Among Teen Girls With Anorexia, Actual Weight Not Associated With Self-Esteem

In adolescent girls with anorexia nervosa (AN), body dissatisfaction and self-esteem are related to negatively biased perceptions about their bodies, not their actual weight, according to a study published this week in the Journal of Eating Disorders.

“Low self-esteem and high body dissatisfaction are pivotal risk factors for eating disorders that are closely linked and mutually reinforce each other in both non-clinical samples and individuals with eating disorders,” wrote Linda Lukas, M.Sc., of University Hospital Ludwig-Maximilians-University in Munich, Germany, and colleagues. “These risk factors might play a particularly important role in adolescents, who are in a critical stage of identity formation and subject to rapidly changing perceptions, thoughts, and feelings about their developing bodies. This leaves them especially vulnerable to constant comparison to the unrealistic images portrayed in the media.”

Lukas and colleagues recruited 40 adolescent girls with AN and 40 without any mental disorders ages 12 to 18 (median age 15). The researchers calculated participants’ BMI, assessed their body dissatisfaction using the Body Shape Questionnaire, and assessed their self-esteem using the Rosenberg Self-Esteem Scale. Participants’ interpretation bias was determined using the Scrambled Sentences Task, in which they were presented with scrambled sentences relating to their bodies (such as “my fat bottom find attractive I”); participants then had to rearrange the sentences using five of the presented words, with each sentence allowing them to choose a positive (“I find my bottom attractive”) or negative (“I find my bottom fat”) solution. The researchers then calculated participants’ interpretation bias based on how often they created negative sentences relative to positive ones.

Among participants with AN, BMI did not predict self-esteem or body dissatisfaction, while body-related interpretation bias was a significant predictor of both. A more negative interpretation of participants’ bodies was associated with higher body dissatisfaction and lower self-esteem, regardless of BMI. In contrast, among those without AN, both BMI and interpretation bias were significant predictors of self-esteem and body dissatisfaction, suggesting that both actual weight and perceptions of their bodies are linked to body dissatisfaction and self-esteem.

“These cognitive biases may distort how adolescents with AN perceive their bodies, preventing them from experiencing their bodies as thin, even when they are underweight, and may reinforce their belief that their bodies are flawed, unattractive, and not thin enough, thereby perpetuating their high body dissatisfaction and low self-esteem,” the authors wrote. “Addressing the dysfunctional cognitions related to one’s body may facilitate interrupting dysfunctional associations between low self-esteem, body dissatisfaction, and disordered eating behaviors.”

For related information, see the Psychiatric News Special Report “Youth With Eating Disorders—Time Is of the Essence in Achieving Remission.”

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Hepatitis C May Help Cause Behavioral Symptoms of Schizophrenia, Bipolar Disease

Hepatitis C virus (HCV) may cross into the lining of the brain and thus help cause behavioral symptoms in schizophrenia and bipolar disorder, according to a study in Translational Psychiatry.

Maree J. Webster, Ph.D., of the Stanley Medical Research Institute, and colleagues performed RNA sequencing on postmortem brain samples from 84 people with schizophrenia, 73 with bipolar disorder, 23 with major depressive disorder (MDD), and 76 controls. The researchers took the samples from each brain’s choroid plexus, a collection of cells that make up the lining of the brain’s fluid-filled cavities and produce the fluid that protects the brain and spinal cord. (Viruses are known to target the choroid plexus.)

The researchers found more viruses overall, including herpesviruses, in samples from people with schizophrenia or bipolar disorder than in controls or samples from people with MDD. But, unlike other viruses, HCV was only present in choroid plexus samples of people who had schizophrenia or bipolar disorder.

The researchers also analyzed the electronic health records of 285 million individuals, finding that the prevalence of chronic HCV was 3.6% and 3.9% in people with schizophrenia and bipolar disorder, respectively, whereas it was 1.8% in people with MDD and .5% in people without psychiatric disorders.

“Our findings provide compelling support for the viral hypothesis of psychiatric disease and identify HCV as a feasible viral pathogen that contributes to the neuropathology of [schizophrenia] and [bipolar disorder],” the researchers wrote. “Given that the worldwide rate of [schizophrenia] and [bipolar disorder] is approximately 1% and 3%, respectively, identifying and immediately treating the small subset of patients infected with HCV has the potential to improve psychiatric symptoms for hundreds of thousands of people.”

For related information, see the Psychiatric News article “A Call to Action: Test Our Patients for Hepatitis C.”

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Several Interventions Can Effectively Address Mental Health Symptoms Among Physicians

Face-to-face, skills-based interventions such as mindfulness and mind-body programs show promise in preventing or reducing common mental health disorder symptoms among physicians, according to a meta-analysis published in Nature Mental Health.

“Physicians have elevated rates of common mental disorder, specifically depression and anxiety, and are at increased risk of death by suicide compared with all other professional groups and the general population,” wrote Katherine Petrie, Ph.D., of the University of New South Wales in Australia, and colleagues. “[T]hese results provide important guidance for workplaces as to some promising interventions that could improve the mental health of this workforce.”

The researchers identified 21 studies that included 2,336 experienced physicians and residents (mean age of 35 years) and analyzed the impact of a variety of interventions to address anxiety, depression, or general psychological distress. The interventions included mindfulness- and mind-body-based approaches, psychoeducational approaches, and cognitive behavioral therapy (CBT), among others. Some were held face-to-face while others were delivered digitally, and they included both group-based and individual interventions.

The authors found that a range of interventions resulted in a moderate reduction in depression, anxiety, or general psychological distress symptoms among physicians. Mindfulness- and mind-body-based interventions were particularly effective in reducing symptoms, as were skills-based approaches such as CBT, stress management, and peer support. By contrast, interventions that used a psychoeducational approach did not significantly reduce symptoms compared with control conditions. Additionally, the authors found that interventions delivered face-to-face were more effective than those delivered digitally.

“[T]hese findings highlight the need for careful consideration and planning around how these programs can be implemented into the ongoing professional education and working environment of physicians,” the authors wrote. “There is a balance to be struck between efficacy and issues of scalability, feasibility and sustainability…. [T]he direct and indirect costs of physician ill health to the health-care system (for example, presenteeism, absenteeism, turnover) should be a key consideration in this decision-making process, and the use of protected time or continuing professional development points may be a means to encourage adherence and ensure program completion.”

