Behavioral Assessments of Kindergarteners May Predict Future Earnings, Study Suggests

Behavioral assessments of children at a young age may offer clues about their employment earnings in adulthood, according to a study in JAMA Psychiatry. Specifically, the study found that higher teacher ratings of inattention and aggression-opposition in kindergarten boys and inattention in kindergarten girls seemed to be associated with lower future earnings after controlling for child IQ and family adversity.

“This study adds to a growing body of literature showing that childhood inattention, antisocial behavior, and low levels of prosociality act as channels for adverse social and economic outcomes in adulthood,” wrote Francis Vergunst, D.Phil., of the University of Montreal and colleagues. “Early monitoring and support for children exhibiting high inattention, aggression-opposition, and low levels of prosocial behaviors could have long-term socioeconomic advantages for those individuals and society.”

The findings were based on data obtained from the Quebec Longitudinal Study of Kindergarten Children—a population-based sample of boys and girls born in 1980 or 1981 in Quebec, Canada, who were followed up through December 2015. As part of the longitudinal study, kindergarten teachers used the Social Behavior Questionnaire to rate students on a three-point scale (0, never true; 1, sometimes or somewhat true; 2, often true) on the following behaviors: anxiety, hyperactivity, inattention, opposition (for example, disobeying and blaming others), physical aggression, and prosociality (for example, helping and showing sympathy toward others). Vergunst and colleagues evaluated the associations between the teacher ratings and reported annual earnings on income tax returns of those same participants at age 33 to 35 years.

The study included 2,850 participants, with a mean age of 35.9 years, of whom 1,470 (51.6%) were male and 2,740 (96.2%) were white. The mean personal earnings at follow-up were U.S. $33,300 for men and $19,400 for women. Higher child IQ was associated with higher earnings, and greater family adversity during childhood was associated with lower earnings for both male and female participants.

A 1-unit increase in inattention score at age 6 years was associated with a decrease in annual earnings of $1,271.49 for male participants and $924.25 for female participants, after the authors adjusted for childhood IQ and family adversity. A combined aggression-opposition score was associated with a reduction in earnings of $699.83 for male participants only, and a 1-unit increase in prosociality score was associated with an increase in earnings of $476.75 for male participants only.

Vergunst and colleagues concluded, “Screening [of children] should begin in kindergarten, in which population-wide assessment is feasible, teachers have a sense of normative social behavior, and teachers’ ratings of children’s behaviors have good predictive validity across a range of outcomes.”

For related information, see the Psychiatric News article “Prospective Study Delves Deeper Into Mental Health Effects of Childhood Trauma.”

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Some Antidepressants May Diminish Pain Control With Tramadol

The effectiveness of tramadol, a frequently prescribed opiate painkiller, may be significantly diminished when patients are also taking certain, commonly prescribed antidepressants, such as bupropion (Wellbutrin), fluoxetine (Prozac), or paroxetine (Paxil), according to a study in Pharmacotherapy.

Those, and other, antidepressants inhibit an enzyme known as CYP2D6, which also metabolizes tramadol. The study found that when CYP2D6 is inhibited by an antidepressant, the painkiller becomes less effective, requiring patients to need a short-acting opiate, such as morphine or another painkiller, to control “breakthrough” pain, the acute pain that breaks through the effects of tramadol. (There are five “strong CYP2D6 inhibitors”: bupropion, fluoxetine, paroxetine, terbinafine, and quinidine. Frost and colleagues list 13 other antidepressants as moderate or weak inhibitors.)

“These findings imply that additional considerations may be required for the evaluation of pain management regimens in patients taking one of these [antidepressant] medications, as higher doses or different [pain-control] agents may be required,” wrote Derek A. Frost, Pharm.D., of University Hospitals Portage Medical Center, Ravenna, Ohio, and colleagues.

They assessed 152 hospitalized patients prescribed tramadol for chronic pain. Of these, 76 were also taking one of the strong CYP2D6-inhibiting antidepressants. The primary outcome measure was the amount of breakthrough opiate required by patients.

