Depressive disorders are very common in clinical practice, with approximately 11.3 of all adults afflicted during any one year. The introduction of atypical antidepressants, such as bupropion, nefazadone, and mirtazapine, has added substantially to the available pharmacopoeia for depression. Nonetheless, rates of remission tend to be low and the risk of relapse and recurrence remains high (Demyttenaere, 1997). 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 disorder, difficult labor, 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 compare the efficacy of Crocus sativus with imipramine in the treatment of mild to moderate depression in a 6-week double blind, randomised 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. Patients have 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 capsule of saffron 30 mg/day (TDS) (Group 1) and capsule of imipramine 100 mg/day (TDS) (Group 2) for a 6-week study.The outcome of the two groups was assessed using Hamilton Depression Rating Scale. All patient completed the trial. Patients were assessed by a third year resident of psychiatry at baseline and after 1, 2, 3, 4 and 6 weeks after the medication started. The principal measure of the outcome 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 six 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 were 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 (d.f. = 28, P = 0.43). Saffron at this dose was found to be effective similar to imipramine in the treatment of mild to moderate depression (F = 2.91, d.f. = 1, P = 0.09) . In addition, the difference between the two protocols was not significant at week 6 (d.f. =28, P= 0.33). In the imipramine group anticholinergic effects such as dry mouth and also sedation were observed more often that was predictable.

The main overall finding from this study is that saffron may be of therapeutic benefit in the management of mild to moderate depression. To the best of our knowledge this is the first clinical trial that supports this indication for saffron. A large- scale trial is justified.

Demyttenaere K. (1997). J. Affective Disorders 43, 27-39