Avicenna Journal of Pharmaceutical Research

en Effect of Complementary Pharmacological Therapy on Fatigue in Patients with Multiple Sclerosis: A Systematic Review and Meta-Analysis تخصصي Special كاربردي Applicable Background: Fatigue is among the most common and disabling symptoms of multiple sclerosis (MS), significantly impairing quality of life, daily functioning, and work capacity. Given the variety of pharmacological approaches and the lack of consensus on their effectiveness, this study systematically evaluated the evidence on complementary pharmacological therapies for MS-related fatigue. Methods: A systematic search of PubMed, Scopus, and Web of Science (through May 2026) identified randomized controlled trials (RCTs) evaluating complementary pharmacological interventions for MS-related fatigue. Two reviewers independently performed study selection, data extraction, and risk-of-bias assessment using the Cochrane RoB 2 tool. Heterogeneity was assessed via chi-square and I² statistics, and publication bias via Begg’s and Egger’s tests. Pooled effects were reported as standardized mean differences (SMD) with 95% confidence intervals using a random-effects model. Results: Thirteen RCTs met inclusion criteria for the systematic review, with eight trials (439 participants) contributing to the quantitative synthesis. Complementary interventions significantly reduced fatigue compared with controls (SMD = -1.44, 95% CI: -2.30 to -0.58, p = 0.001), although heterogeneity was very high (I² = 93.7%). After excluding one outlying study, sensitivity analysis remained statistically significant while substantially lowering heterogeneity (SMD = -0.61, 95% CI: -0.91 to -0.31, p < 0.001; I² = 49.9%). No clear publication bias was detected (Begg’s p = 0.293; Egger’s p = 0.477; trim-and-fill method). Risk-of-bias analysis showed low risk for randomization and blinding across studies, though incomplete outcome data and unclear allocation concealment were common limitations. Conclusion: Complementary pharmacological therapy may reduce fatigue in some patients with MS, but current evidence remains insufficient to support a definitive, generalizable recommendation. Larger, methodologically standardized trials with consistent outcome reporting are needed to establish the conclusive effectiveness of these therapies.   Complementary Therapies, Fatigue, Meta-Analysis, Multiple Sclerosis, Randomized Controlled Trial, Systematic Review 106 115 http://ajpr.umsha.ac.ir/browse.php?a_code=A-10-2-91&slc_lang=en&sid=1 Meysam Hesari No Department of Clinical Pharmacy, Faculty of Pharmacy, Hamadan University of Medical Sciences, Hamadan, Iran Nasibeh Ghalandari n.ghalandari@umsha.ac.ir Yes Department of Clinical Pharmacy, Faculty of Pharmacy, Hamadan University of Medical Sciences, Hamadan, Iran Salman Khazaei No Department of Epidemiology, School of Health, Hamadan University of Medical Sciences, Hamadan, Iran