Patients receiving one of the antidepressants and tramadol required a higher per-day average of breakthrough opiate (18.2 mg) than those in the control group (5.7 mg) and required more total breakthrough opiate overall (42.4 mg vs 10.2 mg).

“This study supports the use of a tramadol alternative for pain management in patients taking a strong CYP2D6 inhibitor,” the authors wrote. “It would also benefit each patient to assess the response to their depression treatment when a pain management regimen is being considered. Patients who are nonresponsive to treatment while taking a strong CYP2D6 inhibitor may be switched to an appropriate alternative regimen for managing their depression.”

For related information see the Psychiatric News article, “NIDA Director Outlines Institute’s Efforts to Understand Pain, Reduce Opioid Misuse.”

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Researchers Identify Factors That May Predict CBT Response in Youth With OCD

The extent to which youth with obsessive-compulsive disorder (OCD) avoid situations that trigger distress and compulsions and recognize their symptoms may predict how likely they are to respond to cognitive-behavioral therapy (CBT), reports a study in the Journal of the American Academy of Child & Adolescent Psychiatry.

“[E]xtensive avoidance may mask a youth’s symptom severity at baseline … and prevent, or slow, youth’s engagement in [treatment],” wrote Robert R. Selles, Ph.D., of the University of British Columbia and colleagues. The findings point to the importance of accurately assessing these factors in youth with OCD before starting treatment and monitoring changes throughout therapy.

CBT that emphasizes exposure and response prevention—encouraging a patient to face thoughts, objects, and situations that trigger obsessions while not engaging in compulsive behavior—is a first-line approach to treating pediatric patients with OCD. To examine factors that may predict how youth with OCD respond to CBT, Selles and colleagues analyzed aggregated data from CBT trials involving 573 youth aged 7 to 19 who had been diagnosed with OCD.

As part of these trials, participants answered questions about avoidance behaviors (for example, how often they avoided doing things, going places, or being with people because of obsessions or compulsions) and insight (for example, if they believed their behaviors were reasonable) before and after receiving CBT. Participants also answered questions about the impact of OCD symptoms on daily activities; these responses were then compared with those given by their parents.

Selles and colleagues found that insight among youth before receiving CBT was not significantly related to response to CBT (defined as ≥35% reduction in Children’s Yale Brown Obsessive-Compulsive Scale score). In contrast, greater baseline avoidance and limited child recognition of impairment predicted reduced likelihood of achieving response to CBT. “Response rates steadily declined with worsening avoidance from a 71.9% (n = 69) response rate for youth with no avoidance down to a 48.3% (n = 14) response rate for youth with extreme avoidance,” they wrote. “Only 46.2% (n = 30) of youth with limited recognition of impairment (relative to the parent’s recognition) responded to treatment, in comparison to 62.3% to 66.8% of youth with either concordant or limited parent impairment recognition.” Insight and avoidance substantially improved with CBT.

“[A]voidance, insight, and parent-child concordance on impairment all appear to be variables relevant to CBT. As a result, it is recommended that clinicians assess and monitor these factors prior to and throughout treatment,” Selles and colleagues concluded. “[T]he use of more comprehensive and frequent assessment of these domains throughout the treatment process is recommended to identify reasons for lack of change in or worsening of insight and/or avoidance over treatment.”

For related information, see the Psychiatric News article “Report Highlights Alternative Treatment Options for OCD.”

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FDA Approves Medication to Treat Female Sexual Disorder

The Food and Drug Administration (FDA) on Friday approved Vyleesi (bremelanotide) to treat premenopausal women for acquired, generalized hypoactive sexual desire disorder (HSDD). HSDD (classified as female sexual interest/arousal disorder in DSM-5) is characterized by low sexual desire that causes distress and cannot be explained by a comorbid physical or psychiatric illness, the side effects of substance use or medications, or severe relationship problems. Acquired HSDD means a woman has previously experienced sexual desire (it has not been a lifelong problem).