For related information, see the Psychiatric News article “Investing in Residents’ Mental Health Vital to Psychiatry’s Own Health.”

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Metformin May Curb Weight Gain in Youth Who Take Antipsychotics

Taking metformin may help overweight or obese adolescents who take antipsychotic medications avoid the weight gain commonly associated with the drugs, according to researchers in the multicenter Metformin for Overweight and Obese Children and Adolescents With Bipolar Spectrum Disorders Treated With Second-Generation Antipsychotics (MOBILITY) study. The results were recently published by the Patient-Centered Outcomes Research Institute.

Melissa P. DelBello, M.D., M.S., of the University of Cincinnati, and colleagues examined data from 1,565 youth ages 8 to 19 years who had a diagnosis of bipolar disorder and had overweight or obesity. All patients had an established history of taking a second-generation antipsychotic medication or had recently begun taking one shortly before enrollment.

The patients and their caregivers viewed a seven-minute educational video and received printed materials about healthy diet and exercise. The researchers then randomized the patients to either lifestyle alone or lifestyle plus metformin. For the metformin group, the researchers recommended starting at a dose of 500 mg daily and increasing to a maximum dose of 1,000 mg twice daily, but dosing was flexible and carried out according to clinical discretion. The researchers collected data about the patients’ height, weight, and BMI at baseline and at a maximum of 10 follow-up visits, which were recommended monthly for the first three months and every three months after that for up to two years. They also assessed the patients’ weight-related quality of life using the Sizing Me Up & Sizing Them Up scale, a 22-item self-report and parent-proxy measure of obesity-specific health-related quality of life for youth that includes subscales for emotional, physical, and school functioning as well as teasing/marginalization, positive social attributes, mealtime challenges, and social distress/avoidance.

At six months and two years, the patients in the metformin/lifestyle group had greater reductions in BMI than those in the lifestyle-only group along with greater improvements in quality of life. However, they also had more adverse events, including 12 serious adverse events necessitating or prolonging hospitalization such as abdominal pain and refractory headache. Eleven percent of patients in the metformin/lifestyle group discontinued metformin because of gastrointestinal side effects.

“Based on our assessment … of the risks and benefits of adding [metformin] to a brief healthy lifestyle intervention among youth with [bipolar disorder] who have overweight or obesity, clinicians should strongly consider prescribing [metformin] in conjunction with [second-generation antipsychotics],” the researchers wrote. “… Although most clinicians regularly assess mood symptoms in this population, the striking prevalence of [quality-of-life] impairments directly related to weight underscores the importance of discussing with patients and their caregivers how weight gain may be adversely affecting their lives.”

For related information, see the Psychiatric News articles “Metformin May Reduce Weight Gain in Youth Taking Antipsychotics” and “New Guideline Calls for Metformin to Prevent Antipsychotic-Induced Weight Gain.”

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Few Mental Health Facilities Offer Medications for AUD—Not Even Those That Provide Other SUD Services

Just 10% of mental health treatment facilities offer medications for alcohol use disorder (AUD), according to a research letter published today in JAMA Network Open.

Perhaps more concerning, only about 40% of facilities that provide both mental health and substance use disorder (SUD) services offer medications for AUD—a disorder estimated to affect more than 11 million adults in the United States.

Susan H. Busch, Ph.D., of the Yale School of Public Health, and colleagues compiled data on 6,572 mental health and SUD facilities that provided outpatient care and responded to the 2023 National Substance Use and Mental Health Services Survey (hospitals, federal facilities, and residential treatment centers were excluded). Of these, 2,640 facilities primarily provided mental health services (but could potentially treat co-occurring SUD), while the remaining 3,932 facilities provided both primary mental health and primary SUD services.

Among the facilities specializing in mental health, just 262 (9.9%) reported offering medications for AUD, even though many such facilities offered other SUD services such as individual/group counseling or case management. Among the mental-health-plus-SUD facilities, 1,633 (41.5%) offered medications for AUD.

There were several differences in medication for AUD availability based on facility setting, region, and other characteristics. For example, among primary mental health facilities, medications for AUD were most likely offered at certified community behavioral health clinics (21.2%), whereas among mental-health-plus-SUD facilities, medications for AUD were most common at partial hospitalization/day treatment facilities (51.9%).

Busch and colleagues also found that medications for AUD were more likely to be offered at facilities that accepted insurance, those that had integrated primary care, and those that prescribed antipsychotics (the latter indicating the presence of a prescribing physician onsite).

“When people do not access substance use treatment due to misconceptions, ambivalence, stigma, or uncertainty about how to seek care, mental health facilities are uniquely positioned to help overcome these barriers,” Jennifer D. Ellis, Ph.D., wrote in an invited commentary. However, increasing uptake of evidence-based medications for AUD “requires buy-in of physicians, administrators, and clinic directors.”

Ellis cited multiple approaches to increase engagement with AUD medications, such as incentivizing screening and referral to treatment, increasing insurance coverage of these medications, and possibly leveraging accreditation organizations such as the Joint Commission to improve training and monitoring of staff.

For related information, see the Psychiatric News Alert “Stigma, Unfamiliarity Identified as Patient Barriers to Medications for AUD.”

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Anticholinergic Medications Results in Physical Performance Decline in Older Adults

Medications with strong anticholinergic burden, including some common psychiatric drugs, were tied to accelerated physical decline when used in older adults, suggesting these medications should be avoided in these patients, according to a study published today in JAMA Network Open.

Lower gait speed and grip strength are linked to poor health outcomes, such as new-onset disability and mortality, wrote Shelly L. Gray, Pharm.D., M.S., from the University of Washington in Seattle, and colleagues. “Drugs with anticholinergic and sedative properties are frequently prescribed to older adults, with prevalence ranging from 20% to 40%.... However, it is not known if long-term use has sustained associations with reduced physical function.”

Gray and colleagues looked at data from 4,283 adults 65 years or older without dementia at recruitment who attended at least two visits and had been enrolled for at least 10 years with Kaiser Permanente Washington. Researchers tallied participants’ exposure to medications deemed strong anticholinergics, including certain antipsychotics, sertraline and tricyclic antidepressants, benzodiazepines, and z-drugs. Researchers accounted for varying intensity, duration, and timing of past exposures to the medications to better estimate their cumulative effects and then correlated participants’ exposures to changes in their gait speed and grip strength.

