Brief Inpatient CBT Significantly Lowers Future Suicide Attempt Risk, Study Finds.

Adding four sessions of cognitive-behavioral therapy (CBT) to standard suicide prevention treatment at an inpatient hospital can significantly reduce the risk of future suicide attempts, reports a study in JAMA Psychiatry. Among psychiatric inpatients without a substance use disorder (SUD), brief CBT was also found to significantly reduce the risk of hospital readmission.

Gretchen J. Diefenbach, Ph.D., of Yale University School of Medicine, and colleagues randomized 200 adults admitted to a private psychiatric hospital in Connecticut to receive either treatment as usual (n = 106) or usual treatment plus brief CBT (n = 94) during their stay. Study participants—recruited between January 2020 and February 2023—all had a suicide attempt within one week of admission or current suicidal ideation along with a suicide attempt in the past two years. Although adults with current mania or a history of schizophrenia were excluded from participation, individuals with an existing SUD were included, comprising 60% of participants.

Usual treatment entailed 24-hour multidisciplinary care that included safety planning, psychosocial services, and medications as needed. The CBT group also received up to four individual CBT sessions (depending on length of stay) that included components such as developing a crisis response plan, inventorying reasons for living, creating a hope kit, and reducing access to lethal means.

The researchers conducted monthly follow-up assessments with participants upon discharge for six months; overall, 114 participants completed the full six months of assessments.

At six months, participants who had received brief CBT had 60% lower odds of a suicide attempt compared with those only receiving usual treatment. Participants in the CBT group also reported lower levels of suicidal ideation, although only at one and two months post-discharge.

Brief CBT was also associated with 71% decreased odds of psychiatric readmission at six months among participants who did not have an SUD at admission. “These findings are consistent with previous research identifying SUD as a suicide risk factor and poor prognostic indicator,” Diefenbach and colleagues wrote. “Research is needed to disentangle the complex and bidirectional interplay between substance use and its medical, social, and psychiatric correlates to inform the development of SUD-specific treatment enhancements in the future.”

The researchers acknowledged that broad uptake of inpatient CBT is a challenge. “In addition to short lengths of stay, workflows can be chaotic, with frequent, often abrupt changes in schedules and discharge plans,” they wrote. “Dissemination of this treatment protocol may not be possible without substantial hospital investment, for example, by creating new positions for specialist suicide prevention staff, who have been trained to administer the [brief] CBT-inpatient protocol with high fidelity.

“Alternatively, adaptations … such as administration by nonexpert clinicians, utilizing a group format, or integrating the use of technology such as mobile applications, may be needed before widespread uptake can occur.”

For related information, see the Psychiatric News article “Peer Specialists Can Aid in Suicide Prevention.”

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Prescription Amphetamines Pose Dose-Dependent Risk for First-Time Psychosis or Mania

Young people taking prescription amphetamines were nearly three times more likely to develop first-episode psychosis or incident mania than those taking methylphenidate, according to a study issued today by AJP in Advance.

The Food and Drug Administration added warnings to prescription stimulant labels in 2007 after studies showed they increased risk of psychotic or manic symptoms, even among patients with no history of these symptoms. Despite a more than five-fold increase in prescribing rates in the past two decades, “there are currently no published studies to guide prescribers on dose levels and other factors that impact the rare but serious risk,” wrote Lauren V. Moran, M.D., M.P.H., of McLean Hospital in Belmont, Massachusetts, and colleagues.

Moran and colleagues analyzed health records for first-time inpatients aged 16 to 35 years at McLean Hospital between 2005 and 2019. They matched 1,374 individuals who were experiencing initial psychosis or new onset mania with 2,748 admitted with other diagnoses.

After factoring in other substance use, patient psychiatric history, and other variables, the researchers found that patients with any past-month prescription amphetamine use were 2.7 times more likely to develop psychosis or mania than those with no use. Patients taking high doses of amphetamines—defined as >30 mg dextroamphetamine or equivalent (40 mg of mixed amphetamine salts or 100 mg of lisdexamfetamine)—were 5.3 times more likely to have psychosis or mania. Patients aged 23 years or older had higher odds of psychosis or mania than younger patients, possibly due to the higher average amphetamine dose researchers observed in the older group.

Moreover, patients taking prescription amphetamines were 2.85 times more likely to experience incident psychosis or mania than those taking methylphenidate. Those taking methylphenidate did not have increased odds of psychosis or mania than those not taking these medications, researchers noted.