“There are women who, for no known reason, have reduced sexual desire that causes marked distress and who can benefit from safe and effective pharmacologic treatment,” said Hylton V. Joffe, M.D., M.M.Sc., director of the FDA’s Division of Bone, Reproductive, and Urologic Products in the agency press release. “As part of the FDA’s commitment to protect and advance the health of women, we’ll continue to support the development of safe and effective treatments for female sexual dysfunction.”

The approval of Vyleesi was supported by two 24-week, randomized clinical studies involving 1,247 premenopausal women with HSDD. In both trials, Vyleesi was more effective than placebo at improving patient-reported sexual desire and reducing emotional distress. Vyleesi is not approved to enhance sexual performance, and women should not use more than one dose every 24 hours or more than eight doses per month, according to the FDA statement.

The most common side effects of Vyleesi are headache, nausea, skin flushing, and reactions at the injection site. The medication can temporarily increase blood pressure, so it should not be taken by women with uncontrolled hypertension or those at high risk of cardiovascular disease. Vyleesi should also not be taken by women taking oral naltrexone (used to treat alcohol use disorder and opioid use disorder), as this medication interferes with naltrexone activity.

To achieve the desired effects of Vyleesi, women are advised to inject the medication into their abdomen or thigh at least 45 minutes before anticipated sexual activity. The medication is known to activate receptors for the hormone melanocortin, but the mechanism by which it improves sexual desire and reduces related distress is unknown.

As noted in a statement by AMAG Pharmaceuticals, manufacturer of Vyleesi, the medication is not indicated for treatment of HSDD in men and postmenopausal women. The medication will be commercially available in September at select pharmacies.

For related information, see the Psychiatric News article “Experts Continue to Debate if Addyi Benefits Outweigh Risks.”

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Long Daytime Naps Linked to Increased Cognitive Decline in Older Men

A study in Alzheimer’s & Dementia suggests that older men who sleep more than two hours during the day could have a higher risk of developing cognitive decline.

“While sleep is considered to enhance memory retention and consolidation, especially among healthy younger adults, it remains controversial whether napping could benefit cognition by compensating for poor nighttime sleep, or if napping might be a … risk factor of cognitive impairment in the elderly,” wrote Yue Leng, Ph.D., M.Phil., of the University of California, San Francisco, and colleagues.

Leng and colleagues measured naps in 2,751 men aged 65 years and older who were enrolled in the Osteoporotic Fractures in Men Study between 2000 and 2002. The participants wore devices similar to wristwatches that measured sleep-wake activity for at least five days in a row when they first enrolled in the study, then had at least one follow-up visit over the next 12 years in which researchers measured their cognitive function.

The researchers found that men who napped for at least two hours during the day at baseline were 66% more likely to develop cognitive impairment than those who napped for fewer than 30 minutes. When the researchers included data on how well and how long the participants slept at night, they found that the so-called “long nappers” who also slept soundly or for six to eight hours a night had roughly twice the risk of developing cognitive impairment compared with their counterparts whose naps were shorter than 30 minutes. However, longer naps were not associated with a higher risk of cognitive decline among participants who did not sleep well at night or who only slept a few hours a night.

“This indicates that the effects of napping on cognition are different among those who sleep poorly and those who sleep well at night,” Leng and colleagues wrote. “Napping might help compensate for poor nighttime sleep and thus provide extra benefits on cognition among those who sleep poorly at night. Meanwhile, it is unclear why napping might be associated with increased risk of cognitive impairment among those who sleep well at night.”

Because the study included only men and most participants were white, the researchers cautioned the findings may not be generalizable to women and/or people of other ethnicities. They concluded that excessive napping could be either an early sign or a risk factor of cognitive decline, and they encouraged health professionals to pay attention to 24-hour sleep-wake cycles of older patients.

For related information, see the Psychiatric News article “Sleep Loss Found to Exacerbate Spread of Toxic Protein Associated With Alzheimer’s Disease.”

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Chronic Physical Conditions in Youth May Raise Risk for Mental Health Conditions

Young people with chronic physical conditions such as asthma or diabetes are more likely to be at risk for later mental health conditions, according to a report released this month in Pediatrics.

