Effects of exercise and pharmacotherapy on fatigue in stroke patients: A systematic review with meta-analysis

• The impact of post-stroke fatigue (PSF) on the functional recovery of patients with stroke is significant. • PSF is closely linked to mortality and prognosis and indirectly affects psychological well-being and quality of life. • Our review suggests that both exercise and pharmacotherapy may be effective in reducing the PSF. • However, the limitations of these trials, such as small sample sizes and potential bias, highlight the necessity for larger sample sizes and appropriate treatment durations in future research. This systematic review and meta-analysis aimed to investigate the efficacy of exercise and pharmacological interventions in mitigating fatigue in acute, subacute, and chronic phases of stroke recovery. PubMed, Embase, Science Direct, Web of Science, Scopus, and Google Scholar databases were searched for articles published before December 2023. Randomized controlled trials that assessed the effectiveness of exercise and pharmacotherapy on PSF in patients with acute, subacute, and chronic strokes were included. Studies that met the following criteria were included: participants who had experienced PSF, were older than 18 years, and used exercise or pharmacotherapy as interventions. The I2 test and funnel plot were used to examine heterogeneity and publication bias. The quality of the studies was assessed using the Critical Appraisal Checklist for Studies created by the Joanna Briggs Institute. Twelve publications were selected from 1,472 citations for the final qualitative analysis. The articles were published between 2007 and 2023, with 686 participants, ranging from 06 to 119. Physical exercise and pharmacological treatments (fluoxetine, modafinil, and (−)-OSU6162) were associated with decreased fatigue severity at the end of treatment (pooled mean difference = −2.90, 95 % CI: −6.83 to 1.02). However, these trials were small and had a significant risk of bias. Our findings suggest that exercise and pharmacotherapy may reduce PSF. However, the small sample size and potential bias of the trials underscores the need for larger sample sizes and appropriate treatment durations.