“Our results suggest that prescription amphetamine dose is the most important modifiable factor associated with stimulant-related psychosis or mania…. Our findings suggest that clinicians can mitigate the risk of psychosis or mania by avoiding doses above 30 mg dextroamphetamine equivalents,” Moran and colleagues wrote. “In patients who experience impairment from ADHD symptoms who may benefit from doses above 30 mg dextroamphetamine equivalents, careful monitoring with screening for symptoms of psychosis or mania is critically warranted.

“This is of particular importance given that psychosis and mania are often associated with lack of insight,” the researchers continued. “Symptoms that develop in the context of prescription amphetamine use could emerge without the patient’s awareness, leading to a delay in detection.”

For related information, see the Psychiatric News article “Study Finds Higher Risk of Psychosis With Amphetamines for ADHD.”

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COVID Lockdowns May Have Accelerated Brain Aging in Adolescents, Especially Females

Young females may have experienced significant brain changes as a result of disruptions of social life caused by the COVID-19 pandemic, according to a report in PNAS.

An analysis of MRI images taken before and after the pandemic revealed accelerated thinning in regions of the frontal cortex among a sample of children and adolescents. This thinning was observed in both sexes but was more widespread and of greater magnitude in females.

“As accelerated cortical thinning during brain development is associated with increased risk in the development of neuropsychiatric and behavioral disorders, the findings from this study highlight the importance of providing ongoing monitoring and support to adolescents who experienced the pandemic lockdowns,” wrote Patricia Kuhl, Ph.D., and colleagues at the University of Washington.

The researchers collected MRI data in 2018 from 160 Seattle-area adolescents aged 9, 11, 13, 15, and 17; none of the adolescents had a diagnosis of a developmental or psychiatric disorder or were taking psychotropic medication. The authors collected MRI data again in 2021 and early 2022 from 130 of these youths, now aged 12, 14, 16, 18, and 20.

Kuhl and colleagues used a subset of the pre-COVID-19 MRI data to model the expected change in cortical thickness between the ages of 9 and 17. They then compared this model of normal change over time to the observed cortical thinning of 54 participants who were 12, 14, or 16 during the second MRI scan and whose baseline scans were not used to generate the model.

The comparison revealed widespread cortical thinning throughout the female brain in post-COVID-19 scans, occurring in 30 brain regions associated with social cognition; in males, thinning was limited to two brain regions associated with visual processing of faces. Among females, the magnitude of accelerated thinning was equal to 4.2 years of aging, compared with 1.4 years in males.

The authors noted that accelerated brain development has long been associated with social stress such as deprivation and neglect; they suggested that, for females, peer relationships are vital for the development of self-identity because they rely on these relationships for emotional support more than males. “The effect of the resulting isolation on the needs of male and female adolescents may have been very different, with females perhaps experiencing more stress than males associated with this prolonged isolation,” they wrote.

Kuhl and colleagues concluded: “…[T]hese findings add evidence for the necessity of new public health campaigns to provide support for adolescents and young adults struggling with mental health challenges, as the pandemic lockdowns dramatically increased the incidence of these types of disorders.”

For related information, see the Psychiatric News article “After the Pandemic, What Will the ‘New Normal’ Be in Psychiatry?”

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Cerebrospinal Fluid May Not Be Contained to Cerebrospinal Region

A study published in Science Advances provides evidence that cerebrospinal fluid (CSF) is not contained to the brain and spinal cord—it can potentially travel throughout the nervous system.

“Our results support a contiguous and continuous CSF flow system from the CNS [central nervous system] to the distal ends of peripheral nerves, a function likely integral in sustaining peripheral nerves through delivery of nutrients and removal of waste,” wrote Alexander P. Ligocki, Ph.D., of the University of Florida, and colleagues.

Ligocki and colleagues injected tiny gold particles (about 2 nanometers in size) containing a tracer dye into the lateral ventricles—CSF-filled chambers within the brain—of laboratory mice. While the particles initially dispersed across the brain and spinal cord, within four to six hours they had spread into peripheral nerves such as the trigeminal nerve that controls facial sensations and the sciatic nerve that runs down the back of each leg. The particles were contained in the endoneurium—a fluid-filled sheath of connective tissue that surrounds nerve bundles.