Researchers found that higher cumulative anticholinergic exposure was associated with slightly larger decline rates in gait speed and grip strength beyond aging and comorbidities. Overall, their findings suggested that sustained high use of anticholinergics over several years could result in a gait speed decline that would reach the threshold of clinically meaningful.

Limitations of the study identified by the researchers included its predominantly White study population and the fact that prescribing guidance has recommended limiting anticholinergic use in older adults for several years. As a result, clinicians may have intentionally avoided these medications in older adults with multimorbidity and/or frailty—the group most likely to decline in physical performance—which could have minimized their findings.

“Anticholinergics are associated with numerous adverse outcomes in older adults; therefore, it is essential for clinicians to avoid their use when possible, prescribe the lowest effective dose, and periodically reevaluate patients to identify deprescribing opportunities to minimize potential harms,” researchers concluded.

For related information, see the Psychiatric News article “Anticholinergics Linked to Increased Risk of Dementia.”

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Salt May Increase Risk of Depression and Anxiety

Pass the salt, please … or maybe not? A study published this week in the Journal of Affective Disorders found that frequently adding salt to food is associated with an elevated risk of depression and anxiety.

Luyi Zhu, of the First Affiliated Hospital of Wenzhou Medical University, and colleagues collected data from 276,138 adults enrolled in the UK Biobank who reported not making any significant changes in their diet in the five years prior to enrolling. At baseline, the UK Biobank participants were asked: “Do you add salt to your foods? (Do not include salt used in cooking).” Responses included never/rarely, sometimes, usually, and always.

The researchers followed the individuals from baseline (2006 to 2010) until their first diagnosis of depression or anxiety, death, they left the study, or May 1, 2023—whichever occurred first. The median follow-up period was 14 years; over the follow-up, 10,486 individuals developed depression and 10,786 developed an anxiety disorder.

After adjusting for demographic (age, race, etc.), lifestyle (drinking, smoking, etc.), and clinical (weight, hypertension, etc.) variables, Zhu and colleagues calculated that compared with individuals who never/rarely added salt:

• Individuals who sometimes added salt had a 10% increased risk of depression and an 8% increased risk of anxiety.
• Those who usually added salt had a 19% increased risk of depression and an 8% increased risk of anxiety.
• Those who always added salt had a 45% increased risk of depression and a 24% increased risk of anxiety.

The researchers also found that an adequate intake of fruits and vegetables could mitigate the depression and anxiety risks of copious salt addition. “[I]ndividuals who have a sufficient intake of vegetables and fruits are likely to consume fewer processed foods, partially explaining the observed phenomenon,” they wrote. “Furthermore, numerous studies have affirmed the protective effects of the inherent nutritional components in vegetables and fruits against anxiety and depression.”

For related information, see the Psychiatric News Special Report “Using Nutrition as a Therapeutic Modality.”

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Antidepressant Discontinuation Symptoms Generally Nonserious

People who stopped taking antidepressants experienced one more withdrawal-like symptom on average than those who discontinued a placebo or stayed on the medications, according to a systematic review and meta-analysis issued today by JAMA Psychiatry today. Among the symptoms, however, mood worsening was not associated with discontinuation.

Michail Kalfas, M.Sc., of King’s College in London, and colleagues undertook the study due to the “lack of consensus and clarity on the evidence relating to incidence and duration of antidepressant discontinuation symptoms,” they wrote. “The proposed high incidence of discontinuation symptoms from [clinical trials] and surveys has had significant effects on policy and attitudes toward antidepressant use.”

The researchers identified 50 randomized clinical trials published before November 7, 2023, that assessed adults with various psychiatric disorders who stopped antidepressant treatment and whose discontinuation symptoms were assessed using standardized measures such as the Discontinuation Emergent Signs and Symptoms (DESS) scale. The 50 studies included 17,828 adults whose symptoms were followed for up to 52 weeks after abrupt or tapered discontinuation.

Kalfas and colleagues reported that discontinuation of antidepressants was associated with one additional symptom on the DESS after one week compared with those who continued an antidepressant or discontinued placebo. This falls significantly below the cutoff point of four or more symptoms considered to be a clinically significant discontinuation syndrome. Across antidepressants, dizziness was the most frequent symptom associated with antidepressant cessation, affecting 6% of participants after accounting for placebo effects. Other symptoms positively associated with antidepressant cessation included nausea, vertigo, headache, nervousness, and diarrhea.

Antidepressant discontinuation was not associated with greater depressive symptoms in the first two weeks compared with placebo, despite being measured in studies specifically examining major depressive disorder; this suggests that later presentation of depression symptoms is more likely to represent depression relapse, researchers wrote.

“The lack of evidence of prolonged withdrawal symptoms could reflect shorter duration of antidepressant use, although our findings do cast a degree of doubt on the need for routine use of longer-term tapering regimens…,” the researchers wrote. “Acknowledgment of the burden of discontinuation effects is crucial; nevertheless, it is important that professional practice and media narratives surrounding discontinuation effects are proportionate. Undue emphasis on discontinuation effects may increase the likelihood of real and debilitating symptoms, which arise (or are maintained) via processes distinct from pharmacological mechanisms.”

For related information, see the Psychiatric News article “About 1 in 6 Who Stop Antidepressants Experience Side Effects, but Rarely Severe.”

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Centanafadine May Improve ADHD Symptoms in Adolescents

The investigational drug centanafadine improved symptoms of attention-deficit/hyperactivity disorder (ADHD) in adolescents in a Phase 3 clinical trial. The results of the trial, which was sponsored by Otsuka Pharmaceutical Development & Commercialization, were published in the Journal of the American Academy of Child & Adolescent Psychiatry.

“Neurobiological and pharmacological ADHD research has focused on the roles of norepinephrine and dopamine. However, emerging evidence suggests that serotonin may also contribute to the disorder,” wrote Timothy E. Wilens, M.D., of Harvard Medical School, and colleagues. They noted that serotonin levels have been shown to influence processes related to mood, executive function, sleep, and memory—all of which are linked to core symptoms and associated features of ADHD, such as inattention, impulsivity, deficits in emotional regulation, anxiety, and depression. Centanafadine is a norepinephrine, dopamine, and serotonin reuptake inhibitor.

