In this study we aimed to estimate the effectiveness of pharmacological, nutraceutical, and phytopharmaceutical treatments on CRF. Methods: Ovid MEDLINE, Ovid Embase, Ovid Psych info, CINHAHL and Cochrane Library databases were searched up to 30 September 2021. Randomized controlled trials of pharmacological, nutraceutical and phytopharmaceutical interventions for treatment of CRF for at least one week duration and have used valid tool to assess severity of CRF as a primary or secondary outcome were considered. Results: 32 eligible studies (4896 patients) were reviewed. For the overall meta-analysis, the random effect models yielded the treatment effect
(95% CI) of 􀀀0.29 (-0.48,-0.09), p < 0.001. The meta-analysis did not show significant reduction of CRF with treatment with ginseng (n = 6), guarana (n = 3), megestrol (n = 2), mistletoe (n = 3), psychostimulants (n = 14), SSRI/antidepressants (n = 2). Corticosteroids (n = 2) showed significant reduction in CRF with treatment effects of 0.94 (-1.21, -0.67), p <0.0001, respectively. Conclusions: In this study, overall meta-analysis of all studies demonstrates significant reduction of CRF using
Pharmacological, Nutraceutical and Phytopharmaceutical interventions with a pooled standardized
treatment effect of -0.29. Metanalysis of Corticosteroids studies showed significant reduction in CRF.
Further studies are needed.