Larger, 15-nanometer gold particles did not escape the central nervous system but collected in the brainstem and spinal cord near the origins of peripheral nerves. The researchers also injected the tiny gold particles into the veins of the mice and did not observe any tracer dye in peripheral nerves, indicating the particles were not passing through the blood-brain barrier and traveling through the blood stream.

“The presence of a contiguous CSF flow route from the CNS along peripheral nerves has far-reaching implications for peripheral nerve health and neuropathologies,” Ligocki and colleagues wrote. They noted, for example, that a continuous flow system may explain why diseases like Alzheimer’s or Parkinson’s can be associated with loss of feeling in the hands or feet—because disturbances in CSF pressure in the brain will spread throughout the body.

“Furthermore, our results suggest that infusion into the CSF compartment may be an efficacious method for direct delivery of drugs and therapeutic agents to peripheral nerves,” the researchers added.

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APA Applauds New Final Rules Strengthening Mental Health Parity

Today, the Biden-Harris administration issued final rules that strengthen the 2008 Mental Health Parity and Addiction Equity Act (MHPAEA) with the goal of improving people’s access to quality mental health and substance use disorder care. Issued by the U.S. Departments of Labor, Treasury, and Health and Human Services, the rules reinforce that insurance plans must ensure that mental health care benefits are no more restrictive than those medical and/or surgical benefits.

“APA has always been a strong advocate for mental health parity, and since its enactment, APA has worked tirelessly to advocate for compliance with and enforcement of the federal parity law,” APA CEO and Medical Director Marketa M. Wills, M.D., M.B.A., said in a statement applauding the rules. "This is a big step forward to hold insurance plans accountable by ensuring the law’s intent is fulfilled and that more individuals will be able to access the mental health and substance use treatment they need.”

Specific provisions in the final rules—which represent the first significant update to the MHPAEA in nearly a decade—include:

Health plans must evaluate their provider networks, out-of-network payment rules, and prior authorization policies, and make changes to reach compliance with the MHPAEA where needed—such as adding more mental health care providers or increasing reimbursement rates.

Health plans cannot use more restrictive prior authorization or other medical management techniques, nor make use of any discriminatory information, to reduce access to mental health and substance use disorder benefits relative to other medical benefits.

Non-federal government health plans (e.g., plans offered to state and local government employees) are no longer exempt from MHPAEA compliance. This change will improve parity for around 120,000 individuals across 200 health plans.

Most of these provisions will take effect on January 1, 2025.

For related information, see the Psychiatric News article “Government Proposes New Rules to Strengthen Parity Law.”

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Researchers Propose Olanzapine and Perphenazine as First-Line Schizophrenia Treatments

Along with aripiprazole and risperidone, olanzapine and perphenazine should be considered first-line antipsychotics for patients with schizophrenia, according to a clinical perspective published in Schizophrenia.

“Clinicians face challenges in balancing efficacy and side effects when prescribing antipsychotics to treatment-naive patients,” wrote Matej Markota, M.D., and colleagues at Mayo Clinic in Rochester, Minnesota. “Existing algorithms approach this issue by assigning high significance to a few side effects, such as weight gain and/or tardive dyskinesia, commonly leading to exclusion of agents such as olanzapine and first-generation antipsychotics (FGAs), respectively, as first-line treatments.”

In the article, Markota and colleagues suggested physicians should focus instead on three overlapping factors:

• Overall efficacy, particularly long-term efficacy since schizophrenia is a disorder requiring long-duration treatment.
• All-cause discontinuation as a surrogate for side-effect burden rather than weighing one or two side effects.
• Mortality risk, which factors in medication effectiveness, discontinuation rate, and long-term burden of reported side effects, such as the cardiovascular implications of excess weight gain.

When considering those factors, the researchers noted that clinical trials have shown olanzapine demonstrates superior efficacy as well as low discontinuation rates compared with risperidone or aripiprazole. Olanzapine does have a high risk of weight gain, but available data does not suggest it increases mortality relative to other medications. Given its demonstrated effects on hostility, the researchers believe olanzapine is a preferred first-line choice for patients for whom aggression may be a concern, with clozapine as a second-line medication.

Meanwhile, perphenazine has typically been overlooked due to the risks of extrapyramidal symptoms like tardive dyskinesia (TD) among first-generation antipsychotics. “However, there is considerable variability in TD risk within FGA and second-generation antipsychotic classes, a nuance frequently ignored by other algorithms,” Markota and colleagues wrote. “Perphenazine has one of the lowest known risks of TD among FGAs.” This medication also has a favorable metabolic and weight gain profile, they noted.