The researchers (who included investigators from Otsuka) analyzed data from 451 adolescents ages 13 to 17 years who took part the trial. Participants received 164.4 mg or 328.8 mg of centanafadine or placebo once daily for six weeks. The researchers conducted symptom assessments via interviews with a parent/guardian or caregiver of each adolescent (same person throughout the study).

The mean baseline ADHD Rating Scale Version 5 (ADHD-RS-5) total raw score among participants was 37.5. At week six, the mean ADHD-RS-5 total raw score decreased by 15.5, 18.5, and 14.2 points for the centanafadine 164.4-mg, centanafadine 328.8-mg, and placebo groups, respectively. The difference in mean ADHD-RS-5 scores between the centanafadine 328.8 group and placebo at week six was considered statistically significant. The benefits of the 328.8-mg dose over placebo came as early as one week after initiating medication.

Treatment-emergent adverse events occurred in 31.4% of patients in the centanafadine 164.4-mg group, 50.3% in the centanafadine 328.8-mg group, and 23.8% in the placebo group. The most common treatment-emergent adverse events were decreased appetite, nausea, headache, and rash.

For related information, see the Psychiatric Services article “Recent Trends in Medication Treatment for Attention-Deficit Hyperactivity Disorder.”

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VR-Assisted Therapy Can Reduce Severity of Auditory Hallucinations

An immersive, virtual reality (VR)–based psychotherapy can help reduce the frequency and severity of auditory hallucinations in people with schizophrenia, according to a study appearing in Lancet Psychiatry.

Using VR in the treatment of hallucinations allows therapists to digitally embody the heard voice as a three-dimensional avatar, explained Lisa Charlotte Smith, Ph.D., of Copenhagen University Hospital, and colleagues. “This approach facilitates a dialogue between the voice-hearer and the avatar representing a dominant voice, with the therapist assisting the voice-hearer in gaining confidence in standing up to the voice,” they wrote. “The aim is to gradually alter the patient’s response to the avatar, resulting in a more assertive relationship.”

The researchers recruited 271 adults with a schizophrenia spectrum disorder from outpatient clinics across Denmark; all participants had been experiencing auditory hallucinations for at least three months. Participants were randomized to receive either seven sessions of the VR therapy (Challenge-VRT) over 12 weeks or enhanced usual care—which involved flexible assertive community treatment supplemented by seven additional support sessions.

Challenge-VRT is a manualized intervention comprising three phases: reclaiming power over the voice, improving self-worth, and recovery. In the VR sessions, patients engage in dialogues with their avatar, which is voiced by the therapist using a voice transformer; therapists can switch to their natural voice to provide support if needed. The VR dialogues last between two and 20 minutes, with the remainder of each 60-minute session used for preparation and debriefing.

After 12 weeks, participants receiving Challenge-VRT had statistically greater reductions in the severity and frequency of their auditory hallucinations compared with those receiving enhanced usual care. After 24 weeks, hallucination frequency remained lower in the Challenge-VRT group relative to the control group, though there was no longer any difference in hallucination severity.

Smith and colleagues noted that nearly 80% of participants completed the full Challenge-VRT course, and the intervention was generally well tolerated except for a temporary increase in auditory verbal hallucination symptoms during the initial phase. “Few serious adverse events occurred despite the sample consisting of patients who had, on average, experienced voices for 15 years, and for whom hospital admissions and self-harm were not uncommon occurrences,” they wrote.

For related information, see the Psychiatric News article “Virtual Reality Shows Promise in Patients With SMI.”

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Study Derives Optimal Payment Incentives for Contingency Management

Effective contingency management (CM) programs for stimulant and/or opioid use disorder have median inflation-adjusted payment incentives of $128 per week for voucher protocols and $55 per week for prize protocols, according to a report in JAMA Psychiatry.

“These data are intended as starting points or a guide; complex protocols or programs that focus on challenging clinical presentations may need to consider more robust reinforcement schedules,” wrote lead author Carla J. Rash, Ph.D., of the University of Connecticut Health School of Medicine, and colleagues.

CM interventions—such as the California Recovery Incentives Program—make use of monetary incentives (typically gift cards/vouchers or entries for a cash prize drawing) to encourage patient participation in substance abuse treatment. While CM programs have more than 40 years of research support, they are not widely used in the United States.

Rash and colleagues reviewed 112 published CM protocols that involved reinforcement of stimulant- and/or opioid-negative urine drug tests and categorized each protocol as having small, medium, or large effect sizes compared with a non-CM program. They then computed weekly inflation-adjusted incentive payments for voucher- and prize-based protocols.

Of the 112 protocols coded, 49 protocols (44%) reinforced stimulant-negative urine drug tests only, seven protocols (6%) reinforced opioid-negative urine drug tests only, 24 (21%) reinforced both stimulant- and opioid-negative urine drug tests, and 32 protocols (29%) reinforced treatment for additional drugs beyond stimulants and/or opioids (alcohol, benzodiazepines, cannabis, barbiturates, phencyclidine).

Results showed that for the most common protocol length of 12 weeks, the optimal weekly payments in programs that showed moderate to large effect sizes would total about $1,536 ($128/week) for voucher and $660 ($55/week) for prize protocols.

To put these numbers in context, the authors noted that weekly estimated costs for first-line treatments approved by the Food and Drug Administration for opioid use disorder are $126 for methadone treatment, $115 for buprenorphine, and $271 for injectable naltrexone.

“At this time, CM is the treatment with the strongest evidence of efficacy for stimulant use disorders, yet CM remains underused in clinical applications,” they wrote. “In the midst of the continuing opioid and stimulant crisis, our field has the opportunity to invest in evidence-based CM as an effective treatment for substance use disorders.”

For more information, see the Psychiatric News article “Experts Discuss Options for Treating Stimulant Use Disorder.”

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Esketamine Monotherapy Outperforms Placebo for Treatment-Resistant Depression

Esketamine nasal spray monotherapy showed significant and clinically meaningful improvement over placebo in adults with treatment-resistant depression (TRD) starting within 24 hours after initial dosing, according to the results of a study mounted by drugmaker Janssen and published today in JAMA Psychiatry.

