group by time interaction across all 6 weeks was not significant (F1,69 = 1.73, P = .19); but when the interaction was removed, the difference between the overall effect of medication (INOT vs. placebo) over all 6 weeks “reached trend-level significance” (F1,70) = 3.42, P = .07).

The subjective rating outcomes (cravings, perceived stress, cocaine dependence, and depression) “did not show a significant medication group by time interaction effect,” the authors reported, although stress-induced cravings did tend toward a significant difference between the groups.

Half of the patients did not complete the full 6 weeks. Of those who discontinued, 85% came from the INOT group and 15% from the placebo group. Of the 11 who dropped out from the treatment group, seven were abstinent at the time of discontinuation for ≥ 1 week.

There were no significant differences in rates of reported side effects between the two groups.

“This study highlights some promise that perhaps there is a threshold period of time you need to cross, after which time oxytocin could really be really helpful as acute or maintenance medication,” said Dr. Raby. The short study duration might have been a disadvantage. “We might have seen better results if the study had been 8 or 12 weeks in duration.”

Using motivational approaches during the early phase – e.g., psychotherapy or a voucher system – might increase adherence, and then “after this initial lag, we might see a more therapeutic effect,” he suggested.

Dr. Raby noted that his group studied stress hormone secretions in the cocaine-dependent study participants during the 7-day induction period and that the findings, when published, could shed light on this latency period. “Cocaine dependence creates adaptations in the stress system,” he said.
 

‘Nice first step’

Commenting on the study, Jane Joseph, PhD, professor in the department of neurosciences and director of the neuroimaging division at Medical University of South Carolina, Charleston, said it is “nice to see a clinical trial using oxytocin in cocaine dependence [because] preclinical research has shown fairly convincing effects of oxytocin in reducing craving or stress in the context of cocaine seeking, but findings are rather mixed in human studies.”

Dr. Joseph, who was not involved with the study, said her group’s research showed oxytocin to be the most helpful for men with cocaine use disorder who reported childhood trauma, while for women, oxytocin “seemed to worsen their reactivity to cocaine cues.”

She said the current study is a “nice first step” and suggested that future research should include larger sample sizes to “address some of the individual variability in the response to oxytocin by examining sex differences or trauma history.”

The study was supported by an award from the National Institute of Drug Abuse. Dr. Raby and coauthors and Dr. Joseph have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Intranasal oxytocin (INOT) is showing early promise as a treatment for cocaine dependence, new research suggests.

Results of a small 6-week randomized, placebo-controlled trial in patients with cocaine use disorder showed a high level of abstinence in those who received INOT beginning 2 weeks after treatment initiation.

“In this population of cocaine-dependent individuals in a community clinic setting, we found the use of intranasal oxytocin to be safe and feasible, with no adverse events, and a high level of abstinence after 6 weeks, compared to placebo,” lead author Wilfrid Noel Raby, PhD, MD, a Teaneck, N.J.–based psychiatrist, said in an interview.

On the other hand, “the findings were paradoxical because there was a greater dropout rate in the intranasal oxytocin group after week 1, suggesting that oxytocin might have a biphasic effect, which should be addressed in future studies,” added Dr. Raby, who was an adjunct clinical professor of psychiatry, division on substance abuse, Montefiore Medical Center, Albert Einstein College of Medicine, New York, when the trial was conducted.

The study was published in the March issue of Drug and Alcohol Dependence Reports.
 

‘Crying need’

“Focus on stress reactivity in addiction and on the loss of social norms among drug users has generated interest in oxytocin, due to its purported role in these traits and regulation of stress,” the authors wrote.

Oxytocin is a neuropeptide that regulates autonomic functions. Previous research in cannabis users suggests it may have a role in treating addiction by reportedly reducing cravings. In addition, earlier research also suggests it cuts stress reactivity and state anger in cocaine users.

A previous trial of INOT showed it decreased cocaine craving, and additional research has revealed recurrent cocaine use results in lower endogenous oxytocin levels and depleted oxytocin in the hypothalamus and amygdala.

“The bias of my work is to look for simple, nonaddictive medicinal approaches that can be used in the community settings, because that’s where the greatest crying need lies and where most problems from drug addiction occur,” said Dr. Raby.