Moreover, the limitations that young people may experience because of their chronic physical conditions appear to contribute to their risk for mental health problems, said John Adams, M.D., and colleagues in the Department of Pediatrics at the Cambridge Health Alliance.

“[P]rograms and policies designed to improve care of youth with chronic physical conditions should identify opportunities to … modify the physical or social environment" so young people can “fully participate in activities important to their developmental progress,” they wrote.

Adams and colleagues analyzed data from the Medical Expenditure Panel Survey (MEPS) from 2003 to 2014 on 48,572 youth aged 6 to 25 years. MEPS, a nationally representative survey of the U.S. population conducted by the Agency for Healthcare Research and Quality, asks respondents open-ended questions about health problems and medical encounters that occurred during the reporting period.

MEPS also asks participants if they are limited in their ability to “work at a job, do housework, or go to school” or “participate in social, recreational, or family activities” because of an “impairment or a physical or mental health problem.”

The researchers calculated the two-year cumulative incidence of mental health conditions overall according to whether individuals had a chronic physical condition at baseline. They also looked at whether young people limited their activities due to the physical condition.

Among youth with a physical condition at baseline, 11.5% developed a mental health condition in the next two years compared with 7.1% of youth without a chronic physical condition at baseline. Moreover, youth with baseline physical conditions were three times more likely to report activity limitations, and these youth had a 3.6-times greater risk of a mental health condition.

They calculated that limitations on activity explained 13.5% of the relationship between current physical conditions and subsequent mental health conditions, the researchers stated.

“[S]uch limitations could reduce opportunities for protective exposures or lead to specific harms to mental health such as through decreased educational achievement, increased social stigma, or diminished social well-being,” the researchers said. And these effects may be especially important during adolescence and early adulthood “when gaining autonomy, forming identity, and developing positive relationships are predominant developmental tasks.”

For related information see the Psychiatric News article “Teens With Depression Benefit From Collaborative Care Model.”

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More Pregnant Women Using Cannabis, Possibly Raising Risk of Preterm Birth, Research Shows

It’s becoming more common for pregnant women in the United States to use cannabis: Between 2002 and 2017, the prevalence of past-month cannabis use increased from 3.4% to 7.0% among pregnant women overall and from 5.7% to 12.1% during the first trimester, according to a report published today in JAMA.

These and other findings, which were based on the responses of women to the National Survey on Drug Use and Health (NSDUH), highlight “the importance of screening and interventions for cannabis use among all pregnant women,” wrote Nora Volkow, M.D., director of the National Institute on Drug Abuse, and colleagues.

As part of the NSDUH, interviewers asked women about their pregnancy status; whether they used cannabis in past month; and, if so, how often they used cannabis over the past month (daily/near daily use was defined as 20 or more days of use in the past month). Beginning in 2013, respondents reporting past-year and past-month cannabis use were also asked whether any of their cannabis use was recommended by a health care professional. Those who responded no were categorized as having “nonmedical-only cannabis use.”

Volkow and colleagues analyzed data collected from 467,100 respondents overall between 2002 and 2017. During this time, the adjusted prevalence of past-month daily/near daily cannabis use increased from 0.9% to 3.4% among pregnant women overall, including from 1.8% to 5.3% during the first trimester, from 0.6% to 2.5% during the second trimester, and from 0.5% to 2.5% during the third trimester. Most women reported their cannabis use was not recommended by a health care professional: The prevalence of past-month medical cannabis use among pregnant women aged 12 to 44 years was no more than 0.68%, the authors reported.

In a separate study, also published today in JAMA, researchers reported that women who use cannabis during pregnancy may be more likely to deliver babies preterm.

Daniel J. Corsi, Ph.D., of Ottawa Hospital Research Institute and colleagues examined data collected from 661,617 women aged 15 and older who delivered a baby in an Ontario hospital between April 2012 and December 2017. Corsi and colleagues compared information on birth outcomes of 5,639 mothers who reported use of cannabis during pregnancy with 92,873 mothers who reported no use of cannabis.

After adjustment for confounding variables, Corsi and colleagues found that there was a significant association between reported cannabis use in pregnancy and preterm birth, defined by the authors as less than 37 weeks of gestation. In contrast, there was a statistically significant protective association between reported cannabis exposure and preeclampsia and gestational diabetes, the authors observed.

