Pharmacologic Interventions for Fatigue in Cancer and Transplantation: A Meta-Analysis

Background: Our objective was to determine whether, compared with control interventions, pharmacologic interventions reduce the severity of fatigue in patients with cancer or recipients of hematopoietic stem-cell transplantation (HSCT). Methods: For a systematic review, we searched medline, embase, the Cochrane Central Register of Controlled Trials, CINAHL, and PsychINFO for randomized trials of systemic pharmacologic interventions for the management of fatigue in patients with cancer or recipients of HSCT. Two authors independently identified studies and abstracted data. Methodologic quality was assessed using the Cochrane Risk of Bias tool. The primary outcome was fatigue severity measured using various fatigue scales. Data were synthesized using random-effects models. Results: In the 117 included trials (19,819 patients), the pharmacologic agents used were erythropoietins (n = 31), stimulants (n = 19), L-carnitine (n = 6), corticosteroids (n = 5), antidepressants (n = 5), appetite stimulants (n = 3), and other agents (n = 48). Fatigue was significantly reduced with erythropoietin [standardized mean difference (SMD): −0.52; 95% confidence interval (ci): −0.89 to −0.14] and with methylphenidate (SMD: −0.36; 95% CI: −0.56 to −0.15); modafinil (or armodafinil) and corticosteroids were not effective. Conclusions: Erythropoietin and methylphenidate significantly reduced fatigue severity in patients with cancer and in recipients of HSCT. Concerns about the safety of those agents might limit their usefulness. Future research should identify effective interventions for fatigue that have minimal adverse effects.