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

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

doi:10.1016/j.bbi.2020.04.063

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

Brain Behav Immun. 2020 Aug:88:631-639. doi: 10.1016/j.bbi.2020.04.063. Epub 2020 May 4.

Authors

Affiliations

¹ Institute of Medical Science, University of Toronto, Toronto, ON, Canada; Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, ON, Canada.
² Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, ON, Canada; Department of Psychiatry, University of Toronto, Toronto, ON, Canada.
³ Psychiatry; Centre for Neuroscience Studies, Queen's University, Kingston, ON, Canada.
⁴ Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, ON, Canada; Department of Psychology, Ryerson University, Toronto, ON, Canada.
⁵ Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, ON, Canada.
⁶ Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, ON, Canada; Department of Psychiatry, University of Ottawa, Ottawa, ON, Canada.
⁷ Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA, USA; VA Palo Alto Health Care System, Palo Alto, CA, USA.
⁸ Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA, USA.
⁹ Institute of Medical Science, University of Toronto, Toronto, ON, Canada; Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, ON, Canada; Department of Psychiatry, University of Toronto, Toronto, ON, Canada; Department of Pharmacology, University of Toronto, Toronto, ON, Canada; Brain and Cognition Discovery Foundation, Toronto, ON, Canada. Electronic address: Roger.McIntyre@uhn.ca.

PMID: 32380271
DOI: 10.1016/j.bbi.2020.04.063

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.

Keywords: Anhedonia; Bipolar disorder; Depression; Mood disorders; Treatment efficacy.

Publication types

Randomized Controlled Trial
Research Support, Non-U.S. Gov't

MeSH terms

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

Substances

Infliximab

Associated data

ClinicalTrials.gov/NCT02363738

Grants and funding

K08 CA237528/CA/NCI NIH HHS/United States