Pharmacotherapy for patients with TRD “commonly involves augmentation or combination approaches. However, some of these patients encounter tolerability issues (e.g., weight gain, sexual dysfunction, lethargy, gastrointestinal issues) … which significantly contribute to nonadherence or discontinuation,” wrote Adam Janik, M.D., an investigator with Janssen’s parent company, Johnson & Johnson, and colleagues. “Esketamine monotherapy may expand treatment options for adult patients with TRD by addressing an unmet need of patients experiencing treatment-limiting tolerability concerns and non-response.”

Esketamine was initially approved by the Food and Drug Administration (FDA) in 2019 as an adjunct medication for TRD. Earlier this year, the FDA expanded the indication to allow esketamine as a stand-alone TRD therapy based on the findings of this study.

Janik and colleagues randomized 378 adults with moderate to severe TRD without psychotic features to receive 56 mg esketamine (n= 86), 84 mg esketamine (n = 95), or placebo spray (n = 197) twice weekly. Researchers assessed participants’ changes on the Montgomery-Åsberg Depression Rating Scale (MADRS) over 28 days, after which most participants opted into an open-label study of esketamine (variable dosing) or traditional oral antidepressants for 12 additional weeks.

After 28 days of treatment, the individuals taking either esketamine dose had larger average reductions in their MADRS scores (13 points for the 56 mg group and 14 for the 84 mg group) than those taking placebo (average seven-point reduction). Response and remission rates were also about two to three times as high in the esketamine groups compared with placebo.

In participants who continued esketamine in the 12-week, open-label phase, depressive symptoms remained stable or improved. Adverse events were common among participants given esketamine, most commonly nausea (25%), dissociation (24%), dizziness (22%), and headache (19%).

Limitations of this study include the exclusion of patients with significant psychiatric or medical comorbidities or substance dependence, as well as limited racial and ethnic diversity among participants. Also, the well-known adverse events that are associated with esketamine, such as dissociation and dizziness, led to many participants correctly guessing their treatment, which could have influenced the study results.

For related information, see the Psychiatric News articles “Helping Patients With Treatment-Resistant Depression Reach Remission” and “Disappointing Results for Esketamine as an Add-On After Acute Phase.”

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Intensive Residential Dynamic Psychotherapy Effective for Personality Disorders

A six-month residential program that incorporates intensive short-term dynamic psychotherapy (ISTDP) can produce lasting improvements for individuals with difficult-to-treat personality disorders, according to a study in the American Journal of Psychotherapy.

ISTDP is a therapeutic modality that helps patients understand and confront their inner conflicts, using a strong therapeutic alliance to break down patients’ maladaptive defenses and self-defeating behaviors. This treatment has shown good success in outpatient settings for people with personality disorders, and starting in 1994, the Viersprong hospital in Amsterdam built it into their residential program for treatment-resistant personality disorders, shifting the traditionally individual psychotherapy to a group model—as described in an accompanying article.

Kees L.M. Cornelissen, M.A., a private practice psychotherapist at ISTDP-House in Bergen op Zoom, the Netherlands, and colleagues examined the long-term outcomes of 155 patients who were admitted to the residential ISTDP program between 1995 and 2005. Of these, 107 patients completed questionnaires and interviews in 2006, providing up to 10 years of post-discharge data; for the remaining patients, data previously acquired at discharge and scheduled one- and two-year follow-ups were included.

Personality disorder severity was assessed with the Symptom Checklist-90-Revised, which examines eight domains: agoraphobia, anxiety, hostility, cognitive deficits, depression, interpersonal sensitivity and mistrust, sleeping difficulties, and somatization.

Over the 10-year follow-up, the researchers found that patient symptom scores remained stable after discharge, while overall functioning increased slightly. At residential program admission, 39% of patients had a job, and by year 10 this had increased to 88%. Conversely, the number of patients receiving social welfare benefits dropped from more than 50% at admission to less than 10% at 10 years. The number of patients living with a partner fluctuated during the follow-up but was generally between 30% and 40%.

Residential ISTDP “comes with higher upfront treatment costs than outpatient services,” Cornelissen and colleagues wrote. However, given “the significant costs to both the individual and society associated with personality disorders in terms of functional impairments, disability, and time away from work, administrators should consider the cost-effectiveness of investing in an intensive residential program.”

For related information, see the American Journal of Psychotherapy article “Benefits of Using Intensive Short-Term Dynamic Psychotherapy in Psychiatric Practice.”

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Early Puberty Linked to Increased Risk of Mental Illness

Central precocious puberty (CPP), generally defined as pubertal onset in girls before they are 8 years old and boys before they are 9 years old, may increase the risk of mental illnesses such as depression, anxiety disorders, and attention deficit/hyperactivity disorder (ADHD), according to a study published yesterday in JAMA Network Open.

For some disorders, the risk associated with CPP remained elevated for many years.

Lars Dinkelbach, M.D., of the University of Duisburg-Essen in Germany, and colleagues compared mental health outcomes of 1,094 patients with idiopathic CPP (91.3% female) with those of 5,448 matched controls. They focused on six disorders that commonly emerge during childhood and adolescence: ADHD, anxiety disorders, depression, oppositional defiant disorder/conduct disorder (ODD/CD), self-harm, and substance use disorders. Patients were born between 2000 and 2023 and followed for just under 11 years.

Compared with controls, patients with CPP had a 48% increased risk of receiving a diagnosis of any of the selected mental disorders over follow-up. This included a 45% increased risk of anxiety disorders, a 53% increased risk of ADHD, a 73% increased risk of depression, and a 76% increased risk of ODD/CD. The incidence of depression and ADHD remained higher in youth with CPP for at least eight years after the initial diagnosis.

The researchers noted several possible explanations for the link between CPP and mental illness:

• Physical and social changes resulting from early puberty (e.g., bullying), combined with age-related limitations in coping capacities, may lead to psychological distress.
• Endocrine changes associated with early puberty may lead to disrupted brain maturation or pathologically altered brain activity patterns.
• Substantial preexisting psychological and social burdens may impair coping with early puberty and CPP, thereby exacerbating its negative effects on mental health.

