Friday, May 20, 2022

Dextromethorphan-Bupropion Significantly Improves Depression Symptoms, Study Finds

Patients with major depressive disorder (MDD) who take a combination of dextromethorphan and bupropion may experience greater symptom improvements than those taking bupropion alone, suggests a small study published Wednesday in the American Journal of Psychiatry. The study was funded by Axsome Therapeutics, which is developing an oral formulation of dextromethorphan and bupropion.

“This study is the first controlled trial of dextromethorphan-bupropion in patients with depression,” wrote Herriot Tabuteau, M.D., of Axsome Therapeutics Inc. and colleagues. “[T]reatment with dextromethorphan-bupropion resulted in clinically meaningful and statistically significant improvements in depressive symptoms compared with the active comparator bupropion, and was well tolerated.”

Tabuteau and colleagues analyzed data from a six-week, randomized, double-blind phase 2 trial including 80 participants aged 18 to 65 years. All participants had a confirmed MDD diagnosis and were experiencing a major depressive episode of moderate or greater severity. They were randomly assigned to receive either dextromethorphan-bupropion (45 mg/105 mg tablet) or bupropion (105 mg tablet) once daily for the first three days of the trial, and twice daily for the remainder of the six-week trial.

Depression severity was defined as participants’ ratings on the Montgomery-Åsberg Depression Rating Scale (MADRS), with higher scores representing more severe depression. MADRS was completed at baseline and at weeks one, two, three, four, and six. Clinical response was defined as a reduction of at least 50% from baseline in MADRS score, while remission was defined as a MADRS score of 10 or less.

Participants treated with dextromethorphan-bupropion were significantly more likely to experience a reduction in their MADRS scores between baseline and six weeks compared with those who received bupropion. By the end of the trial, participants in the dextromethorphan-bupropion group had an average reduction of 17.3 points on the MADRS scale, compared with 12.1 points for those in the bupropion group. Further, 46.5% of participants in the dextromethorphan-bupropion group entered remission by the end of the study, compared with 16.2% in the bupropion group. Finally, 60.5% of those in the dextromethorphan-bupropion group achieved a clinical response by the end of the study, compared with 40.5% in the bupropion group.

In the dextromethorphan-bupropion group, 72.9% of participants reported adverse events, such as dizziness, nausea, and anxiety, compared with 64.6% in the bupropion group. The majority of adverse events were mild or moderate, and no serious adverse events, such as hospitalizations, occurred.

“Dextromethorphan-bupropion rapidly reduced depressive symptoms, as measured by the MADRS total score, as early as week 1, with statistically significant differences over bupropion observed by week 2 and at every time point thereafter,” the authors wrote.

For related information, see the Psychiatric News article “Bupropion May Be Best for Overweight Patients With Depression.”

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APA Annual Meeting Kicks Off Tomorrow

After a two-year hiatus, it’s time to reconnect with your friends and colleagues in person at APA’s 2022 Annual Meeting, which gets underway this Saturday, May 21, in New Orleans. To make the most of your meeting experience, download the APA Meetings App, which can be searched by the scientific program by day, format, topic, or speaker. You can also use the app to browse some of the 190 exhibitors who will be showcasing technology and services at the Exhibit Hall.

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Thursday, May 19, 2022

Poor Sleep Habits Linked to Binge Drinking Among Adolescents

Adolescents who prefer going to sleep later in the evening, are sleepy during the day, and sleep for shorter periods of time are more likely to participate in severe binge drinking the following year, according to a study published Tuesday in Alcoholism.

“Growing longitudinal evidence indicates that late childhood and adolescent sleep characteristics predict alcohol and cannabis use and related problems in later adolescence and young adulthood,” wrote Brant Hasler, Ph.D., of the University of Pittsburgh and colleagues. “These findings extend a growing literature supporting the relevance of sleep/circadian characteristics to risk for alcohol and cannabis use.”

Hasler and colleagues used data from six annual assessments from 801 participants enrolled in the National Consortium on Alcohol and Neurodevelopment in Adolescence (NCANDA) study. Participants, aged 12 to 21 years at baseline, were interviewed to determine past-year alcohol use, cannabis use, and severity of binge drinking. The authors defined binge drinking based on a scale determined by age, ranging from three or more drinks for participants 13 and younger, up to five or more drink for male participants 18 and older, and four or more drinks for female participants 18 and older. Participants were considered to have engaged in heavy binge drinking if they reported consuming double the initial age-based binge levels and extreme binge drinking if they consumed triple the initial levels.

