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Development of further effective and well-tolerated disease-modifying therapies (DMTs) for multiple sclerosis (MS) is a major research priority. Strategies include ‘repurposing’ drugs, which are already approved for other indications, as DMTs. While selective serotonin reuptake inhibitors (SSRIs) are widely used as antidepressants, preclinical and clinical studies suggest that disease-modifying effects in relapsing and progressive MS are plausible1 (see online additional material). Furthermore, a recent Cochrane systematic review demonstrated that, in adults with stroke, SSRIs improved measures of dependence, disability and neurological impairment.2 We therefore aimed to identify, assess and synthesise randomised controlled trials (RCTs) examining effects of SSRIs on the MS disease course.
Methodology and reporting follows Cochrane Collaboration and PRISMA recommendations.2 We searched The Cochrane Library, MEDLINE, EMBASE, PsychINFO, CINAHL and BIOSIS (20 March 2013) (see online material for full-search strategies). We performed a cited reference search, scrutinised reference lists and contacted study authors.
We included RCTs only of SSRIs compared with placebo or usual care in subjects with definite MS. Our primary outcome was MS disease activity (including direct or surrogate clinical or other measures of disease activity or progression). Secondary outcomes were depressive or other symptoms, quality of life and adverse events. Two authors independently extracted methodological and study data. We assessed risk of bias using Cochrane Collaboration recommendations.2 Where appropriate, we calculated event rates and event rate …