“Early intervention for mental health disorders in children and adolescents can alleviate disease burden and long-term negative psychosocial consequences,” Dinkelbach and colleagues wrote. “Thus, caretakers of patients with CPP should actively explore psychological symptoms and facilitate early intervention to influence lifetime trajectories of this vulnerable patient population positively. Because our findings indicate long-term sequelae of CPP on mental health, caretakers should be vigilant even after normalization of pubertal development.”

For related information, see the Psychiatric News Alert “Childhood Trauma, Early Puberty Associated With Internalizing Symptoms in Girls.”

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Climate Change Significantly Affects Mental Health, Especially Among Younger Adults

More than half of adults (55%) believe climate change is impacting Americans’ mental health, while four in 10 adults say they have personally experienced effects on their mental health, according to a new APA Healthy Minds poll, conducted by Morning Consult on behalf of APA.

More than one-third of poll respondents (35%) worry about climate change on a weekly basis, indicating that for many, this is a persistent source of stress.

Among 10 areas of life possibly affected by climate change, respondents rated their own mental health as the most impacted. A total of 18% said climate change was having a significant impact on their mental health, with 26% saying it was having somewhat of an impact. Other categories noted by at least 40% of respondents included “access to food,” “your physical health,” and “your family.”

The data also highlighted generational and parental divides in perceptions of climate change’s mental health impact. Younger adults ages 18 to 34 were significantly more likely than those 65 or older to report that climate change is affecting their personal mental health (65% versus 30%). Parents (52%) were significantly more likely than non-parents (42%) to report climate change is currently impacting their mental health.

These patterns suggest that those with longer perceived futures—due to either age or the responsibility of raising children—may feel more urgency and emotional burden around climate change, according to an APA statement released in response to the survey.

“As psychiatrists, we see how climate distress and its associated negative emotions affect our patients in various ways, such as grief after a natural disaster or anxiety due to the threat of climate change,” said APA President Theresa Miskimen Rivera, M.D. “These impacts are real; if you’re feeling them, know you’re not alone.”

“Eco-anxiety,” sometimes called climate anxiety, is a chronic fear or worry about the environment and its state, often stemming from concerns about climate change and its impact. Learn more about the connection between climate change and mental health on APA’s website (in English and Spanish).

The Healthy Minds Poll was conducted on March 18-20, 2025, among a sample of 2,208 adults ages 18+ in the United States. Results have a margin of error of plus or minus 2 percentage points.

For related information, see the Psychiatric News article, “What Every Psychiatrist Should Know About the Climate Crisis.”

Also, APA members can check out this month’s free CME course: “Apocalypse Now! Climate Change and its Impact on the Practice of Psychiatry.”

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Screentime Addictive Behaviors in Children Common, Tied to Later Suicidality

There are distinct trajectories of addictive use of social media, mobile phones, and video games in childhood to early adolescence that are linked to suicidality and worse mental health outcomes, according to a study published today in JAMA.

“While most existing research has focused on total screen time, emerging evidence suggests that addictive screen use may be a more salient risk factor for suicidality and mental health in youths,” wrote Yunyu Xiao, Ph.D., of Weill Cornell Medicine, and colleagues. “However, addictive use trajectories among youths have not been well characterized, and how they may relate to suicide-related and mental health outcomes remains largely unknown.”

Xiao and colleagues analyzed data from 4,285 youth enrolled in the longitudinal Adolescent Brain Cognitive Development study. The youth, who were 9 to 10 years old at baseline, completed self-reported surveys on addictive use of social media, mobile phones, and video games (frequency of compulsive use, difficulty disengaging from use, and distress levels when not using) at follow-up years two through four. At year four, children and parents completed assessments of suicidal ideation and behaviors, and parents reported their child’s internalizing (e.g., anxiety, depression) and externalizing (ego, aggression, rule-breaking) symptoms.

The researchers found that nearly half of the participants had high addictive use scores for mobile phones throughout the follow-up, and more than 40% had a high addictive use trajectory for video games. Only 10% of participants had a high addictive use trajectory for social media, but another 31% had addictive use scores that increased over time; 25% of participants also reported an increasing addictive use trajectory for mobile phones.

For both social media and mobile phones, the high and increasing addictive use trajectories were associated with two to three times greater risk of suicidal behaviors and suicidal ideation at year four compared with the low addictive use trajectory. High and increasing addictive use trajectories for social media were further associated with higher internalizing and externalizing symptom scores.

For video games, the high addictive use trajectory was associated with greater risks of suicidal behaviors and suicidal ideation as well as higher internalizing symptoms scores compared with the low addictive use trajectory.

The results underscore “the potential importance of repeated assessment of addictive use of social media and mobile phones among children entering adolescence,” the researchers wrote. “In contrast, video game addictive use followed two trajectories, high and low, which were stable over time, potentially allowing earlier identification of risk without repeated assessment.”

For related information, see the Psychiatric News article “Ask Young Patients About Social Media Use.”

Proposed Medicaid Cuts Would Create Barriers to Care for Millions and Cost Lives

Provisions in H.R. 1 (also known as the One Big Beautiful Bill Act) that aim to cut Medicaid spending threaten several aspects of health—including mental health, according to an analysis in the Annals of Internal Medicine.

Adam Gaffney, M.D., M.P.H., of Cambridge Health Alliance and Harvard Medical School, and colleagues analyzed key provisions of the bill, including:

• Medicaid work requirements mandating that states impose work requirements on nondisabled adults, with specific exemptions
• Reduction of Medicaid provider taxes, which help fund Medicaid by increasing federal assistance via the Federal Medical Assistance Percentage mechanism
• Repeal of a Biden administration rule for Medicaid eligibility determination that simplified enrollment and improved state processes for eligibility determinations (e.g., requiring that states make more efforts to contact beneficiaries before disenrolling them)

Gaffney and colleagues projected the likely effects of these provisions using the House of Representatives Budget Committee’s estimates of savings, analyses by the Congressional Budget Office (CBO), and peer-reviewed studies of the impact of past Medicaid expansions and contractions. After accounting for interactions between provisions, they found that H.R. 1 would:

• Decrease the number of insured adults by 6.8 million
• Decrease the number of adults who self-report good health by 909,720
• Decrease the number of adults who got all needed medical care in the past six months by 1.6 million
• Decrease the number of adults who got all needed medications in the past six months by 1.3 million
• Decrease the number of adults who did not screen positive for depression in the past two weeks by 533,520

Using five different quasi-experimental models, Gaffney and colleagues projected that the bill’s combined Medicaid spending reductions would lead to between 8,241 and 24,604 medically preventable deaths each year.