As part of the NCANDA study, the participants were also asked about their sleep habits, including circadian preference (meaning what time participants prefer to wake up and go to bed), past-month sleep quality, daytime sleepiness, and what time participants typically went to bed and woke on both weekdays and weekends.

Adolescents who reported a preference for going to bed later and waking later, greater daytime sleepiness, and shorter sleep duration on both weekdays and weekends were more likely to binge drink the next year, the researchers found. Further, shorter sleep duration on weekends was the predominant predictor of future binge drinking severity when compared with all the sleep measures, with one hour less sleep on weekends resulting in 19% increased risk for severe binging the following year. Preferring a later bedtime and wake time was also associated with a higher risk of cannabis use the next year.

“Sleep is a modifiable behavior in adolescents … and, consequently, adolescent sleep may be a viable target for reducing substance use risk through, for example, policy-level changes delaying school start times,” the authors concluded.

For related information, see the Psychiatric News article “Short Sleep Duration Increases Adolescent Suicide Risk.”

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Just a Few Weeks Left to Submit Abstracts for Mental Health Services Conference

The 2022 Mental Health Services Conference will empower all mental health service providers with practical tools and innovations to shape the future of community collaboration. Held in person in Washington, D.C., at the Capital Hilton Hotel on October 13-14, the conference will provide up to 18 continuing education credits for physicians, psychologists, social workers, and nurses. The deadline for abstracts is Thursday, June 2, at 5 p.m. ET.

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Wednesday, May 18, 2022

COVID-19–Related Trauma Reported by 40% of People With Mental Illness

About 40% of people with a history of psychiatric disorder reported having found some aspect of the COVID‐19 pandemic to be traumatic, according to a report in Depression and Anxiety. However, only about 5% of these people reported a traumatic event that met criteria for diagnosing posttraumatic stress disorder (PTSD), such as exposure to actual or threatened death or a threatening series of events.

Younger people, those with low income and lower social support, financial worries, and/or lived experience of PTSD were most likely to report traumatic stress symptoms.

“It is important to note that in the context of such a widespread event, even a very small percentage of people with PTSD amounts to a significant mental health burden,” wrote Catrin Lewis, Ph.D., of the National Centre for Mental Health at Cardiff University School of Medicine in the United Kingdom and colleagues.

The researchers surveyed 1,571 individuals with lived experience of psychiatric disorder who were participants in a longitudinal study of mental health during the COVID‐19 pandemic by the Welsh National Centre for Mental Health. Participants included those with lived experience with bipolar disorder, schizophrenia, depression, anxiety, eating disorders, personality disorder, PTSD, and autism spectrum disorders.

The participants were asked if they found any aspect of the COVID‐19 pandemic traumatic (yes/no); if they answered “yes,” they were prompted to share their most troubling experience. The researchers then judged whether that description met the traumatic stressor criterion of ICD‐11 (defined as “exposure to an extremely threatening or horrific event or series of events”) and/or DSM‐5 (defined as “exposure to actual or threatened death, serious injury, or sexual violence”). Additionally, participants who reported a traumatic experience completed the PTSD subscale of the International Trauma Questionnaire.

A total of 630 participants (40.10%) found some aspect of the pandemic traumatic, with generalized worry about the pandemic (12.22%) and lockdown/social distancing restrictions (8.47%) being the “most troubling” experiences reported most frequently. However, 5.28% reported a traumatic exposure that met the traumatic stressor criterion according to ICD‐11 and 3.06% according to DSM‐5. Traumas that met criteria according to both ICD‐11 and DSM‐5 included experiencing severe symptoms of COVID‐19 and witnessing another person being critically unwell or dying.

“Given the often‐chronic nature of PTSD, identifying risk factors for its development is vital, whilst being cautious not to unnecessarily pathologize transient reactions,” the researchers wrote. “Clinical services would benefit from being trauma‐informed and equipped to deal with PTSD on its own or in combination with other conditions.”

For related information, see the Psychiatric News article “40% of Adults Reported Worsening Mental Health During Pandemic.”