Markota and colleagues stressed that their medication rationale was for a “general” patient: “[W]hen idiographic factors of individuals dictate a different approach, the considerations discussed here should defer to individualized plans, and patients and practitioners should engage in shared decision-making at every step.”

For related information, see the Psychiatric News article “Clozapine Found Most Effective in Patients With Schizophrenia and Conduct Disorder.”

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Researchers Find Lack of Systemic Adverse Event Reporting in Psychedelics Research

About 4% of individuals with a neuropsychiatric disorder had a serious adverse event—including worsening depression, suicidal behavior, psychosis, or convulsions—after being given a “classic” psychedelic as part of a research study, according to a meta-analysis that spanned some 75 years issued by JAMA Psychiatry. The meta-analysis identified no such adverse events among healthy participants; at the same time, tracking of such events should be improved, the study researchers wrote.

“Recording aversive experiences as adverse events is pragmatic and necessary. In particular, the presence and absence of any [adverse events] … such as precipitation of an affective or psychotic illness, persisting perceptual disturbances, and cardiac toxicity, should be clearly reported,” wrote Jared T. Hinkle, M.D., Ph.D., of Johns Hopkins University School of Medicine, and colleagues. “…Our results broadly indicate that while medically or psychiatrically significant adverse events, for example, psychosis [or] suicidality, are relatively rare, these events are often serious when they occur."

Hinkle and colleagues examined 214 clinical or research studies going back to 1951, for which 53% (114 studies) reported analyzable adverse event data. These studies included 1,726 healthy participants, 934 participants receiving outpatient psychiatric care, and 844 participants receiving inpatient psychiatric care; all participants received high doses of one of the four most actively studied psychedelics: LSD (lysergic acid diethylamide), psilocybin, DMT (dimethyltryptamine), or 5-MeO-DMT (5-methoxy-N,N-dimethyltryptamine). All studies involving inpatients were done prior to 1970, researchers noted.

Results were as follows:

• In contemporary research studies (since 2005), there were no reports of deaths by suicide, persistent psychotic disorders, or hallucinogen persisting perception disorders.
• Of 584 outpatient participants administered high-dose psilocybin, three exhibited delayed suicidal behaviors; all three individuals had treatment-resistant depression.
• Reports of other adverse events requiring medical intervention, such as paranoia or headache, were rare.
• Just two serious acute events (within 48 hours of psychedelic effect) were identified in outpatient participants: One person given LSD in a study of anxiety experienced “acute transient anxiety and delusions” refractory to lorazepam, which required olanzapine and overnight observation, and one participant with depression and a history suggestive of orthostasis given DMT experienced a substantial blood pressure drop.

The researchers cautioned that only 29% of contemporary studies with adverse event data reported all adverse events, as opposed to only listing adverse drug reactions. This could explain the lower-than-expected reported rate of certain adverse events—for example, visual hallucinations—among participants. The researchers also noted that individuals with psychotic or manic disorders are typically excluded from contemporary research studies.

“Although psychedelic treatments were initially very well tolerated in participants with psychiatric conditions, the rate of potentially life-threatening delayed adverse events was higher in participants with psychiatric conditions than those without. The reasons for this remain undetermined,” Hinkle, a PGY-2 psychiatry resident at Johns Hopkins Hospital, told Psychiatric News Alert via e-mail. “Also, these data do not generalize to psychedelic use outside of a clinical or research context, so psychiatrists should advise their patients accordingly.”

For more information, see the Psychiatric News article “Psychedelic Use in Psychiatry Demands New Informed Consent Process, Bioethicists Say.”

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Patients Without Psychiatric Illness Likely Not at Risk for Depression, Suicidal Behavior With Semaglutide

People without known major psychiatric illness who are treated with semaglutide for obesity do not appear to be at increased risk for depression or suicidal thinking or behavior compared to patients receiving a placebo, according to a report yesterday in JAMA Internal Medicine.

Semaglutide is a glucagon-like peptide 1 (GLP-1) receptor agonist that has been shown to produce clinically significant weight loss in patients with obesity or Type 2 diabetes. However, both the Food and Drug Administration and the European Medicines Agency have been monitoring the safety of GLP-1 receptor agonists following postmarketing surveillance reports of depression and suicidal ideation in people prescribed these medications, noted Thomas Wadden, Ph.D., of the University of Pennsylvania Perelman School of Medicine, and colleagues.