They added that these estimates may be conservative because they rely on CBO’s assumption that states would replace half of the federal funding shortfall, which would necessitate politically difficult tax increases or cuts to other programs.

“Today, despite its many shortcomings, Medicaid enjoys wide support from the electorate and serves as the foundation of the nation’s health care safety net,” Gaffney and colleagues wrote. “The cuts under consideration, intended to offset the cost of tax cuts that would predominantly benefit wealthier Americans, would strip care from millions and likely lead to thousands of medically preventable deaths.”

For related information, see the Psychiatric News article “Lawmakers Consider Massive Medicaid Cuts.”

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Cannabis Legalization Associated With Increase in Opioid Use Disorder

Legalization of cannabis was associated with small but significant increases in opioid use disorder (OUD) between 2005 and 2022 among patients receiving care in the Veterans Health Administration (VHA), according to a report in JAMA Health Forum. During the same period, states that did not legalize cannabis saw a decrease in OUD.

Zachary Mannes, Ph.D., of Columbia University Irving Medical Center, and colleagues wrote that the results do not support cannabis legalization as a means of reducing the burden of OUD. “These are timely considerations given that the U.S. government has considered cannabis policy reform for the VHA.”

Using VHA electronic health records, the researchers examined yearly state-level rates of OUD among more than 3 million patients who had at least one VHA encounter from January 2005 to December 2022. Patients were considered positive for OUD if they received one or more OUD diagnoses during an outpatient or inpatient encounter at any VA health care facility each year.

Each patient’s state of residence was categorized yearly as having no cannabis laws, medical cannabis laws (MCL), or recreational cannabis laws (RCL). From 2005 to 2022, 37 states and Washington, D.C., enacted an RCL and/or an MCL. (All states with an RCL also enacted an MCL.)

In states that enacted MCL only, OUD prevalence increased among VHA patients from 1.13% in 2005 to 1.19% in 2022, while OUD prevalence decreased from 1.12% to 1.06% in states without cannabis laws. OUD prevalence remained stable in states that enacted an MCL and then an RCL.

Among patients with chronic pain, MCL and RCL enactment was associated with a 0.08% and 0.13% increase in OUD prevalence, respectively. The largest change in OUD prevalence was seen among adults ages 65 to 75 years with chronic pain following RCL enactment—a 0.23% increase. RCL was also associated with a 0.12% increase in OUD prevalence among older adults without chronic pain.

“Cannabis use may be associated with an increased risk of consuming other substances, either by providing more opportunities through access to the same illicit markets or peers who use drugs, or by lowering the threshold for addiction to other substances, including opioids,” the researchers wrote. “Our results should encourage careful regulation of cannabis distribution following legalization and monitoring of OUD symptoms among patients residing in MCL/RCL states, alongside concerted surveillance efforts in older adults who may be particularly susceptible to cannabis and opioid use risks.”

For related information, see the Psychiatric News article “Medical Cannabis Laws Do Not Cut Opioid Death Rates, Study Finds.”

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Stimulant Prescription Via Telehealth Does Not Increase Substance Misuse Risk, Studies Find

Patients who are prescribed stimulants for attention-deficit/hyperactivity disorder (ADHD) via telehealth do not have a greater risk of developing a substance use disorder (SUD) compared with those who receive prescriptions in person, according to a study published this week in The American Journal of Psychiatry (AJP). Patients prescribed via telehealth did have a higher risk of developing a stimulant use disorder, but the authors suggested this may be due to confounding factors.

Vinod Rao, M.D., Ph.D., of Massachusetts General Hospital, and colleagues used electronic health record data to identify 7,944 patients ages 12 and older (57% female, 81% White) who received an initial stimulant prescription for ADHD via telehealth (54% of total) or in-person care (46%) between March 2020 and August 2023.  Overall, 432 patients developed a stimulant use or other SUD.

The patients who initially received their stimulant prescriptions via telehealth did not have a significantly higher risk for developing an SUD. However, those patients were six times more likely than those who received their initial prescription in-person to develop a stimulant use disorder after adjusting for covariates.

“While this finding may be spurious, it may also suggest a bias toward those receiving telehealth care being at higher risk specifically for [stimulant use disorder],” Rao and colleagues wrote. “It may be that in the present analyses, unmeasured patient characteristics associated with a greater likelihood of engaging in telehealth over in-person care (e.g., difficulty accessing reliable transportation) also produce a bias toward the development of [stimulant use disorder].”

This conclusion was supported by a second AJP study published the same day in which Y. Nina Gao, M.D., Ph.D., and Mark Olfson, M.D., M.P.H., of Columbia University, examined data from 63,795 adults who reported having at least one health care visit in the last year in the 2021-2022 National Survey of Drug Use and Health. The survey included information on past-year prescription opioid, benzodiazepine, or stimulant misuse, as well as whether the participants spoke with a health practitioner via telehealth or in-person.

While the unadjusted odds of past-year misuse of prescription opioids, benzodiazepines, and stimulants were between 25% and 46% higher among respondents reporting telehealth use, this association was no longer significant for any of these substances after controlling for participants’ history of misuse of that substance.

“These findings bear on an ongoing policy debate balancing the desire to maintain increased patient access to care while minimizing the potential harms of controlled substance prescribing,” Gao and Olfson wrote. “Although differences in average risk between in-person and telehealth cohorts have sometimes been interpreted negatively as ‘doctor shopping’ (i.e., differential selection across providers), it is important to recognize that some patients with higher risk for substance misuse also struggle to access appropriate general and behavioral health care.”

For related information, see the Psychiatric News Alert “One in 10 Patients Starts Buprenorphine Treatment for OUD via Telehealth.”

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Care Management Improves Outcomes for Adults With First-Time Psychiatric Admission

A brief care management intervention offered to adults following their first psychiatric hospitalization can reduce readmission rates while increasing rates of outpatient aftercare, reports a study published today in Psychiatric Services.