“There has been long-standing interest in how the brain adaptive systems, or so-called ‘stress systems,’ adjust in the face of drug dependence in general, and the main focus of the study has been to understand this response and use the insight from these adaptations to develop medicinal treatments for drug abuse, particularly cocaine dependence,” he added.

To investigate the potential for INOT to promote abstinence from cocaine, the researchers randomized 26 patients with cocaine use disorder (73% male, mean [SD] age, 50.2 [5.4] years). Most participants had been using cocaine on a regular basis for about 25 years, and baseline average days of cocaine use was 11.1 (5.7) during the 30 days prior to study entry.

At a baseline, the researchers collected participants’ medical history and conducted a physical examination, urine toxicology, electrocardiogram, comprehensive metabolic panel, and complete blood count. They used the MINI International Neuropsychiatric Interview to confirm the diagnosis of cocaine dependence.

The study began with a 7-day inpatient abstinence induction stage, after which participants were randomized to receive either INOT 24 IU or intranasal placebo (n = 15 and n = 11, respectively).

Patients attended the clinic three times per week. At each visit, they completed the cocaine craving scale, the Perceived Stress Scale, and the Clinician Global Inventory (all self-reports), as well as the Time Line Follow Back (TLFB) to document cocaine use.

Participants were trained to self-administer an intranasal solution at home, with compliance monitored in two ways – staff observed self-administration of the randomized medication at the time of clinic visits and weighed the “at home bottle.”

Cocaine use was determined via urine toxicology and TLFB self-report.
 

Threshold period

INOT did not induce ≥ 3 weeks of continuous abstinence. However, beginning with week 3, the odds of weekly abstinence increased dramatically in the INOT group, from 4.61 (95% confidence interval,1.05, 20.3) to 15.0 (1.18, 190.2) by week 6 (t = 2.12, P = .037).

The overall medication group by time interaction across all 6 weeks was not significant (F1,69 = 1.73, P = .19); but when the interaction was removed, the difference between the overall effect of medication (INOT vs. placebo) over all 6 weeks “reached trend-level significance” (F1,70) = 3.42, P = .07).

The subjective rating outcomes (cravings, perceived stress, cocaine dependence, and depression) “did not show a significant medication group by time interaction effect,” the authors reported, although stress-induced cravings did tend toward a significant difference between the groups.

Half of the patients did not complete the full 6 weeks. Of those who discontinued, 85% came from the INOT group and 15% from the placebo group. Of the 11 who dropped out from the treatment group, seven were abstinent at the time of discontinuation for ≥ 1 week.

There were no significant differences in rates of reported side effects between the two groups.

“This study highlights some promise that perhaps there is a threshold period of time you need to cross, after which time oxytocin could really be really helpful as acute or maintenance medication,” said Dr. Raby. The short study duration might have been a disadvantage. “We might have seen better results if the study had been 8 or 12 weeks in duration.”

Using motivational approaches during the early phase – e.g., psychotherapy or a voucher system – might increase adherence, and then “after this initial lag, we might see a more therapeutic effect,” he suggested.

Dr. Raby noted that his group studied stress hormone secretions in the cocaine-dependent study participants during the 7-day induction period and that the findings, when published, could shed light on this latency period. “Cocaine dependence creates adaptations in the stress system,” he said.
 

‘Nice first step’

Commenting on the study, Jane Joseph, PhD, professor in the department of neurosciences and director of the neuroimaging division at Medical University of South Carolina, Charleston, said it is “nice to see a clinical trial using oxytocin in cocaine dependence [because] preclinical research has shown fairly convincing effects of oxytocin in reducing craving or stress in the context of cocaine seeking, but findings are rather mixed in human studies.”

Dr. Joseph, who was not involved with the study, said her group’s research showed oxytocin to be the most helpful for men with cocaine use disorder who reported childhood trauma, while for women, oxytocin “seemed to worsen their reactivity to cocaine cues.”

She said the current study is a “nice first step” and suggested that future research should include larger sample sizes to “address some of the individual variability in the response to oxytocin by examining sex differences or trauma history.”

The study was supported by an award from the National Institute of Drug Abuse. Dr. Raby and coauthors and Dr. Joseph have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.