Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2015 Mar;21(3):305-17.
doi: 10.1177/1352458514564487. Epub 2015 Jan 12.

The Incidence and Prevalence of Psychiatric Disorders in Multiple Sclerosis: A Systematic Review

Free PMC article

The Incidence and Prevalence of Psychiatric Disorders in Multiple Sclerosis: A Systematic Review

Ruth Ann Marrie et al. Mult Scler. .
Free PMC article


Background: Psychiatric comorbidity is associated with lower quality of life, more fatigue, and reduced adherence to disease-modifying therapy in multiple sclerosis (MS).

Objectives: The objectives of this review are to estimate the incidence and prevalence of selected comorbid psychiatric disorders in MS and evaluate the quality of included studies.

Methods: We searched the PubMed, PsychInfo, SCOPUS, and Web of Knowledge databases and reference lists of retrieved articles. Abstracts were screened for relevance by two independent reviewers, followed by full-text review. Data were abstracted by one reviewer, and verified by a second reviewer. Study quality was evaluated using a standardized tool. For population-based studies we assessed heterogeneity quantitatively using the I² statistic, and conducted meta-analyses.

Results: We included 118 studies in this review. Among population-based studies, the prevalence of anxiety was 21.9% (95% CI: 8.76%-35.0%), while it was 14.8% for alcohol abuse, 5.83% for bipolar disorder, 23.7% (95% CI: 17.4%-30.0%) for depression, 2.5% for substance abuse, and 4.3% (95% CI: 0%-10.3%) for psychosis.

Conclusion: This review confirms that psychiatric comorbidity, particularly depression and anxiety, is common in MS. However, the incidence of psychiatric comorbidity remains understudied. Future comparisons across studies would be enhanced by developing a consistent approach to measuring psychiatric comorbidity, and reporting of age-, sex-, and ethnicity-specific estimates.

Keywords: Multiple sclerosis; anxiety; bipolar disorder; comorbidity; depression; incidence; prevalence; psychosis; systematic review.

Conflict of interest statement

Conflicts of interest: Ruth Ann Marrie receives research funding from: Canadian Institutes of Health Research, Public Health Agency of Canada, Manitoba Health Research Council, Health Sciences Centre Foundation, Multiple Sclerosis Society of Canada, Multiple Sclerosis Scientific Foundation, Rx & D Health Research Foundation, and has conducted clinical trials funded by Sanofi-Aventis.

Nadia Reider has nothing to declare.

Olaf Stuve is an associate editor of JAMA Neurology, and he serves on the editorial boards of the Multiple Sclerosis Journal, Clinical and Experimental Immunology, and Therapeutic Advances in Neurological Disorders. He has participated in data and safety monitoring committees for Pfizer and Sanofi. Dr Stuve has received grant support from Teva Pharmaceuticals.

Jeffrey Cohen reports personal compensation for consulting from EMD Serono, Genentech, Genzyme, Innate Immunotherapeutics, Novartis, and Vaccinex. He receives research support paid to his institution from Biogen Idec, Consortium of MS Centers, US Department of Defense, Genzyme, US National Institutes of Health, National MS Society, Novartis, Receptos, Synthon, Teva, and Vaccinex.

Per Soelberg Sørensen has received personal compensation for serving on scientific advisory boards, steering committees, independent data monitoring boards in clinical trials, or speaking at scientific meetings from Biogen Idec, Merck Serono, Novartis, Genmab, TEVA, GSK, Genzyme, Bayer Schering, Sanofi-aventis and MedDay Pharmaceuticals. His research unit has received research support from Biogen Idec, Merck Serono, Teva, Sanofi-Aventis, Novartis, RoFAR, Roche, and Genzyme.

Maria Trojano has served on scientific Advisory Boards for Biogen Idec, Novartis and Merck Serono; has received speaker honoraria from Biogen-Idec, Sanofi-Aventis, Merck-Serono, Teva and Novartis; has received research grants from Biogen-Idec, Merck-Serono, and Novartis.

Gary Cutter has served on scientific advisory boards for and/or received funding for travel from Innate immunity, Klein-Buendel Incorporated, Genzyme, Medimmune, Novartis, Nuron Biotech, Spiniflex Pharmaceuticals, Somahlution, Teva Pharmaceuticals; receives royalties from publishing Evaluation of Health Promotion and Disease Prevention (The McGraw Hill Companies, 1984); has received honoraria from GlaxoSmithKline, Novartis, Advanced Health Media Inc, Biogen Idec, EMD Serono Inc, EDJ Associates Inc, the National Heart, Lung, and Blood Institute, National Institute of Neurological Diseases and Stroke, National Marrow Donor Program, Consortium of Multiple Sclerosis Centers; Mt. Sinai School of Medicine, and Teva Pharmaceuticals; and has served on independent data and safety monitoring committees for Apotek, Ascendis, Biogen-Idec, Cleveland Clinic, Glaxo Smith Klein Pharmaceuticals, Gilead Pharmaceuticals, Modigenetech/Prolor, Merck/Ono Pharmaceuticals, Merck, Neuren, PCT Bio, Teva, Vivus, NHLBI (Protocol Review Committee), NINDS, NMSS, and NICHD (OPRU oversight committee).

Stephen Reingold reports personal consulting fees from the National Multiple Sclerosis Society (NMSS) and the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS), during the conduct of this work; and over the past three years, personal consulting fees from Bayer HealthCare, Biogen Idec, Coronado Biosciences Inc, the Cleveland Clinic Foundation, Eli Lilly & Company, from EMD Serono and Merck Serono, Genentech, F. Hoffmann-LaRoche, Ironwood Pharmaceuticals Inc, ISIS Pharmaceuticals Inc, Medimmune Inc, Novartis Pharmaceuticals Corporation, Observatoire Français de la Sclérosis en Plaques, Opexa Therapeutics, Sanofi-Aventis, SK Biopharmaceuticals, Synthon Pharmaceuticals Inc, Teva Pharmaceutical Industries, and Fondation pour l’aide à la Recherche sur la Sclérosis en Plaques, for activities outside of the submitted work.


Figure 1.
Figure 1.
Forest plot of the prevalence of anxiety in multiple sclerosis in population-based studies.
Figure 2.
Figure 2.
Forest plot of the prevalence of depression in multiple sclerosis in population-based studies.
Figure 3.
Figure 3.
Forest plot of the prevalence of depression in multiple sclerosis in population-based studies.

Similar articles

See all similar articles

Cited by 61 articles

See all "Cited by" articles


    1. Marrie RA, Horwitz R, Cutter G, et al. Cumulative impact of comorbidity on quality of life in MS. Acta Neurol Scand 2012; 125: 180–186. - PMC - PubMed
    1. Mohr DC, Goodkin DE, Likosky W, et al. Treatment of depression improves adherence to interferon beta-1b therapy for multiple sclerosis. Arch Neurol 1997; 54: 531–533. - PubMed
    1. Marrie RA, Fisk JD, Yu BN, et al. Mental comorbidity and multiple sclerosis: Validating administrative data to support population-based surveillance. BMC Neurol 2013; 13: 16. - PMC - PubMed
    1. Rodgers J, Bland R. Psychiatric manifestations of multiple sclerosis: A review. Can J Psychiatry 1996; 41: 441–445. - PubMed
    1. Patten SB, Svenson LW, Metz LM. Psychotic disorders in MS: Population-based evidence of an association. Neurology 2005; 65: 1123–1125. - PubMed