American Journal of Psychiatry Recognized for Important Studies Published in 2016

Two prestigious institutions have recognized the American Journal of Psychiatry (AJP) for publication of outstanding research that informs and improves clinicians’ practice of psychiatry by enhancing assessment of patients or improving treatment options. They are the New England Journal of Medicine (NEJM) Journal Watch Psychiatry and the Brain and Behavior Research Foundation.

Both listed 10 studies that they thought were the most significant in 2016. Two AJP articles were selected by NEJM Journal Watch Psychiatry, and three were selected by the Brain and Behavior Research Foundation. AJP had the highest number of publications on both lists.

“Providing reliable, up-to-date information for clinicians and their patients is the most important role of the American Journal of Psychiatry,” said AJP Editor Robert Freedman, M.D. “Therefore, the Editorial Board, our authors, and I take special pride in receiving top recognition this year from both NEJM Journal Watch Psychiatry and the Brain and Behavior Research Foundation for bringing our readers the highest quality information that can guide their practice now and in the future.”

These are the two reports selected by NEJM Journal Watch Psychiatry:

• “The Risk of Treatment-Emergent Mania With Methylphenidate in Bipolar Disorder” by Alexander Viktorin, Ph.D., et al.; October 3, 2016.

Using linked Swedish national registries, the authors identified 2,307 adults with bipolar disorder who initiated therapy with methylphenidate between 2006 and 2014. The cohort was divided into two groups: those with and those without concomitant mood-stabilizing treatment. They compared the rate of mania (defined as hospitalization for mania or a new dispensation of stabilizing medication) 0-3 months and 3-6 months after medication start following nontreated periods.

Patients on methylphenidate monotherapy displayed an increased rate of manic episodes within three months of medication initiation, with similar results for the subsequent three months. By contrast, for patients taking mood stabilizers, the risk of mania was lower after starting methylphenidate.

“This is clinically important given that up to 20 percent of people with bipolar disorder suffer from comorbid ADHD,” the authors wrote.

• “Efficacy and Safety of Antidepressants Added to Antipsychotics for Schizophrenia: A Systematic Review and Meta-Analysis” by Bartosz Helfer, M.Sc., et al.; September 2016.

The authors searched multiple databases and previous publications through June 2015 to identify all randomized, controlled trials of any add-on antidepressants compared with placebo or no-treatment in schizophrenia. They examined depressive and negative symptoms (primary outcomes), overall symptoms, positive symptoms, side effects, exacerbation of psychosis, and responder rates.

Analysis of primary outcomes (depressive and negative symptoms) suggests small, beneficial effects of adjunctive antidepressants. “It would appear that this augmentation can be accomplished with a low risk of exacerbation of psychosis and adverse effects,” the authors stated.

The Brain and Behavior Research Foundation selected these reports:

• “Opioid Modulation With Buprenorphine/Samidorphan as Adjunctive Treatment for Inadequate Response to Antidepressants” by Maurizio Fava, M.D., et al.; May 2016.

The researchers found that buprenorphine/samidorphan in combination is a novel and promising candidate for treatment of major depressive disorder for patients who have an inadequate response to standard antidepressants. Samidorphan is an opioid antagonist included to block those effects of buprenorphine that are associated with its addictive potential.

Participants were randomly assigned to receive adjunctive treatment with

2 mg/2 mg of buprenorphine/samidorphan (the 2/2 dosage group), 8 mg/8 mg of buprenorphine/samidorphan (the 8/8 dosage group), or placebo. Antidepressant effect was measured based on change from baseline to the end of four weeks of treatment on the 17-item Hamilton Rating Scale for Depression, the Montgomery-Åsberg Depression Rating Scale, and the Clinical Global Impressions-Severity scale.

Compared with the placebo group, the 2/2 dosage group had significantly greater improvements across the three depression outcome measures. Overall, the buprenorphine/samidorphan combinations were well tolerated, and there was no evidence of opioid withdrawal on treatment discontinuation.

• “An Individualized Risk Calculator for Research in Prodromal Psychosis” by Tyrone D. Cannon, Ph.D., et al., and its companion article, “Personalized Prediction of Psychosis: External Validation of the NAPLS-2 Psychosis Risk Calculator With the EDIPPP Project” by Ricardo E. Carrión, Ph.D., et al.; October 2016.

Cannon and colleagues described an “individualized risk calculator for psychosis,” using data from the second phase of the North American Prodrome Longitudinal Study (NAPLS-2). The calculator is designed to test the risk for conversion to psychosis of newly identified high-risk patients. Predictors were chosen a priori based on a review of the literature on psychosis risk prediction in clinical high-risk samples.

The study subjects were 596 clinical high-risk participants from NAPLS-2 who were followed up to the time of conversion to psychosis or last contact (up to two years). The two-year probability of conversion to psychosis was 16 percent. Higher levels of unusual thought content and suspiciousness, greater decline in social functioning, lower verbal learning and memory performance, slower speed of processing, and younger age at baseline each contributed to individual risk for psychosis. Stressful life events, trauma, and family history of schizophrenia were not significant predictors.

The authors noted that the predictive ability of the psychosis risk calculator based on NAPLS-2 data is in the range of values for established calculators in use for cardiovascular disease and cancer recurrence risk.

Carrion and colleagues validated the NAPLS-2 psychosis risk calculator externally using an independent sample of patients at clinical high risk for psychosis collected as part of the Early Detection, Intervention, and Prevention of Psychosis Program. “The data reported in this study have shown that the performance of the NAPLS-2 psychosis risk calculator, available on the Internet and incorporating a set of theoretically derived risk factors, can be replicated in a separate, independently collected clinical high-risk population,” Carrion and colleagues wrote.

• “Neurometabolic Disorders: Potentially Treatable Abnormalities in Patients With Treatment-Refractory Depression and Suicidal Behavior” by Lisa A. Pan, M.D., et al.; August 13, 2016.

The authors conducted a case-control, targeted, metabolomic evaluation of 33 adolescent and young adult patients with well-characterized histories of treatment-refractory depression (at least three maximum-dose, adequate-duration medication treatments) and 16 healthy comparison subjects. Plasma, urine, and cerebrospinal fluid (CSF) metabolic profiling were performed by coupled gas chromatography/mass spectrometry and high-performance liquid chromatography electrospray ionization tandem mass spectrometry.

CSF metabolite abnormalities were identified in 21 of the 33 participants with treatment-refractory depression. Cerebral folate deficiency (n=12) was most common, with normal serum folate levels and low CSF 5-methyltetrahydrofolate (5-MTHF) levels. All patients with cerebral folate deficiency, including one with low CSF levels of 5-MTHF and tetrahydrobiopterin intermediates, showed improvement in depression symptom inventories after treatment with folinic acid. None of the healthy comparison subjects had a metabolite abnormality. ■