Effects of meeting exercise guidelines on depression and anxiety in multiple sclerosis – a systematic review and meta-analysis

Depression and anxiety are common in multiple sclerosis (MS), significantly affecting quality of life. Previous studies on exercise interventions for mental health in persons with MS (PwMS) have shown mixed results, partly due to inconsistent adherence to the Physical Activity Guidelines for Multiple Sclerosis (PAG-MS). This study aimed to evaluate the effects of PAG-MS-compliant exercise on depression and anxiety outcomes in PwMS. A systematic search was performed in EMBASE, PsycINFO, Web of Science, SPORTDiscuss, PubMed, Scopus, and CINAHL through October 2024 to identify randomized controlled trials (RCTs). Eligible studies involved adults with MS and focused on exercise regimens compliant with PAG-MS. Comparisons were made with non-PAG-MS exercise regimens or no exercise at all. Two independent reviewers screened studies, extracted data, and assessed the risk of bias. Depression and anxiety outcomes were analyzed using meta-analyses, incorporating minimal clinically important difference (MCID) thresholds to determine clinical significance. Twelve RCTs involving 458 participants we included. Depression outcomes showed significant improvement (MD: −4.46 [95% CI: −6.90, −2.01], P ˂ 0.01), exceeding the MCID threshold of 3.00 points on the Beck Depression Inventory scale. Anxiety outcomes, analyzed from two RCTs, showed non-significant improvement (SMD: −0.87 [95% CI: −2.46, 0.72], <i>p</i> = .29). Overall, 58.33% of studies had a high risk of bias. Interventions that meet PAG-MS demonstrate clinically meaningful improvements in depression, supporting their use as a non-pharmacological treatment strategy. However, given the limited data on anxiety outcomes, further research is needed to clarify the potential benefits in this domain.