Efficacy of adjunctive infliximab vs. placebo in the treatment of anhedonia in bipolar I/II depression
We investigated the efficacy of tumour necrosis factor (TNF) a 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 a 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) 48 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 x time interaction effect: kh2=7.15,df=2,p=0.03) Anti anhedonic efficacy was moderated by baseline plasma levels of TNF a and sTNFR1, but not by changes in TNF a 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.
Brain, Behavior, and Immunity