“These two studies send a straightforward message: cannabis use in pregnancy is likely unsafe; with an increasing prevalence of use (presumably related to growing social acceptability and legalization in many states), its potential for harm may represent a public health problem,” Michael Silverstein, M.D., M.P.H., of Boston Medical Center and colleagues wrote in an accompanying editorial.

For related information, see the Psychiatric Services article “Thinking Carefully About Marijuana Legalization: Public Health Considerations for State Policy Makers.”

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Smoking Increases Risk of Recurrent Suicide Attempts in Patients With Bipolar Disorder, Study Finds

People with bipolar disorder who smoke tobacco are more likely to have recurrent suicide attempts, according to a study in the Journal of Affective Disorders. This risk of recurrent suicide attempts was higher among smokers who also had alcohol use disorder or cannabis use disorder.

The study by Romain Icick, M.D., of Paris Diderot University and colleagues included 916 patients who had bipolar I or II according to DSM-IV criteria and were from France or Norway. Of these participants, 338 (37%) reported at least one suicide attempt, and 173 reported recurrent suicide attempts—defined by authors as two or more suicide attempts.

Icick and colleagues found that patients with bipolar disorder who smoked tobacco daily were 1.75 times as likely to have a history of recurrent suicides compared with nonsmokers with bipolar disorder. Bipolar patients who smoked tobacco and had cannabis use disorder were 2.65 times as likely to have recurrent suicide attempts as nonsmokers with bipolar disorder, while those who smoked tobacco and had alcohol use disorder were 3.58 times as likely. The available data from patients regarding their smoking history suggested these risks were found only in current smokers and not former smokers.

The investigators also found that bipolar patients who experienced depression (as opposed to mania) as their first symptom or who were women were more likely to have recurrent suicide attempts. These risk factors were independent of smoking status, suggesting they could be used to further stratify patients based on their suicide risk.

Icick and colleagues cautioned that this study used retrospective data that included information from patient self-reports. Therefore, it’s possible that some of the substance use occurred following a suicide attempt so the issue of causality cannot be confirmed, they noted. “It is noticeable, however, that emerging data suggest such a causal relationship between smoking outcomes and both mood states and suicide risk,” Icick and colleagues wrote.

For related information, see the Psychiatric Services article “Low-Burden Strategies to Promote Smoking Cessation Treatment Among Patients With Serious Mental Illness.”

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Drugs, Suicide Among Leading Causes of Postpartum Death in California, Study Finds

Drug-related deaths are second only to deaths from obstetric complications among women in California who die within a year of giving birth, a study in the American Journal of Obstetrics and Gynecology has found. Suicide ranked seventh as a cause of death in this population.

Sidra Goldman-Mellor, Ph.D., of the University of California, Merced, and Claire E. Margerison, Ph.D., of Michigan State University analyzed the health records of more than 1 million women who delivered a living infant in California hospitals between 2010 and 2012. They found that in that period, 300 women died within a year of giving birth and that drug-related causes and suicide together were responsible for roughly 1 in 6 of those deaths. Other causes of death in the women included circulatory system disease, cancer, other unintentional injuries, and homicide.

Three-fourths of the women who died from drug-related causes or suicide had visited an emergency department (ED) or hospital at least once between giving birth and dying—a finding that suggests an opportunity for screening, Goldman-Mellor and Margerison wrote.

“This observation suggests that ED and hospital visits may serve as a point of identification of—and eventually, intervention [for]—women at risk for postpartum death. Although examining details of these visits was beyond the scope of this study, this finding warrants further exploration in other samples, including examining the nature of these interactions to identify predictors of maternal death and/or points of intervention,” they wrote.

The researchers also found that although black women had the highest overall rate of postpartum death, non-Hispanic white women and women whose delivery costs were covered by Medicaid or paid by the patient had an elevated risk of drug-related death or suicide.

In discussing the limitations of their study, the study authors stated that data from California may not apply to the entire nation and called for further research.