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Tuesday, May 17, 2022

Policies That Criminalize Perinatal Substance Use Linked to Poor Outcomes in Mothers

State policies that criminalize or punish pregnant women and adolescent girls for prenatal substance abuse may have a negative impact on outcomes such as opioid overdose and seeking treatment for opioid use disorder (OUD), a study in the Journal of Substance Abuse Treatment has found. The study also found that state policies that support treatment and early intervention may result in better outcomes for pregnant women and adolescent girls.

Angélica Meinhofer, Ph.D., of Weill Cornell Medicine and colleagues analyzed data from 164,538 females between the ages of 15 and 45 years who had a diagnosis of OUD between 2006 and 2019, of which 13% were pregnant at least once during that time. The researchers compared changes in outcomes in pregnant women and adolescent girls in states with and without a prenatal substance use policies, before and after the implementation of the policies. They defined punitive policies as those that criminalize prenatal substance use (that is, defining prenatal substance exposure as child maltreatment in child welfare statutes or as grounds for termination of parental rights) or use other punitive approaches. They defined supportive prenatal substance use policies as those policies that create or fund targeted substance use disorder (SUD) treatment programs specifically for pregnant females or make SUD treatment for pregnant females a priority.

The researchers found that after states implemented punitive policies, the proportion of pregnant females receiving psychosocial services for SUD and methadone services decreased. Furthermore, opioid overdoses increased 45% in states that implemented policies that criminalize pregnant females for using substances. In contrast, following the implementation of supportive policies that fund targeted SUD programs for pregnant females, the proportion of opioid overdoses decreased 45% and the proportion of pregnant females taking any medication for the treatment of OUD increased 11%. However, the researchers found that policies that made SUD treatment for pregnant females a priority were not associated with statistically significant changes in outcomes such as use of medications for OUD.

“[O]ur findings highlight the nation’s trend toward more punitive [policies] as a cause of concern, as our findings suggest that some punitive policies may negatively impact perinatal health outcomes,” the researchers wrote. “Our findings support the recommendations made by leading medical organizations who oppose punitive policies and emphasize efforts that focus on rehabilitation and treatment to minimize adverse health outcomes associated with substance use disorder.”

For related information, see the Psychiatric News article “Statutes Prosecuting Pregnant Women with OUD May Backfire.”

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Monday, May 16, 2022

Study Compares Efficacy of Ketamine vs. Esketamine in Clinical Setting

Intravenous ketamine may improve patients’ depressive symptoms more rapidly than intranasal esketamine, according to a report in JAMA Psychiatry.

Sina Nikayin, M.D., of Yale University and colleagues reviewed medical data from adults with major depressive disorder who received ketamine or esketamine therapy at the Interventional Psychiatry Service at Yale New Haven Psychiatric Hospital between September 2016 and April 2021. The sample included 129 individuals who received ketamine (0.5 mg/kg over 40 minutes per session) and 81 who received esketamine (56 mg or 84 mg spray per session). The demographic characteristics of the two groups were similar: Patients were predominantly non-Hispanic White with private insurance.

After six treatments administered at least weekly, patients who received ketamine had lower average scores on both the clinician-administered Montgomery Åsberg Depression Rating Scale (MADRS) and Quick Inventory of Depressive Symptomatology–Self-Report (QIDS-SR) compared with patients in the esketamine group. After a full course of treatment (up to eight treatments), QIDS-SR scores remained lower in the ketamine group; there was no statistical difference in MADRS scores between the two groups after eight treatments.

Patients in both groups also had statistically similar rates of treatment response (defined as 50% or greater improvement in MADRS scores), depression remission (MADRS scores of 10 or less), and suicidal ideation (score on MADRS question 10 or QIDS-SR question 12). Overall remission rates were 29.6% for patients taking ketamine and 24.0% for patients taking esketamine. Nikayin and colleagues noted these rates are lower than those reported in other studies, likely because the Yale Interventional Psychiatry Service is a tertiary referral center that treats the most severely ill patients.

“Although both treatments reduce symptoms, these findings signal a potential difference [for ketamine] that could be attributable to many factors, including dosing, delivery mechanism, role of arketamine [chemical mirror image of esketamine], or patient expectations,” the researchers wrote. “A randomized trial is needed to determine the comparative efficacy of these treatments.”

To read more on this topic, see the American Journal of Psychiatry article “Synthesizing the Evidence for Ketamine and Esketamine in Treatment-Resistant Depression: An International Expert Opinion on the Available Evidence and Implementation.”

