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Prevalence of bipolar disorder in multiple sclerosis: a systematic review and meta-analysis
  1. Boney Joseph1,2,
  2. Aiswarya L Nandakumar1,
  3. Ahmed T Ahmed2,3,
  4. Neethu Gopal4,
  5. M Hassan Murad5,6,
  6. Mark A Frye1,
  7. W Oliver Tobin2,7,
  8. Balwinder Singh1
  1. 1Department of Psychiatry and Psychology, Mayo Clinic, Rochester, Minnesota, USA
  2. 2Department of Neurology, Mayo Clinic, Rochester, Minnesota, USA
  3. 3Clinical and Translational Science Graduate Program, Mayo Clinic Graduate School of Biomedical Sciences, Rochester, Minnesota, USA
  4. 4Department of Neurology, Mayo Clinic, Jacksonville, Florida, USA
  5. 5Evidence-Based Practice Research Program, Mayo Clinic, Rochester, Minnesota, USA
  6. 6Division of Preventive, Occupational and Aerospace Medicine, Mayo Clinic, Rochester, Minnesota, USA
  7. 7Center for Multiple Sclerosis and Autoimmune Neurology, Mayo Clinic, Rochester, Minnesota, USA
  1. Correspondence to Dr Balwinder Singh, Department of Psychiatry and Psychology, Mayo Clinic, Rochester, MN 55905, USA; singh.balwinder{at}


Background Multiple sclerosis (MS) is a chronic disabling, demyelinating disease of the central nervous system and is often associated with psychiatric comorbidities. Some studies suggest increased prevalence of bipolar disorder (BD) in MS.

Objective To conduct a systematic review and meta-analysis assessing the prevalence of BD in adults with MS.

Methods We registered this review with PROSPERO and searched electronic databases (Ovid MEDLINE, Central, Embase, PsycINFO and Scopus) for eligible studies from earliest inception to October 2020. Prevalence data of BD in adult patients with MS were extracted. Meta-analysis was conducted using random-effects model.

Findings Of the 802 articles that were screened, 23 studies enrolling a total of 68 796 patients were included in the systematic review and meta-analysis. The pooled prevalence rate of BD in patients with MS was 2.95% (95% CI 2.12% to 4.09%) with higher prevalence in the Americas versus Europe. The lifetime prevalence of BD was 8.4% in patients with MS. Subgroup analysis showed a higher prevalence of BD in MS in females (7.03%) than in males (5.64%), which did not reach statistical significance (p=0.53).

Conclusions This meta-analysis suggests a high lifetime prevalence of BD in patients with MS. Patients with MS should be routinely screened for BD. Further assessment of bipolar comorbidity in MS through prospective studies may help in developing effective management strategies and may improve treatment outcomes in patients with MS.

  • depression & mood disorders
  • adult psychiatry

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  • Contributors All authors have contributed significantly to this manuscript and agree with its content. Study concept and design: BS, BJ and ALN. Acquisition of data: BS, BJ, ALN and NG. Analysis/interpretation of data: BS, BJ, ATA and MHM. Drafting of article: BJ, ALN, ATA, NG, MHM, MAF, WOT and BS. Revision of article: BJ, ALN, ATA, NG, MHM, MAF, WOT and BS.

  • Funding BS received research time support from Medibio (unrelated to the current study) and Mayo Clinic. WOT received research/grant support from Mallinckrodt Pharmaceuticals. MAF reports grant support from Assurex Health, Mayo Foundation, Medibio. Consultant (Mayo) - Actify Neurotherapies, Allergan, Intra-Cellular Therapies, Janssen, Myriad, Neuralstem, Takeda, Teva Pharmaceuticals. He reports CME/Travel/Honoraria from the American Physician Institute, CME Outfitters, Global Academy for Medical Education. Other authors have none to declare.

  • Competing interests None declared.

  • Patient consent for publication Not required.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement Data are available on reasonable request. The data that support the findings of this study are available from the corresponding author on reasonable request.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.

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