Wadden and colleagues analyzed pooled data from four phases of the Semaglutide Treatment Effect in People with Obesity (STEP) trial that tested 2.4 mg of semaglutide in patients with obesity. (One phase of the trial also included patients with Type 2 diabetes.). The STEP trial excluded participants who had a history of severe psychiatric illness—such as major depression or schizophrenia—or suicide attempt, as well as individuals who screened for elevated depressive symptoms or suicidal ideation within the past 30 days. The original STEP trial and this secondary analysis were funded by Novo Nordisk A/S, and researchers from the company were involved in this analysis.

The analysis included 3,681 patients (73% female). Across the four trials, only 2.8% of patients treated with semaglutide had a postbaseline Patient Health Questionnaire score of 15 or greater—suggestive of moderately severe or greater symptoms of depression requiring evaluation by a mental health professional—compared with 4.1% of those receiving placebo. Suicidal ideation as assessed by the Columbia–Suicide Severity Rating Scale was less than 1% in all trials, with no differences between treatment groups.

Wadden and colleagues noted that a small number of patients taking semaglutide may experience depression or suicidal thoughts “which may be related to psychosocial complications of obesity or other factors, including life stressors.”

They concluded: “We encourage clinicians to monitor mental health in people with overweight or obesity, including those prescribed semaglutide, 2.4mg, or similar medications. This is essential for ensuring that these individuals obtain the psychiatric care they require to manage anxiety, depression, and related psychiatric complications, which may occur in the presence or absence of weight management interventions.”

In another study published in JAMA Internal Medicine yesterday, Peter Ueda, M.D., Ph.D. at Sweden’s Karolinska Institutet and colleagues analyzed nearly a decade of patient data from Swedish and Danish health registries and found no evidence that GLP-1 RAs increased the risk of suicide death in adults relative to those who took another class of diabetes medications (sodium-glucose cotransporter-2 inhibitors).

For more information, see the Psychiatric News article “Blockbuster Weight Loss Drugs Not Tied to Suicidality, Studies Show.”

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Cannabis Use Linked to Absenteeism at Work

Cannabis use disorder (CUD) and frequent cannabis use are linked to greater absenteeism at work, a study in the American Journal of Preventive Medicine has found.

Kevin H. Yang, M.D., of the University of California, San Diego, and colleagues analyzed data from 46,499 adults who were employed full-time and participated in the National Survey on Drug Use and Health from 2021 to 2022. Participants were asked if they had ever used cannabis and, if yes, how recently. Those who used cannabis in the past month were asked how often. Proxy diagnosis of CUD and CUD severity were determined using standardized items corresponding to DSM-5 criteria. Participants were then asked how many days of work they had missed in the past month because they were sick or injured and how many days of work they had missed because they “just didn’t want to be there.”

Overall, an estimated 15.9% of participants used cannabis in the past month. In addition, 4.0%, 1.6%, and 0.9% met criteria for mild, moderate, and severe CUD, respectively. Participants who used cannabis in the past month had a mean 1.47 days of missed work because of illness or injury, compared with 0.95 days for those who never used cannabis. Participants who used cannabis in the past month had a mean 0.63 days of skipping work compared with 0.28 days for those who had never used cannabis. Individuals who met the criteria for any CUD were more likely than those without CUD to miss or skip work, with the latter showing a stepwise increase as CUD severity increased.

Yang and colleagues wrote that cannabis use has been linked to anxiety, panic attacks, depression, sleep disturbances, respiratory issues, and vehicle accidents, all of which could contribute to increased absenteeism due to illness or injury. They added that individuals who are injured or ill may turn to cannabis for self-medication, potentially exacerbating the cycle of absenteeism.

The researchers noted that cannabis consumption may lead to reduced motivation and cognitive changes, which may partially explain why individuals who use cannabis are more likely to skip work. They added that such associations may be bidirectional, where individuals wanting to skip work may be more inclined to use cannabis because of factors such as boredom.

“These findings underscore the need for targeted interventions, workplace prevention policies, and further research to mitigate the negative consequences of cannabis use on work productivity and overall public health,” Yang and colleagues concluded.

For related information, see the Psychiatric News article “SUDs Cost Employer Health Insurance $35 Billion Per Year.”

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