Secondary Mania induced by TNF‐α inhibitors: A systematic review

A growing number of studies support a bidirectional relationship between inflammation and bipolar disorders. Tumor necrosis factor‐α (TNF‐α) inhibitors have recently attracted interest as potential therapeutic compounds for treating depressive symptoms, but the risk for triggering mood switches in p...

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Bibliographic Details
Published in:Psychiatry and clinical neurosciences 2022-01, Vol.76 (1), p.15-21
Main Authors: Miola, Alessandro, Dal Porto, Veronica, Meda, Nicola, Perini, Giulia, Solmi, Marco, Sambataro, Fabio
Format: Article
Language:English
Subjects:
Affective disorders
Bipolar disorder
bipolar disorders
Case reports
Cohort Studies
disease‐modifying antirheumatic drugs
Etanercept
Humans
immune system
Infliximab
Infliximab - adverse effects
Mania - chemically induced
manic switch
Mental disorders
Meta-analysis
Monoclonal antibodies
Mood
Patients
Review
Systematic review
TNF inhibitors
Tumor Necrosis Factor Inhibitors - adverse effects
Tumor Necrosis Factor-alpha - antagonists & inhibitors
Tumor necrosis factor-TNF
Tumor necrosis factor-α
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Summary:A growing number of studies support a bidirectional relationship between inflammation and bipolar disorders. Tumor necrosis factor‐α (TNF‐α) inhibitors have recently attracted interest as potential therapeutic compounds for treating depressive symptoms, but the risk for triggering mood switches in patients with or without bipolar disorders remains controversial. Thus, we conducted a systematic review to study the anti‐TNF‐α medication‐induced manic or hypomanic episodes. PubMed, Scopus, Medline, and Embase databases were screened for a comprehensive literature search from inception until November 2020, using The Preferred Reporting Items for Systematic Reviews and Meta‐Analyses guidelines. Out of the initial 75 references, the screening resulted in the inclusion of four case reports (each describing one patient) and a cohort study (in which 40 patients out of 7600–0.53% – experienced elated mood episodes after infliximab administration). Of these 44 patients, 97.7% experienced a manic episode and 2.3% hypomania. 93.2% of patients had no history of psychiatric disorder or psychotropic treatment. Only 6.8% had a history of psychiatric disorders with the affective spectrum (4.6% dysthymia and 2.3% bipolar disorder). The time of onset of manic or hypomanic symptoms varied across TNF‐α inhibitors with an early onset for Infliximab and a later onset for Adalimumab and Etanercept. These findings suggest that medications targeting the TNF‐α pathway may trigger a manic episode in patients with or without affective disorders. However, prospective studies are needed to evaluate the relative risk of such side effects and identify the population susceptible to secondary mania.
ISSN:1323-1316
1440-1819
DOI:10.1111/pcn.13302