Efficacy of Adjunctive Infliximab vs Placebo in the Treatment of Adults With Bipolar I/II Depression

作者：Roger S. McIntyre, Mehala Subramaniapillai, Yena Lee, Zihang Pan, Nicole E. Carmona, Margarita Shekotikhina, Joshua D. Rosenblat, Elisa Brietzke, Joanna K. Soczynska, Victoria E. Cosgrove, Shefali Miller, E. Grace Fischer, Nicole E. Kramer, Kiley Dunlap, Trisha Suppes, Rodrigo B. Mansur · 发表于：JAMA Psychiatry · 年份：2019 · DOI：10.1001/jamapsychiatry.2019.0779 · 被引用次数：196 · 研究领域：Tryptophan and brain disorders、Stress Responses and Cortisol、Macrophage Migration Inhibitory Factor

Importance: To our knowledge, no study has previously evaluated whether individuals with bipolar depression enriched a priori on the basis of biochemical and/or phenotypic immuno-inflammatory activation would differentially respond to an anti-inflammatory agent for the treatment of depressive symptoms. Objective: To assess the antidepressant efficacy of adjunctive infliximab, a monoclonal antibody targeting tumor necrosis factor, in adults with bipolar I and bipolar II depression and inflammatory conditions. Design, Setting, and Participants: This 12-week, randomized, double-blind, placebo-controlled, parallel-group trial of 60 participants was conducted at 2 outpatient tertiary care sites in Canada and the United States. Eligible adults (aged 18-65 years) met DSM-5-defined criteria for bipolar I or bipolar II depression and exhibited pretreatment biochemical and/or phenotypic evidence of inflammatory activation. Participants were enrolled between October 1, 2015, and April 30, 2018. Data analysis was performed from May 1 through July 31, 2018, using modified intent-to-treat analysis. Interventions: Patients were randomized to receive 3 intravenous infusions of infliximab therapy or placebo at baseline and at weeks 2 and 6 of the 12-week study. Main Outcomes and Measures: The primary efficacy outcome was baseline-to-end point (ie, week-12) change in Montgomery-Asberg Depression Rating Scale (MADRS) total score. History of childhood maltreatment, as assessed by the Childhood T...