Journal Digest

High Initial Antidepressant Dosages in Youth May Raise Self-Harm Risk

High initial dosages of antidepressants appear to increase risk of deliberate self-harm in children and young adults, according to data from a study published in JAMA Internal Medicine. Researchers from the Harvard School of Public Health examined the relationship between suicidal behavior and antidepressant dosage, and whether such a relationship, if it exists, is dependent on a patient’s age. The study assessed data from 162,625 people—aged 10 to 64—with depression who initiated antidepressant therapy with a selective serotonin reuptake inhibitor at “modal” (most prescribed dosage on average) or higher than modal dosages.

The analysis showed that participants aged 24 and younger who initiated antidepressant therapy at high doses were twice as likely to exhibit suicidal behaviors than were their age-matched counterparts who received modal doses—corresponding to one additional event of deliberate self-harm for every 150 patients treated with high-dose antidepressant therapy. The authors found no dose-dependent risk for suicidal behavior among adults aged 25 to 64.

In a commentary, David Brent, M.D., a professor of psychiatry, pediatrics, and epidemiology at the University of Pittsburgh who was not involved in the study, noted that “while initiation at higher than modal doses of antidepressants may be deleterious, this study does not address the effect of dose escalation. . . . Studies on the impact of dose escalation in the face of nonresponse remain to be done—there are promising studies that suggest in certain subgroups that dose escalation can be of benefit.” Brent concluded that these findings “add further support to current clinical recommendations to begin treatment with lower antidepressant doses.”

Study Identifies Genetic Biomarker That May Contribute to OCD

Researchers from Johns Hopkins University School of Medicine provided some insight into factors that may underlie obsessive-compulsive disorder (OCD), which affects about 2 percent of the U.S. population, according to the National Institute of Mental Health.

Gerald Nestadt, M.D., Ph.D., director of the OCD program at Johns Hopkins, and colleagues reported in Molecular Psychiatry that they conducted a genomewide association study to identify genetic biomarkers associated with OCD. The researchers scanned the genomes of more than 1,400 individuals with OCD and approximately 1,000 close relatives of other people with OCD (as a control group). The study results showed that patients with OCD expressed a particular biomarker located near the protein tyrosine phosphokinase gene—a genetic region that previous research suggested is important in the pathology of OCD.

“OCD research has lagged behind other psychiatric disorders in terms of genetics,” stated Nestadt. “We hope this interesting finding brings us closer to making better sense of it.”

“If this finding is confirmed,” he said, “we might ultimately be able to identify new drugs that could help people with this often disabling disorder, [for whom] current medications work only 60 percent to 70 percent of the time.”

Lower Hippocampus Volume Seen in Patients With Psychosis

The Bipolar-Schizophrenia Network on Intermediate Phenotypes—consisting of institutions that include Harvard University, Wayne State University, and the University of Texas Southwestern—conducted a neuroimaging study in 549 patients with schizophrenia, schizoaffective disorder, or bipolar disorder with psychosis to evaluate hippocampal volume in individuals with psychosis and the consequences of hippocampal volume as it relates to the severity of the psychosis. The participants were compared with 337 healthy volunteers.

The results, published in JAMA Psychiatry, showed that volume in the hippocampus was significantly reduced in all three groups of patients with psychotic disorders when compared with that of controls. Reduced hippocampal volumes were correlated with worsened psychosis severity, declarative memory, and overall cognitive performance.

“The causal mechanisms underlying psychotic symptoms are not well known,” Matcheri Keshavan, M.D., a professor of psychiatry at Harvard Medical School, told Psychiatric News in an interview. “The findings in this study point to the hippocampus . . . as a critical node on the network of brain regions that underlie the generation of psychotic symptoms such as delusions and hallucinations. Such understanding can help clinicians explain the nature of psychotic illnesses to patients and [their] families.” Keshavan concluded that more studies investigating the consequences of physiological and biochemical alterations in the hippocampus “are critically needed.”

Awareness of E-Cigarettes’ Potential Harm Increases

A recent study in the American Journal of Preventive Medicine reports that as awareness of e-cigarettes increases, so does skepticism about these products.

A national survey of 3,630 adults found that 77 percent have heard of e-cigarettes—far from the 16 percent that was reported five years ago. Not only was an increase in e-cigarette awareness noticed, but the survey found that there was a 19 percent drop—from 84 percent to 65 percent—in the perception of e-cigarettes being less harmful than regular cigarettes among current smokers.

The authors noted that “the rise in awareness of e-cigarettes could reflect sharp increases in advertising expenditures by manufacturers . . . and [the] presence in popular media.” They urged health care and public health professionals to continue to “scrutinize the nature of marketing activities and media coverage of e-cigarettes . . . and how these factors may influence e-cigarette use and smoking prevalence in the U.S. population.”

Naltrexone and Acamprosate More Effective in Treating Alcohol Addiction

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Several medications are available to help people with alcohol use disorder (AUD) maintain abstinence or reduce drinking, but the amount of information available on the efficacy of such medications for AUD may be too cumbersome for providers to digest, according to researchers from the University of North Carolina at Chapel Hill (UNC).

Scientists at the Evidence-based Practice Center and Bowles Center of Alcohol Studies at UNC conducted a systematic review of 122 randomized, controlled trials to assess the benefits and harms of medications—approved and unapproved by the Food and Drug Administration—for adults with AUD. The results, published in JAMA, showed acamprosate and naltrexone to have the best evidence for maintaining abstinence from drinking and reducing days of heavy drinking. As for medications used off-label for AUD, there were moderate improvements in some drinking outcomes for topiramate and nalmefene.

James Garbutt, M.D., senior author of the study and a professor of psychiatry at UNC, commented, “This work expands upon the growing evidence that medications can play a valuable role in the treatment of alcohol use disorders. We are hopeful that this information will encourage clinicians to strongly consider these medications and that those individuals will gain awareness that there are medications that can help them to stop or significantly reduce their alcohol use.”