“An important first step would be further documentation of this problem across the U.S., which will require that all state Maternal Mortality Review Committees (MMRCs) categorize deaths due to drugs, suicide, and other non-obstetric causes as medical deaths that fall within the scope of their review, particularly in [the] wake of congressional legislation providing funding for all states to form MMRCs,” they wrote.

For related information, see the Psychiatric News article “Is Postpartum Depression a Unique Psychiatric Disorder?” and the Psychiatric Services article “Use of Text Messaging for Postpartum Depression Screening and Information Provision.”

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APA Member Patrice Harris, M.D., Inaugurated AMA’s 174th President

“We are no longer at a place where those with mental illness and addiction are hidden and ignored, but we are not yet at a place where mental disorders are viewed without stigma and truly integrated into health care,” said long-time APA member Patrice A. Harris, M.D., M.A., in her address last night after her inauguration as the AMA’s 174th president.

Harris, a former member of the APA Board of Trustees, was sworn in during a ceremony at the AMA’s House of Delegates meeting in Chicago. Administering the oath of office was Jack Resnick, M.D., chair of the AMA Board of Trustees.

Harris, who is the first African American woman president of the AMA, said during her address that diversity and inclusion are critical to closing the gap in health disparities and that a focus of her presidency will be on health equity and increasing the diversity of the physician workforce.

“We face big challenges in health care today, and the decisions we make now will move us forward in a future we help create,” she said. “We are no longer at a place where we can tolerate the disparities that plague communities of color, women, and the LGBTQ community. But we are not yet at a place where health equity is achieved in those communities.”

Harris also vowed to elevate mental health as a part of overall health and to increase the understanding of the impact of childhood trauma on health.

During her presidential year, Harris will continue to chair the AMA’s Task Force to Reduce Opioid Abuse, which she has chaired since its inception in 2014.

Harris served as director of health services in Fulton County, Ga., and head of the Fulton County Department of Behavioral Health and Developmental Disabilities. As chief health officer for Fulton County, she spearheaded efforts to integrate public health, behavioral health, and primary care.

First elected to the AMA Board of Trustees in 2011, she has held the executive offices of AMA board secretary and AMA board chair. In addition to her leadership of the opioid task force, Harris has been active on AMA task forces and committees dealing with such issues as health information technology, payment and delivery reform, and private contracting. She also chaired the influential AMA Council on Legislation and co-chaired the Women Physicians Congress.

She served as trustee-at-large on the APA Board of Trustees from 2001 to 2004. In addition, she was president of the Georgia Psychiatric Physicians Association and founding president of the Georgia Psychiatry Political Action Committee.

APA leaders hailed her election as an important indication of the strength of psychiatry within the House of Delegates. “We look forward to the opportunity to continuing to work with Dr. Harris on many issues, including further collaboration within the house of medicine to improve the quality of care for our patients,” said APA President Bruce Schwartz, M.D.

APA CEO and Medical Director Saul Levin, M.D., M.P.A., said, “We are honored and delighted to have a psychiatrist and long-time APA member leading the house of medicine as president of the AMA. Her work over the years at APA and the AMA will add value to her new role as the face of the AMA.”

For related information, see the Psychiatric News article “APA Member Patrice Harris Chosen AMA’s President-Elect.”

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Children Whose Parents Have SMI Face Greater Risk of Self-Harm, Somatic Illness, Death

Children who have a parent with a serious mental illness (SMI) are at a greater risk of physical illnesses and death, according to a report in Schizophrenia Bulletin, highlighting the need for greater support of these children by the mental health community.

“Genetic vulnerability and lifestyle could be playing a role in the children’s increased risk,” wrote Anne Ranning, Ph.D., of Copenhagen University Hospital and colleagues. “Children may adapt to parents’ behavioral disposition with regard, for instance, to physical activity, smoking habits, and dietary patterns. Moreover, it has been suggested that SMI might in some cases be linked to a dysfunction in the immune system, which may also affect the child’s risk of general medical illnesses.”

