Background: Objective was to determine whether pharmacological interventions reduce the severity of fatigue in patients with cancer or hematopoietic stem cell transplant (HSCT) recipients as compared to control interventions.

Methods: We conducted a systematic review and searched MEDLINE, Embase, Cochrane Central Register of Controlled Trials, CINAHL and PsychINFO for randomized trials of systemic pharmacological interventions for the management of fatigue in patients with cancer or HSCT recipients. Two authors independently identified studies and abstracted data. Methodological quality was assessed using the Cochrane Risk of Bias tool. Primary outcome was fatigue severity across different fatigue scales. Data were synthesized with random effects models.

Results: There were 117 trials (19,819 patients) included. Pharmacological agents were: erythropoietins (n=31); stimulants (n=19); L-carnitine (n=6); corticosteroids (n=5); anti-depressants (n=5), appetite-stimulants (n=3) and other agents (n=48). Erythropoietin (standardized mean difference (SMD) -0.52, 95% confidence interval (CI) -0.89 to -0.14) and methylphenidate (SMD -0.36, 95% CI -0.56 to -0.15) significantly reduced fatigue while modafinil/armodafinil and corticosteroids were not effective.

Conclusions: Erythropoietin and methylphenidate significantly reduced fatigue severity in patients with cancer and in HSCT recipients. Concerns regarding the safety of these agents may limit their usefulness. Future research should identify effective interventions for fatigue with minimal adverse effects.