Efficacy of Adjunctive Infliximab vs Placebo in the Treatment of Adults With Bipolar I/II Depression: A Randomized Clinical Trial.
Level 2 - randomized trial
Individual randomized double-blind placebo-controlled trial
PubMed 31066887 · doi:10.1001/jamapsychiatry.2019.0779
What was done
A 12-week, randomized, double-blind, placebo-controlled, parallel-group trial was conducted across 2 outpatient tertiary care sites in Canada and the United States. Sixty adults aged 18 to 65 years with DSM-5 bipolar I or II depression and pretreatment biochemical or phenotypic evidence of inflammatory activation were randomized to receive 3 intravenous infusions of infliximab (n = 29) or placebo (n = 31) at baseline, week 2, and week 6. The primary outcome was change in Montgomery-Asberg Depression Rating Scale (MADRS) total score from baseline to week 12, evaluated using a modified intent-to-treat analysis. Exploratory secondary analyses evaluated treatment interactions with childhood maltreatment history assessed via the Childhood Trauma Questionnaire.
What was found
At week 12, the reduction in MADRS depressive symptom severity did not significantly differ between infliximab and placebo (relative risk, 1.09; 95% CI, 0.80–1.50; df = 1; P = .60), although an overall treatment × time interaction across the 12-week period was noted (χ² = 10.33; P = .04). In secondary exploratory analyses, a significant treatment × time × childhood maltreatment interaction was observed: participants with a history of physical abuse receiving infliximab showed greater MADRS reductions (χ² = 12.20; P = .02) and higher response rates (≥50% MADRS reduction; χ² = 4.05; P = .04).
Why it matters
Despite pre-selecting patients with baseline inflammatory activation, tumor necrosis factor inhibition with infliximab failed to demonstrate overall antidepressant efficacy in bipolar depression. The findings challenge the broad application of anti-inflammatory monotherapies or adjuncts without further mechanistic or subpopulation stratification.
Limits
The study had a small sample size (n = 60), which limited statistical power for detecting modest effect sizes. The positive findings in patients with childhood physical abuse stem from exploratory secondary subgroup analyses and require prospective replication. The cohort was predominantly female (71% in the infliximab group, 87% in the placebo group) and restricted to outpatient tertiary care settings, limiting generalizability.
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- supports Studies have investigated using TNF-alpha blockers as a treatment for depression.