A systematic review of systematic reviews and pooled meta-analysis on pharmacological interventions to improve cancer-related fatigue

Background: Evidence regarding the pharmacological interventions to manage cancer-related fatigue (CRF) is currently synthesized in several systematic reviews, portraying a fragmented literature synthesis. Thus, we aimed to critically appraise the available systematic reviews on pharmacological intervention for improving CRF in adult cancer patients. Methods: Three databases were systematically searched from January 2010 to July 2020. The pooled meta-analyses’ effect sizes (standardized mean difference, SMD) were quantitatively pooled using a random-effects model. Chi-squared (Q) and I-square statistics (I²) tested the heterogeneity. Results: The SMD of the effect of psychostimulants on CRF was −0.20 (95 % CI: −0.32, 0.08; p < 0.0001), along with significant higher improvement of fatigue (SMD=-0.69; 95 % CI=-1.29, -0,09, p < 0.0001) after methylphenidate administration. No statistical differences were found in the occurrences of adverse events between methylphenidate and placebo. Conclusions: This study corroborated that psychostimulant therapy may be moderately effective in reducing CRF. Scarce evidence on the short- and long-term adverse events. PROSPERO: CRD42020181879 (registration date: 26/07/2020).