Efficacy of adjunctive infliximab vs. placebo in the treatment of anhedonia in bipolar I/II depression.

Abstract

We investigated the efficacy of tumour necrosis factor (TNF)-α antagonist infliximab on a measure of anhedonia amongst individuals with bipolar I/II depression (ClinicalTrials.gov identifier NCT02363738). Adults (ages 18-65) with bipolar I/II disorder currently experiencing a major depressive episode with a higher probability of inflammatory activity (i.e., meeting one or more of the following inflammatory/metabolic criteria: obesity and dyslipidemia/hypertension, daily cigarette smoking, diabetes mellitus, migraine, inflammatory bowel disease, and/or C-reactive protein level of ⩾5 mg/L) were enrolled in a double-blind, 12-week clinical trial of adjunctive infliximab (5 mg/kg) and saline control, which were administered at weeks 0, 2, and 6. The primary outcome measure for the present secondary analysis was change in the Snaith-Hamilton Pleasure Scale (SHAPS) total score between placebo- and infliximab-treated subjects from baseline to weeks 6 and 12. Plasma concentrations of TNF-α and soluble TNF receptors (sTNFR) 1 and 2 were assessed at weeks 0, 2, 6, and 12. Sixty eligible adults received treatment with infliximab (n=29) or placebo (n=31); 47 subjects completed the study (infliximab: n=21, placebo: n=26). Overall, infliximab-randomized subjects exhibited significantly larger increases in SHAPS total score, denoting greater reductions in anhedonic symptoms, when compared to placebo-randomized subjects (treatment × time interaction effect: χ2=7.15,df=2,p=0.03). Anti-anhedonic efficacy was moderated by baseline plasma levels of TNF-α and sTNFR1, but not by changes in TNF-α or sTNFR1 concentrations. Baseline and changes in sTNFR2 concentrations did not moderate anti-anhedonic efficacy. Infliximab significantly improved a measure of anhedonia relative to placebo in adults with bipolar I/II depression at week 6; intervention efficacy was not sustained 6 weeks after the final infusion.

• Authors: Yena Lee, Rodrigo B Mansur, Elisa Brietzke, Nicole E Carmona, Mehala Subramaniapillai, Zihang Pan, Margarita Shekotikhina, Joshua D Rosenblat, Trisha Suppes, Victoria E Cosgrove, Nicole E Kramer, Roger S McIntyre
• Journal: Brain, behavior, and immunity (Brain Behav Immun) Vol. 88 Pg. 631-639 (08 2020) ISSN: 1090-2139 [Electronic] Netherlands
• PMID: 32380271 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2020 Elsevier Inc. All rights reserved.

Chemical References

• Infliximab

Topics

• Adolescent
• Adult
• Aged
• Anhedonia
• Bipolar Disorder (drug therapy)
• Depression
• Depressive Disorder, Major (drug therapy)
• Double-Blind Method
• Humans
• Infliximab (therapeutic use)
• Middle Aged
• Treatment Outcome
• Young Adult