“Although inpatient service is considered a poor outcome of behavioral health care, it provides an opportunity for care management intervention to address medication access, discharge and recovery planning, and connection to aftercare and other resources for continuity of care,” wrote Shari L. Hutchison, M.S., P.M.P., of Community Care in Pittsburgh, and colleagues

While Community Care—a nonprofit behavioral health managed care organization that is part of the University of Pittsburgh Medical Center Insurance Services Division—had already been offering a care management program to Medicaid-enrolled adults with multiple psychiatric admissions, the organization tested an expansion of the intervention to individuals with no prior inpatient history.

Hutchison and colleagues identified 5,140 Medicaid-enrolled adults across 71 facilities in Pennsylvania who had a first-time psychiatric admission in 2022 or 2023. Of this group, 48% received the 10- to 20-minute intervention from a trained care manager, while the remainder did not for various reasons (e.g., coordination issues, early discharge).

Overall, the 30-day psychiatric readmission rate was 9% among those who received the intervention and 11% among those who did not. After adjusting for differences in demographic characteristics and diagnoses between the groups, the researchers calculated that not receiving the intervention increased the odds of readmission by 28%. In addition, 26% of adults who received the care management intervention went to an outpatient appointment within 30 days of discharge, compared with 21% of those who did not.

The reduced readmission rate led to cost savings, with direct expenditures totaling $2.3 million for the intervention group, compared with $2.8 million for the comparison group. The researchers noted that further cost savings from providing this intervention early in an individual’s illness trajectory could be realized in the long term.

“[S]ervices are often prioritized for those with the highest need and costs, such as crisis or residential services targeted to individuals with multiple psychiatric admissions,” the researchers wrote. “Our findings support the necessity of having a diverse array of services within a behavioral health system of care.”

For related information, see the Psychiatric Services article “Care Management for Serious Mental Illness: A Systematic Review and Meta-Analysis.”

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Weekly Pill May Replace Daily Medications for Patients With Schizophrenia

A single, long-acting oral capsule can provide patients with schizophrenia or schizoaffective disorder with a stable dose of medication for one week, according to findings of an open-label study from Lyndra Therapeutics published yesterday in Lancet Psychiatry.

“One of the biggest obstacles in the care of people with chronic illnesses in general is that medications are not taken consistently. This leads to worsening symptoms, and in the case of schizophrenia, potential relapse and hospitalization,” study co-author Leslie Citrome, M.D., M.P.H., of New York Medical College, said in a news release. “Having the option to take medication by mouth once a week represents an important option that can assist with adherence for the many patients who would prefer oral medications versus injectable formulations.”

Citrome and colleagues recruited 83 patients with schizophrenia or schizoaffective disorder from five sites across the United States (25% female, average age 49 years, 81% Black or African American). Before starting the open-label study, participants were given daily, immediate-release risperidone (an antipsychotic) for one week. They then received five of the Lyndra Therapeutics devices, each loaded with a weekly dose of risperidone—either 15 mg or 45 mg.

The device—composed of various polymers—has six arms that are folded inside a capsule about the size of a multivitamin. Once it reaches the stomach, the capsule dissolves and the arms spring out. The device is then too large to exit the stomach, so it remains freely floating and slowly releases risperidone. After about a week, the arms break off and the device remnants pass through the digestive tract.

The participants had risperidone levels at or above the minimum therapeutic concentration across the five-week dosing period relative to corresponding daily dose, and well below the peak concentrations of immediate-release risperidone. This suggests stable drug delivery that may reduce the risk of extrapyramidal side effects, the authors wrote. Similarly, participants’ symptoms remained stable throughout the study period, as assessed with the Positive and Negative Syndrome Scale.

There were some gastrointestinal-related adverse events (such as reflux or constipation) during the first week in which participants took the device, but those decreased over time. Females were more likely to report gastrointestinal-related adverse events than males.

“This really demonstrates … what we had hypothesized a decade ago, which is that a single capsule providing a drug depot within the GI tract could be possible,” study co-author Giovanni Traverso, Ph.D., of the Massachusetts Institute of Technology, said in the news release.

For related information, see the Psychiatric News article “Studies Point to Benefits of Early Treatment With Long-Acting Antipsychotics.”

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Noninvasive Electrical Stimulation Improves Fibromyalgia Symptoms

An at-home electrical stimulation intervention, coupled with exercise and pain education, can significantly reduce fibromyalgia-associated pain, according to results of a clinical trial published yesterday in JAMA Network Open.

Wolnei Caumo, M.D., Ph.D., at the Universidade Federal do Rio Grande do Sul in Porto Alegre, Brazil, and colleagues enrolled 112 adult women ages 18 to 65 with fibromyalgia for their clinical study. Half of the women received a home-based transcranial direct current stimulation (tDCS) headset, which has the anode situated over the left dorsolateral prefrontal cortex (DLPFC) and the cathode placed over the right DLPFC and continuously delivers 2 mA of current. The protocol involved five 20-minute stimulation sessions each week for four weeks.

The other half of the participants received a sham headset that appeared the same but only delivered current for 30-second segments at the beginning, middle, and end of the 20-minute session. All participants also received a chronic pain-management package that included a motivational interview, a suite of educational videos, and an exercise program. At the trial’s start, all women received one sham stimulation session to see if they were prone to experiencing a placebo response.

The women reported their Multidimensional Pain Interference Index (MPII) each week during treatment and again at a three-month follow-up. The MPII measures levels of pain across seven daily activities (general activity, walking, work, mood, enjoyment of life, relationships, and sleep).

After four weeks, MPII scores dropped significantly more in the tDCS group than the sham group across the treatment period and follow-up, with slightly greater decreases seen in placebo responders (49.3% reduction) than non-responders (40.6% reduction). Overall, 62.5% of women in the tDCS group cut their MPII scores in half or more, compared with 37.5% of women in the sham group. Further, nearly 85% of women in the tDCS group reported feeling moderately better or much better after four weeks.

The treatment benefits persisted at the three-month follow-up, though overall MPII scores did rise slightly.

For related information, see the American Journal of Psychiatry article “Spaced Transcranial Direct Current Stimulation for Major Depression” and the accompanying editorial “Spaced Transcranial Direct Current Stimulation for Depression: The Road Less Traveled.”

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