Effect of symptom severity on efficacy and safety of aripiprazole adjunctive to antidepressant monotherapy in major depressive disorder: a pooled analysis.

BACKGROUND: There is a paucity of evidence for outcome predictors in patients with major depressive disorder (MDD) not responding to initial antidepressant therapy (ADT). This post-hoc analysis evaluated whether MDD severity affects response to adjunctive aripiprazole. METHODS: Data from 3 randomized, double-blind, placebo-controlled trials of adjunctive aripiprazole in adults with MDD and inadequate response to 1 to 3 ADT trials were pooled and stratified based on Montgomery-Åsberg Depression Rating Scale (MADRS) total score (mild, ≤24; moderate, 25-30; severe, ≥31). Treatment differences in change in MADRS total score and rates of response (≥50% MADRS improvement) and remission (response with MADRS total score ≤10) were analyzed at endpoint. Adverse events were assessed within each subgroup. RESULTS: Aripiprazole produced greater improvement than placebo in the MADRS total score regardless of MDD severity at baseline (between-treatment difference [95% CI]: mild, -2.5 [-4.0 to -1.1]; moderate, -3.2 [-4.9 to -1.6]; severe, -4.5 [-6.8 to -2.2]). Compared with placebo, adjunctive aripiprazole increased the likelihood of response in all subgroups (risk ratio [95% CI]: mild, 1.50 [1.15, 1.95]; moderate, 1.51 [1.09, 2.11]; severe, 1.95 [1.23, 3.10]). Common treatment-emergent adverse events included akathisia and restlessness. LIMITATIONS: The original studies were not designed to assess the efficacy of adjunctive aripiprazole by baseline severity, and this post-hoc analysis was not powered to evaluate differences in severity subgroups. CONCLUSIONS: In patients who failed to respond to initial ADT, adjunctive aripiprazole was more effective than placebo in mild, moderate, and severe MDD strata. CLINICAL TRIAL REGISTRATION: ClinicalTrial.gov: NCT00095823, NCT00105196, and NCT00095758.

Metabolic adverse events in patients with mental illness treated with antipsychotics: a primary care perspective.

BACKGROUND: Individuals with mental illness are at a higher risk of medical mortality than the general population, primarily due to an increased risk of cardiovascular disease. There are a number of modifiable metabolic risk factors associated with some atypical antipsychotics that warrant careful monitoring and treatment in both psychiatric and primary care practice if the risk of cardiovascular disease is to be effectively reduced. DATA SOURCES: Previous guidelines have focused on awareness of metabolic risk factors in psychiatry, yet few articles have appeared in the primary care-focused journals. We present pragmatic guidelines that focus on monitoring metabolic abnormalities in primary care based on established guidelines, including joint recommendations of the American Diabetes Association, the American Psychiatric Association, the American Association of Clinical Endocrinologists, and the North American Association for the Study of Obesity, and the Mount Sinai conference. DATA SYNTHESIS: All patients receiving atypical antipsychotic agents associated with metabolic adverse events should be routinely monitored for weight gain and abnormalities in blood glucose and lipid levels. Effective communication and collaboration between mental health and primary care services and better access to primary care screening and treatment for individuals with mental health problems are needed. CONCLUSION: There is a clear need for awareness among primary care physicians, particularly as metabolic effects of atypical antipsychotics such as blood pressure and glucose and lipid levels are possibly best monitored in a primary care setting.