Comparing the effectiveness, safety and tolerability of interventions for depressive symptoms in people with multiple sclerosis: A systematic review

Background: Depression is more common in people with multiple sclerosis (MS) compared to the general population. While many interventions are available for treating depressive symptoms in people with MS, it is unclear how different intervention modalities compare. This systematic review aimed to compare the reported effectiveness, safety, and tolerability of interventions for treating depressive symptoms in people with MS. Methods: We systematically searched 7 databases for randomised controlled trials (RCTs) of pharmaceutical, psychological, physical, and electromagnetic stimulation interventions which aimed to reduce depressive symptoms amongst adults with MS. Screening, data extraction and risk of bias assessment were completed by at least two independent researchers. We planned to synthesise the data using network meta-analysis, however the high risk of bias of the included trials resulted in synthesis without meta-analysis. Results: Of 1,949 citations, 31 trials (21 psychological, seven physical activity, two pharmaceutical, and one combination) were included, comprising 2,289 participants. Of the 31 eligible trials 24 were at high and six at moderate risk of bias, which precluded meta-analysis. Twenty-six trials reported on efficacy and only 16/31 reported safety and/or tolerability, using inconsistent methods. Conclusions: The current strength of the evidence for treating depressive symptoms in MS is low, therefore, we are not able to summarise or make comparisons between the treatment modalities. There is an urgent need for high-quality and diverse trials investigating treatment options for depression in people with MS. This can only be achieved if the conduct and reporting of RCTs are improved.