Adjunctive infliximab, an anti-inflammatory agent, did not significantly decrease depressive symptoms compared with placebo in adults with bipolar depression in a 12-week, randomized trial.
Prior evidence suggests that certain anti-inflammatory agents may be efficacious in some patients with bipolar disorder, Roger S. McIntyre, MD, from the Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, and colleagues wrote in JAMA Psychiatry.
“To our knowledge, no study has previously evaluated whether individuals with bipolar disorder 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,” they wrote.
Researchers evaluated the antidepressant efficacy of adjunctive infliximab (Remicade, Janssen) in 60 adults with bipolar I or bipolar II depression and inflammatory conditions. The patients were randomized to receive three IV infusions of infliximab therapy or placebo at baseline, week 2 and week 6.
McIntyre and colleagues measured change in the Montgomery-Asberg Depression Rating Scale (MADRS) total score from baseline to week 12 (primary efficacy outcome). For secondary outcomes, they performed exploratory analyses to determine the moderating effects of baseline C-reactive protein (CRP) level, illness severity and course, and history of childhood maltreatment as measured by the Childhood Trauma Questionnaire (CTQ).
In total, 29 adults received infliximab and 31 received placebo. Analysis revealed a significant treatment × time interaction only at week 2 (RR = 0.86; 95% CI, 0.75-0.98), with adults receiving infliximab demonstrating lower depressive symptom severity at compared with those receiving placebo. However, there was no effect at week 6 (RR = 0.87; 95% CI, 0.67-1.13) or week 12 (RR = 1.09; 95% CI, 0.8-1.5).
Secondary analysis revealed infliximab-treated participants with childhood history of physical abuse had greater reductions in MADRS total score (2 = 12.2; P = .02) and higher response rates (2 = 4.05; P = .04) than placebo-treated participants. Specifically, higher levels of past physical abuse were linked to higher response rates among infliximab-treated patients at week 8 (RR = 0.95; 95% CI, 0.91-0.99) and week 12 (RR = 0.88; 95% CI, 0.81-0.96), according to the results.
“The results herein have conceptual and clinical implications ... Clinically, the results of our study support the stratification of participants by history of childhood maltreatment within studies that broadly aim to determine whether anti-inflammatory agents are potentially symptom mitigating or disease modifying in bipolar disorder,” McIntyre and colleagues wrote.
This study failed to show that a biomarker-guided treatment “would have an efficacy advantage,” Michael Berk, MD, PhD, of Deakin University School of Medicine, Australia, and colleagues wrote in a related editorial.
“The promise of precision psychiatry, that it would be possible to improve clinical outcomes by selecting treatments tailored to an individual’s neurobiology, psychology, or sociology, remains an attractive yet elusive goal,” they wrote.
“Nonetheless, this study leaves open questions: which inflammatory biomarkers researchers should use to stratify participants, what is the optimal cut point for any biomarker to define inflammation (or should it be analyzed as a continuous variable), and what anti-inflammatory strategies, if any, should they investigate?” – by Savannah Demko
Disclosure: McIntyre reports receiving grants from Stanley Medical Research Institute, receiving grants from the Canadian Institutes of Health/Research/Global Alliance for Chronic Diseases/Chinese National Natural Research Foundation, and receiving speaking/consultation fees from Allergan, Janssen, Lundbeck, Minerva, Neurocrine, Otsuka, Pfizer, Purdue, Shire, Sunovion and Takeda. Please see the full study and editorial for all other authors’ relevant financial disclosures.