The researchers conducted a register-based nationwide study of more than 2 million children born in Denmark between 1982 and 2012. These children were followed until their first hospital visit for a somatic illness or until their death. The maximum age of the offspring at follow-up was 30 years. Outcomes for children with a parent with SMI (parent had been diagnosed with depression, bipolar disorder, or schizophrenia) were then compared with outcomes for children whose parents did not have SMI.

Having at least one parent with SMI was associated with a 17% increase in likelihood of hospital contact for physical illness and a 31% increase in mortality rate compared with children whose parents did not have SMI, Ranning and colleagues reported. Compared with children who did not have a parent with SMI, those whose mothers had depression had a 22% greater risk of a hospital visit for physical illness, while those whose mothers had bipolar disorder had more than double the risk of death. Furthermore, the authors found that children whose parents had SMI and comorbid substance abuse were at higher risk for somatic illness and death.

Children with parents with SMI were more likely to have a variety of conditions, including endocrine/metabolic diseases, infections, and injury, the researchers found. The greatest risk of injury among children with a parent with SMI was intentional self-harm.

“Due to their increased risk of mental disorders, the children of parents with mental illness constitute an at-risk population; hence, selective preventive interventions are widely recommended to shift expected trajectories toward mental illness and social adversity,” Ranning and colleagues wrote. They recommended interventions to reduce risk factors and promote resilience such as family therapy, parenting and problem-solving skills training, and emotional well-being skills training for children and parents.

For related information, see the Psychiatric Services article “Randomized Controlled Trial of an Internet-Based Educational Intervention for Mothers With Mental Illnesses: An 18-Month Follow-Up.”

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Esketamine Plus Antidepressant Maintenance Delays Relapse in Refractory Depression, Study Finds

In patients with treatment-resistant depression who responded to intranasal esketamine plus an antidepressant, maintaining that treatment regimen significantly reduced their risk of relapse, according to a study in JAMA Psychiatry. 

Previous studies have confirmed the short-term antidepressant efficacy of esketamine, which was recently approved by the Food and Drug Administration for treatment-resistant depression. (AJP in Advance in May published a study showing patients with treatment-resistant depression who took esketamine nasal spray plus a new oral antidepressant for 28 days experienced significant symptom improvements over those treated with placebo nasal spray plus a new oral antidepressant.) Still, little is known about the long-term effects of esketamine, according to Ella Daly, M.D., of Janssen Research and Development and colleagues. 

This recent study is part of SUSTAIN-1, a multi-phased, randomized, controlled trial designed to compare 56 mg or 84 mg of esketamine nasal spray plus an antidepressant versus placebo nasal spray plus an antidepressant in patients with treatment-resistant depression. 

Daly and colleagues enrolled 297 adults with depression who had achieved a stable response (n=121) or stable remission (n=176) with esketamine plus an oral antidepressant during the 16-week first phase of SUSTAIN-1. Stable response was defined as a minimum 50% reduction from baseline in the Montgomery-Åsberg Depression Rating Scale (MADRS) in the last two weeks of initial treatment. Stable remission was defined as a MADRS score of 12 or lower for at least three of the last four weeks of initial treatment. 

For the maintenance phase of the study, the participants were randomized to continue esketamine-antidepressant treatment or switched to an antidepressant plus placebo nasal spray. The participants remained in this phase until they had a depression relapse or withdrew from the study. Relapse was defined as a MADRS score of 22 or higher for two consecutive assessments or hospitalization for worsening depression, suicide attempt, suicide prevention or completed suicide, or another clinical event indicating relapse.

“Continued treatment with esketamine and antidepressant significantly delayed relapse compared with treatment with antidepressant and placebo,” Daly and colleagues wrote. Among patients who responded, 25.8% who continued esketamine and 57.6% who received placebo nasal spray experienced depression relapse. Among those who remitted, 26.7% in the esketamine group and 45.3% in the placebo group had a relapse. The authors calculated that esketamine reduced relapse risk by 51% among stable-response patients and by 70% among stable-remission patients. 

The researchers reported no new or unexpected safety findings. 

