title: Saffron (Crocus sativus L.) and major depressive disorder: a meta-analysis of randomized clinical trials.
abstract: BACKGROUND
  Due to safety concerns and side effects of many antidepressant medications, herbal psychopharmacology research has increased, and herbal remedies are becoming increasingly popular as alternatives to prescribed medications for the treatment of major depressive disorder (MDD). Of these, accumulating trials reveal positive effects of the spice saffron (Crocus sativus L.) for the treatment of depression. A comprehensive and statistical review of the clinical trials examining the effects of saffron for treatment of MDD is warranted.
  
  
  OBJECTIVE
  The purpose of this study was to conduct a meta-analysis of published randomized controlled trials examining the effects of saffron supplementation on symptoms of depression among participants with MDD.
  
  
  METHODS
  We conducted electronic and non-electronic searches to identify all relevant randomized, double-blind controlled trials. Reference lists of all retrieved articles were searched for relevant studies.
  
  
  METHODS
  The criteria for study selection included the following: (1) adults (aged 18 and older) with symptoms of depression, (2) randomized controlled trial, (3) effects of saffron supplementation on depressive symptoms examined, and (4) study had either a placebo control or antidepressant comparison group.
  
  
  METHODS
  Using random effects modeling procedures, we calculated weighted mean effect sizes separately for the saffron supplementation vs placebo control groups, and for the saffron supplementation vs antidepressant groups. The methodological quality of all studies was assessed using the Jadad score. The computer software Comprehensive Meta-analysis 2 was used to analyze the data.
  
  
  RESULTS
  Based on our pre-specified criteria, five randomized controlled trials (n = 2 placebo controlled trials, n = 3 antidepressant controlled trials) were included in our review. A large effect size was found for saffron supplementation vs placebo control in treating depressive symptoms (M ES = 1.62, P < 0.001), revealing that saffron supplementation significantly reduced depression symptoms compared to the placebo control. A null effect size was evidenced between saffron supplementation and the antidepressant groups (M ES = -0.15) indicating that both treatments were similarly effective in reducing depression symptoms. The mean Jadad score was 5 indicating high quality of trials.
  
  
  CONCLUSIONS
  Findings from clinical trials conducted to date indicate that saffron supplementation can improve symptoms of depression in adults with MDD. Larger clinical trials, conducted by research teams outside of Iran, with long-term follow-ups are needed before firm conclusions can be made regarding saffron's efficacy and safety for treating depressive symptoms.
authors.affiliation: Department of Sport and Exercise Sciences, Jacksonville University, Jacksonville, Florida 32211, USA; E-mail: hhausen@ju.edu.
authors.forename: Heather Ann
authors.initials: HA
authors.lastname: Hausenblas
authors.forename: Debbie
authors.initials: D
authors.lastname: Saha
authors.forename: Pamela Jean
authors.initials: PJ
authors.lastname: Dubyak
authors.forename: Stephen Douglas
authors.initials: SD
authors.lastname: Anton
mesh_terms: D027622:Crocus / Q000009:adverse effects; D003865:Major Depressive Disorder / Q000188:drug therapy*; D006801:Humans; D008517:Phytotherapy; D016032:Randomized Controlled Trials as Topic