TNF-α inhibitors and psychiatric adverse drug reactions in the spectrum of bipolar (manic) or psychotic disorders: Analysis from the French pharmacovigilance database

Summary Objective This study aimed to describe reports of psychiatric adverse drug reaction (ADR) in the spectrum of bipolar (manic features) or psychotic disorders that occurred under tumor necrosis factor alpha (TNF-α) inhibitors therapy. Methods We searched the French pharmocovigilance database for reports of psychiatric ADR in the spectrum of bipolar (manic features) or psychotic disorders during treatment with TNF-α inhibitors. Psychiatric symptoms were divided in 2 categories: (i) confirmed diagnosis of manic episode or acute psychosis and (ii) psychiatric symptoms with psychotic or manic features but not meeting sufficient criteria for diagnosis of psychosis or manic disorder. Results Overall, 9942 reports of ADR were registered in the French pharmacovigilance database with TNF-α inhibitors, including 243 reports of psychiatric ADR. Among them, we identified 41 reports of psychotic or manic disorders as define above: 9 characterised manic episodes and 32 psychiatric disorders with psychotic or manic features. TNF-α inhibitors were the only medication suspected in 23 reports (56%). The delay between starting TNF-α inhibitors treatment and onset of symptoms varied from hours to years with a median time of 40 days. Psychiatric symptoms improved in 22/23 patients in whom the TNF-α inhibitor was withdrawn. Conclusion Depressive disorders are well-known ADR of TNF-α inhibitors, but we report, here, 41 reports of psychiatric ADR diagnosed as manic or psychotic disorders or in the spectrum of bipolar or psychotic disorders with these treatments. Epidemiological studies are needed to confirm this signal.