For related information, see the AJP in Advance article “Efficacy and Safety of Flexibly Dosed Esketamine Nasal Spray Combined With a Newly Initiated Oral Antidepressant in Treatment-Resistant Depression: A Randomized Double-Blind Active-Controlled Study.”

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APA Endorses New Parity Enforcement Legislation, Urges Speedy Passage

APA has endorsed the Mental Health Parity Compliance Act, a bipartisan bill introduced in the Senate today that would enhance the transparency and accountability of insurers’ coverage of mental and substance use disorders, in compliance with the federal parity law.

That law, the Mental Health Parity and Addiction Equity Act of 2008, requires health plans to cover mental and substance use disorders the same as other medical illnesses; however, there is a lack of oversight to ensure that patients are receiving equal coverage of psychiatric conditions under the law. Plans that are subject to the Employee Retirement Income Security Act of 1974 (ERISA), or self-funded employment plans, are outside the enforcement jurisdiction of state agencies. The new legislation, co-sponsored by Sen. Chris Murphy (D-Conn.) and Sen. Bill Cassidy (R-La.), will tighten parity enforcement of these ERISA plans.

“For too long insurers have neglected their responsibility to adequately provide coverage for patients with mental illness or substance use disorders,” said APA President Bruce Schwartz, M.D. “This bill will help to ensure those patients be treated like patients with any other illness and end this harmful discrimination.”

Insurers have used a variety of means to sidestep the parity law and reduce utilization of mental health services, including inadequate reimbursement rates for psychiatrists and mental health professionals and “skinny” networks; the latter refer to health insurance provider networks that have few mental health professionals available to treat patients. In some cases, health plans have been found to have “phantom networks” that may include physicians who are no longer accepting patients, have moved out of a geographic area, or are deceased.

“We wholeheartedly support this bill, and we urge the Senate and the House to take this up soon and pass it,” said APA CEO and Medical Director Saul Levin, M.D., M.P.A. “Our patients depend on insurance for their care.”

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Methylphenidate Remains Effective for ADHD After Two Years of Regular Use

There is a wealth of evidence that methylphenidate can improve attention-deficit/hyperactivity disorder (ADHD) symptoms in the short term, but there are limited data on the long-term benefits of this medication. According to a study in AJP in Advance, youth with ADHD who have taken methylphenidate for two or more years continue to benefit from methylphenidate when compared with peers who are temporarily taken off this medication.

Anne-Flore Matthijssen, M.Sc., of Groningen University in the Netherlands and colleagues enrolled 94 children and adolescents aged 8 to 18 who had been taking methylphenidate regularly for at least two years. The participants were randomly assigned to either continue their treatment or go on gradual discontinuation (three weeks of drug tapering followed by four weeks of placebo medication).

At the end of seven weeks, ADHD symptom scores (assessed with the investigator-rated ADHD Rating Scale) remained stable among children taking methylphenidate (from 21.4 to 21.9) but increased among those who discontinued the medication (from 19.6 to 24.7). Similar outcomes were seen when using a teacher-rated symptom assessment (Conners’ Teacher Rating Scale–Revised: Short Form).

The authors found that the benefits of continuing to take methylphenidate were superior among participants 13.8 years and younger; youth older than 13.8 years did not have significantly worse symptoms on average upon discontinuing their medication.

Matthijssen and colleagues cautioned that most eligible families they contacted declined to enroll their children. “[O]ur sample likely included an overrepresentation of families who suspected that the medication may not have been working well and therefore wanted to try going off medication,” the authors wrote. “Those who declined to participate may have felt more confident that the medication was helpful and may therefore have been unwilling to risk being assigned to the placebo condition.” This recruitment issue may partially explain why the differences between the methylphenidate and discontinuation groups was modest.

“Nevertheless, the fact that most participants in our study did not experience significant worsening after discontinuation of methylphenidate supports guideline recommendations to periodically assess whether there is a continued need for methylphenidate treatment, for example, by considering a temporary discontinuation of medication in clinical practice to prevent unnecessary long-term medication use,” the authors concluded.

For related information, see the Psychiatric News article “Noninvasive Electrical Stimulation Shown Effective for ADHD.”

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