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Friday, May 13, 2022

Driving Under the Influence Common Among People Who Use Methamphetamine, Cocaine

Nearly half of adults who have used methamphetamine during the last year have driven while under the influence, a study in Addictive Behaviors has found. The study also revealed that more than one-fifth of adults who have used cocaine in the last year have driven under the influence.

Trenette C. Goings, Ph.D., of the University of North Carolina at Chapel Hill and colleagues examined data from 170,944 adults aged 18 years and older who participated in the annual National Survey on Drug Use and Health between 2016 and 2019. As part of this survey, participants were asked if they had used cocaine or methamphetamine in the previous 12 months or driven under the influence of either of these substances in the previous 12 months.

Among those who reported using these substances in the previous 12 months, 47.2% who used methamphetamine and 21.6% who used cocaine reported driving under the influence in the same time frame, respectively.

“This is noteworthy given evidence suggesting cocaine-influenced driving … is considered to be more dangerous than [driving under the influence] of cannabis and comparable to driving with relatively low blood alcohol concentration,” the researchers wrote. “Moreover, methamphetamine-influenced driving … is understood as comparable to or more dangerous than driving beyond legal [blood alcohol content] limits.”

Among adults who reported past-year use of cocaine or methamphetamine, those who drove while under the influence were more than twice as likely to have also experienced a depressive episode or psychological distress in the past year compared with those who used the substances but did not drive under the influence.

“[T]his greater likelihood of depressive symptoms might relate to psychological distress as a potential driver of increased substance use, which in turn, places individuals at greater risk of [driving under the influence of stimulants],” Goings and colleagues wrote. “Alternatively, or as a complement, we know depression is not only a primary symptom of cocaine/methamphetamine withdrawal, but also increased risk for depression is a long-term consequence of stimulant use.”

For related information, see the chapter “Substance-Related and Addictive Disorders” in The American Psychiatric Association Publishing Textbook of Psychiatry, Seventh Edition.

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Thursday, May 12, 2022

Youth Who Transition to Another Gender Not Likely to Transition Back, Study Finds

Youth who socially transition to a gender other than the sex they were assigned at birth are likely to continue identifying as that gender five years later, according to a study published in Pediatrics.

“These results suggest that retransitions are infrequent. More commonly, transgender youth who socially transitioned at early ages continued to identify that way,” wrote Kristina Olson, Ph.D., of Princeton University and colleagues. “Nonetheless, understanding retransitions is crucial for clinicians and families to help make them as smooth as possible for youth.”

Olson and colleagues used data from the Trans Youth Project, a longitudinal study involving 317 youth aged 3 to 12 years old. All participants were recruited between July 2013 and December 2017. Prior to joining the study, the youth had to have socially transitioned to a gender other than their sex assigned at birth—a process that typically involves changing their pronouns, first names, hairstyles, and clothing.

The authors used reports from youth and their parents to determine whether the youth retransitioned (meaning they transitioned again after their initial transitions) or if they continued to identify as their transitioned gender several years later. Participants were classified into three categories based on the pronouns they used: binary transgender (the child identified as the transitioned gender), nonbinary (the child used they/them pronouns), or cisgender (the child again identified as the sex they were assigned at birth).

An average of 5.37 years after their initial transitions, 94% of participants were living as binary transgender, 2.5% identified as cisgender, and 3.5% identified as nonbinary. The rate of retransitions among the participants was 7.3%, and four participants (1.3%) had retransitioned twice, to a nonbinary then back to transgender. Most retransitions occurred before the youth reached age 10. Youth who initially socially transitioned before age 6 were more likely to be living as cisgender five years later compared with youth who transitioned at age 6 or later.

Concerns that youth will experience regret after transitioning, particularly after starting hormone therapy, has led some physicians and even legislatures to question the ability of minors to consent to gender-affirming treatment, wrote Christina Roberts, M.D., M.P.H., of Children’s Mercy in Kansas City in an accompanying editorial. The “stability of transgender identity” five years after the initial transition, as evidenced in Olson’s study, should reassure physicians when recommending gender-affirming treatment, Roberts wrote.

She continued: “The low risk of regret should also inform the actions of legislators attempting to substitute their judgment for the judgment of patients, parents, and providers by denying transgender adolescents access to this evidence-based and potentially life-saving treatment.”

For related information, see the Psychiatric News articles “Record Number of Anti-Trans Bills Filed in States This Year” and “Psychiatrists Need to Prepare to Care for Gender-Variant Patients.”

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