Exploring the association between monoclonal antibodies and depression and suicidal ideation and behavior: A vigibase study

Background/Introduction: Recently, exposure to monoclonal antibodies has been associated with neuropsychiatric effects, e.g., depression, and suicidal ideation and behavior. So far, little is known about any differential risk between individual monoclonal antibodies and the potential underlying mechanism. Objective/Aim: To quantify and characterize spontaneously reported adverse drug reactions (ADRs) of monoclonal antibodies related to depression and suicidal ideation and behavior. Furthermore, to explore the association between the mechanism of action of the monoclonal antibodies and these ADRs. Methods: ADRs reported until December 2017 in VigiBase, the WHO global database of Individual Case Safety Reports, were included. Reports related to depression and suicidal ideation and behaviour (MedDRA standardized search) for monoclonal antibodies were extracted. Monoclonal antibodies that had been authorised by any global regulatory authority (e.g. FDA, EMA) for at least 3 years were included. Associations were tested by estimating reporting odds ratios (RORs) for the monoclonal antibodies separately (using bevacizumab as a reference) as well as grouped on their influence on the immune system (not influencing the immune system (reference), suppressing the immune system, and stimulating the immune system). Monoclonal antibodies suppressing the immune system were further stratified according to their intended indication (autoimmune diseases, cancer). Results: A total of 44 monoclonal antibodies were included for which a total of 2924,319 adverse drug reactions were reported. For these 44 monoclonal antibodies, 9455 (0.3%) reports related to depression and 1770 (0.1%) reports related to suicidal ideation and behaviour were analysed. For both depression and suicidal ideation and behaviour, natalizumab and belimumab showed the highest ROR relative to bevacizumab, i.e. for depression 5.7 (95% CI 5.0-6.4) and 5.1 (95% CI 4.2-6.2), for suicidal ideation and behaviour 12.0 (95% CI 7.9-18.3) and 20.2 (95% CI 12.4-33.0) respectively. Monoclonal antibodies suppressing the immune system showed higher ROR relative to monoclonal antibodies not influencing the immune system, i.e. for depression 1.9 (95% CI 1.8-2.0) and for suicidal ideation and behaviour 3.6 (95% CI 3.0-4.4). This difference was only seen in the monoclonal antibodies suppressing the immune system that are used for treating autoimmune diseases. Conclusion: Adverse neuropsychiatric effects are seen in patients exposed to monoclonal antibodies. Two antibodies peaked relative to bevacizumab (i.e. natalizumab, belimumab) regarding reporting of depression and suicidal ideation and behaviour. Furthermore, monoclonal antibodies used for treating autoimmune diseases showed higher RORs compared to monoclonal antibodies not influencing the immune system. For the interpretation of these data the indications for use and other population characteristics need further consideration.