The efficacy of Crocus sativus (Saffron) versus placebo and Fluoxetine in treating depression: a systematic review and meta-analysis

Mojtaba Khaksarian,1,2 Masoud Behzadifar,1 Meysam Behzadifar,3,4 Maryam Alipour,5 Firouzeh Jahanpanah,3 Tania Simona Re,6–8 Fabio Firenzuoli,6 Riccardo Zerbetto,7 Nicola Luigi Bragazzi7–101Razi Herbal Medicines Research Center, Lorestan University of Medical Sciences, Khorramabad, Iran; 2Department of Physiology, School of Medicine, Lorestan University of Medical Sciences, Khorramabad, Iran; 3Social Determinants of Health Research Center, Lorestan University of Medical Sciences, Khorramabad, Iran; 4Department of Epidemiology, Faculty of Health and Nutrition, Lorestan University of Medical Sciences, Khorramabad, Iran; 5Faculty of Biological Science & Technology, Shahid Beheshti University of Medical Sciences, Tehran, Iran; 6Department of Experimental and Clinical Medicine, Center for Integrative Medicine, Careggi University Hospital, University of Florence, Florence, Italy; 7Centro Studi Terapia della Gestalt (CSTG), Milan, Italy; 8UNESCO Chair “Health Anthropology Biosphere and Healing Systems”, University of Genoa, Genoa, Italy; 9Postgraduate School of Public Health, Department of Health Sciences (DISSAL), University of Genoa, Genoa, Italy; 10Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, and Maternal/Child Sciences (DINOGMI), University of Genoa, Genoa, ItalyBackground: Depression represents a serious public health concern, imposing a high burden, both in epidemiological and clinical terms. Crocus sativus (Saffron) is a herbal remedy that has anti-cancer, anti-oxidant, anti-inflammatory and anti-platelet properties. However, the exact mechanisms of Saffron in treating depression are not yet clear. This study was conducted to evaluate the effectiveness of Saffron versus placebo and Fluoxetine in the treatment of depressed patients.Methods: Different bibliographic thesauri, namely the Cochrane Library, Scopus, PubMed/MEDLINE, Centre for Reviews and Dissemination (CRD), EMBASE, and ISI/Web of Science (WoS) were searched up to May 2018. Effect sizes were computed as Standardized Mean Differences (SMD) with their 95% confidence interval (CI). To evaluate the heterogeneity among the studies, I2, test was carried out.Results: Eight studies were included. The SMD was −0.86 (95% CI: −1.73 to 0.00) concerning the comparison of Saffron with placebo. The SMD was found to be 0.11 (95% CI: −0.20 to 0.43) concerning the comparison of Saffron with Fluoxetine. In both sensitivity analyses, the results did not statistically change, confirming the stability of the findings.Conclusion: The findings of this study showed that Saffron administration was well comparable with Fluoxetine and placebo.Keywords: systematic review, meta-analysis, Saffron, Fluoxetine, depressio