Exploring the association between monoclonal antibodies and depression and suicidal ideation and behaviour: A VigiBase study

Background: Recently exposure to monoclonal antibodies has been associated with rare adverse neuropsychiatric effects, eg, depression, suicidal ideation, and behavior. Understanding these associations is difficult given the diversity of indications for use of these products. So far, also little is known about any differential risk between individual monoclonal antibodies. Objectives: To quantify and characterize spontaneously reported adverse drug reactions (ADRs) related to depression and suicidal ideation and behavior for monoclonal antibodies. Methods: ADRs reported until December 2017 in VigiBase, the WHO global database of Individual Case Safety Reports, were included. A MedDRA standardized search was used to identify reports related to depression and suicidal ideation and behaviour for monoclonal antibodies, as well as for all other drugs in the database. Monoclonal antibodies that had been authorised by any global regulatory authority (eg, FDA and EMA) for at least 3 years were included. Reporting odds ratios were estimated and compared relative with bevacizumab as a reference. Results: A total of 44 monoclonal antibodies were included in the study. For these, 9455 reports related to depression and 1770 reports related to suicidal ideation and behaviour were analysed. For both depression and suicidal ideation and behaviour, natalizumab and belimumab showed the highest relative (to bevacizumab) reporting odds ratio, ie, 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. These two products show little to no mechanistic commonalities. Moreover, we found several compounds with mechanistic commonalities with comparable reporting odds ratios (TNF-alpha inhibitors, alpha-4 integrin antibodies, checkpointinhibitors, and HER-2 antibodies). Conclusions: Adverse neuropsychiatric effects are seen in patients exposed to monoclonal antibodies. Two antibodies peaked (ie, natalizumab and belimumab) regarding reporting of depression and suicidal ideation and behaviour. For the interpretation of these data, the indications for use and other population characteristics need further consideration.