Reviewed: Kashani L, Eslatmanesh S, Saedi N, et al. Comparison of saffron versus fluoxetine in treatment of mild to moderate postpartum depression: a double-blind, randomized clinical trial. Pharmacopsychiatry. 2017;50(2):64-68.

An estimated 10-15% of new mothers suffer from postpartum depression. Treatment with selective serotonin reuptake inhibitors (SSRIs), such as fluoxetine, is the first-line therapy, but remission rates with these treatments are low, and SSRIs can have significant adverse effects. The dried stigma of saffron (Crocus sativus, ridaceae) flowers has been reported to improve depression and premenstrual symptoms. The purpose of this randomized, double-blind, controlled study was to compare the efficacy of saffron with fluoxetine in the treatment of mild-to-moderate postpartum depression. There was no placebo comparison group, so the absolute antidepressant effect of either treatment could not be determined.

Patients (N = 68, 18-45 years old) with mild-to-moderate postpartum depression according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) criteria were enrolled. The study was conducted between September and December 2015 at the outpatient clinics of Yas Women General Hospital, Arash Hospital, and Baharloo Hospital, which are all affiliated with Tehran University of Medical Sciences and located in Tehran, Iran. Included patients were four to 12 weeks post-childbirth and had scores of 10-18 on the 17-item Hamilton Depression Rating Scale (HDRS). Excluded patients were lactating or had psychotic depression, a history of suicidal or infanticidal thoughts, a history of bipolar disorder, substance or alcohol dependence, hypothyroidism, acute medical illness, or any diagnosis other than postpartum depression on axis 1 of the DSM-IV-TR. 

Patients received either 15 mg of saffron stigma extract (SaffroMood; IMPIRAN Co.; Tehran, Iran; reported to contain 1.65-1.75 mg of crocin per capsule) twice daily or 20 mg of fluoxetine (Abidi; Tehran, Iran) twice daily for six weeks. Other psychotropic drugs or behavior therapy were not permitted. Depressive symptoms were assessed with the HDRS at baseline and weeks one, three, and six. A “partial responder” was defined as having a 25-50% reduction in the HDRS score; a “responder” was defined as having at least a 50% reduction in HDRS score; and a “remitter” was defined as having an HDRS score of seven or less. 

Baseline characteristics were similar between groups. Two patients from each group were discontinued from the analysis because they developed severe depression. 

At study end, 18.8% of the saffron group and 21.9% of the fluoxetine group were remitters; there was no significant difference between the two groups. A total of 40.6% of the saffron group and 50% of the fluoxetine group were responders; there was no significant difference between the groups. All patients had at least a partial response, and there was no significant difference between the two groups in HDRS score reduction from baseline. Patients in the fluoxetine group had a greater frequency of headache, dry mouth, daytime drowsiness, constipation, and sweating, but there was no significant difference between groups in the incidence of these adverse effects.

The authors speculate that saffron may be as effective as fluoxetine in improving symptoms of postpartum depression. They also conclude that saffron is safe in this population. Limitations of the study are its short duration, lack of long-term follow-up, relatively small population size, use of a single measure of depression severity, and lack of placebo group. These findings should be confirmed in a more robust study to address these limitations. Nonetheless, saffron may be a promising treatment option for women with postpartum depression. 

—Heather S. Oliff, PhD