Bipolar disorder in people with multiple sclerosis: an updated systematic review and meta-analysis

BACKGROUND: Multiple Sclerosis (MS) is an autoimmune disorder characterized by inflammatory demyelination within the central nervous system. It is the second cause of severe disability and poor quality of life (QoL) in young adults. Previous studies have reported wide variation in the prevalence and risk of bipolar disorder (BD) among people with MS (PwMS), highlighting the need for a comprehensive analysis to obtain reliable estimates. This review proposed to investigate the overall prevalence of BD in PwMS and the relationship between BD and MS. METHODS: We conducted a systematic search of PubMed, Scopus, Web of Science, and Embase for all relevant articles published before January 1, 2025. The meta-analysis was conducted on three different effect sizes: prevalence, odds ratio, and hazard ratio, with their 95% confidence interval (CI). All statistical analyses were done utilizing R software, version 4.4.0, using the “meta” package. RESULTS: Out of the 3059 studies, 41 involving a total of 219,886 PwMS (71.7% female) and 7,523,553 healthy controls (HCs) (50.4% female), were included. The overall prevalence of BD in PwMS was 3.2% (95% CI: 1.8% to 4.6%, I2 = 97%, p-heterogeneity < 0.01). The pooled hazard ratio of developing BD in PwMS was 2.5 (95% CI: 1.2 to 5.3, p-value = 0.02, I2 = 99%), and its pooled odds ratio was 1.5 (95% CI: 1.1 to 2, p-value < 0.01, I2 = 40%). CONCLUSION: This study found that the overall prevalence of BD in PwMS was 3.2%, and PwMS have a significantly increased risk of developing BD. This result highlights the importance of regular follow-up and routine psychiatric screening in PwMS for timely diagnosis and management of BD in PwMS. CLINICAL TRIAL NUMBER: Not applicable.