Depression is a serious disorder in today’s society with estimates of lifetime prevalence as high as 21% of the general population in some developed countries. As defined by the American Psychiatric Association, depression is a heterogeneous disorder often manifested with symptoms at the psychological, behavioural and physiological levels. Such patients are often reluctant to take synthetic antidepressants in their appropriate doses due to their anticipated side effects including inability to drive a car, dry mouth, constipation and sexual dysfunction [1]. Thus, there is a need for more effective and less toxic agents. Plants extracts are some of the most attractive sources of new drugs, and have been shown to produce promising results for the treatment of depression. In Asian medicine and in particular Persian traditional medicine, saffron is used to treat menstrual disorders, difficult labour, inflammation, vomiting, and throat diseases. Crocus sativus is also used to treat depression. Many medicinal plants textbooks refer to this usage whereas there is no evidence-based document. Our objective was to assess the efficacy of stigmas of Crocus sativus (saffron) in the treatment of mild to moderate depression in a 6-week double-blind, placebo controlled, randomized trial.

Thirty adult outpatients who met the Diagnostic and Statistical Manual of Mental Disorders, 4 th edition, for major depression based on the structured clinical interview for DSM IV participated in the trial. All participants provided written informed consent, and the protocol satisfied the Tehran University of Medical Sciences Ethics Committee requirements. Patients had a baseline Hamilton Rating Scale for Depression score of at least 18. In this double-blind, single-centre trial, patients were randomly assigned to receive a capsule of saffron 30 mg day^-1 (twice daily) (Group 1) and a capsule of placebo (twice daily) (Group 2) for a 6-week study.The outcome of the two groups was assessed using the Hamilton Depression Rating Scale (HAM-D). All patients completed the trial. Patients were assessed by a third year resident of psychiatry at baseline and 1, 2, 3, 4 and 6 weeks after the medication started. The principal outcome measure was the 17-item HAM-D. The rater used standardized instructions in the use of HAM-D. A two-way repeated measures analysis of variance (time- treatment interaction) was used. The two groups as a between-subjects factor (group) and the five measurements during treatment as the within-subjects factor (time) were considered. In addition, a one-way repeated measures analysis of variance with a two-tailed post hoc Tukey mean comparison test was performed in the change from baseline in each group. To compare the two groups at baseline and the outcome of two groups at the end of the trial, an unpaired Student's t-test with a two-sided P value was used. To compare the demographic data, Fisher’s exact test was performed.

There were no significant differences between the two groups at week 0 (baseline) on the HAM-D (t = 0.34, d.f. = 38, P = 0.73). At 6 weeks, Crocus sativus produced a significantly better outcome on the HAM-D than placebo (d.f. = 1, F = 18.89, P < 0.001). There were no significant differences in the two groups in terms of observed side effects. In addition, the difference between the two protocols was significant at week 6 (t = 6.81, d.f. = 38, P < 0.0001). There were no significant differences in the two groups in terms of observed side effects.

The results of this study indicate the efficacy of Crocus sativus in the treatment of mild to moderate depression. A large- scale trial is justified.