Reviewed: Shahmansouri N, Farokhnia M, Abbasi S-H, et al. A randomized, double-blind, clinical trial comparing the efficacy and safety of Crocus sativus L. with fluoxetine for improving mild to moderate depression in post percutaneous coronary intervention patients. J Affect Disord. 2014;155:216-222.
Patients with coronary artery disease (CAD) often have depression, which increases their risk of mortality. Percutaneous coronary intervention (PCI), also known as coronary angioplasty, is a non-surgical procedure used to open narrowed coronary arteries. It is well tolerated and the most commonly used CAD treatment option; however, there is some evidence that suggests there is a higher incidence of depression among patients who have had a PCI than those treated with other therapies. While experience demonstrates that conventional antidepressant drugs are effective in patients with CAD who have major depressive disorder (MDD), the drugs do not convey long-term benefits in reducing mortality, may interact with CAD medications, and have adverse effects that can aggravate symptoms of CAD and decrease quality of life. Several clinical trials have reported that saffron (the dried stigma of Crocus sativus, Iridaceae) aqueous-alcohol extract can improve depression, and animal and human studies suggest it also may have cardioprotective effects. The purpose of this randomized, double-blind, controlled study was to compare the safety and antidepressant efficacy of saffron with that of fluoxetine — a commonly used pharmaceutical antidepressant originally sold as Prozac® — in treating depression in patients who have undergone PCI.
Patients (n=40; aged 20-65 years) were recruited from the Psychiatric Clinic of Tehran Heart Center in Tehran, Iran. Included patients had a PCI in the last six months, were diagnosed with mild-to-moderate MDD according to the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision (DSM-IV-TR™) criteria, and had a Hamilton Depression Rating Scale (HDRS) score of 14-22. Excluded patients were the following: those who had any other psychiatric disorder; had a high risk for suicide; received psychotropic agents, alternative medicine, or psychotherapy within four weeks, or electroconvulsive therapy within eight weeks prior to study entry; had substance abuse/dependence within the previous three months; had serious or life-threatening illness, thyroid disease, hepatic dysfunction, or renal dysfunction; had hypersensitivity to fluoxetine or herbal compounds; or pregnancy/lactation, oral contraception use, or the desire to get pregnant during the study. Out of the 74 patients originally recruited for the study, 40 met inclusion criteria and were enrolled in the trial.
Patients initially received either 20 mg/day fluoxetine or 15 mg/day saffron extract (SaffroMood®; Impiran Company; Tehran, Iran). The dried 80% ethanol saffron extract was standardized using a spectrophotometric method to measure safranal and crocin values expressed as direct reading of absorbance at about 330 and 440 nm, respectively. According to the study authors, “[e]ach [15 mg saffron] capsule contained 0.13-0.15 mg of safranal and 1.65-1.75 mg of crocin.”
Treatment doses were slowly titrated up; by week three, patients received the maximum dose of either 40 mg/day fluoxetine or 30 mg/day saffron extract. Synthetic essence of saffron aroma was added to the fluoxetine capsules to maintain blinding. The primary endpoint was the mean decrease in HDRS score from baseline to week six. (HDRS is a 17-item questionnaire that evaluates the severity of depression symptoms.) The a priori complete response rate was designated as ≥ 50% decrease in HDRS score, partial response rate was a 49% to 25% decrease in HDRS, and remission was considered an HDRS score of seven or less.
Baseline data were similar between groups. At three weeks and six weeks, there was no significant difference between groups in the reduction of HDRS scores. Both groups had a remission rate of 70% at the end of six weeks. A complete response occurred in 85% of patients in the saffron group and 80% of the patients in the fluoxetine group (P=0.67). Two patients in the saffron group had no treatment response (P=0.14), while all patients in the fluoxetine group responded to treatment. The study was well blinded based on the finding that most patients did not correctly guess which treatment they received.
No serious adverse events (AEs), as defined in the article, were reported by participants in either group. However, two patients in the fluoxetine group were excluded from the study due to severe anxiety and suicidal thoughts, and their treatment plans were adjusted. The six AEs reported by those who completed the study were mild and resolved spontaneously. There was no significant difference in the frequency of AEs between groups. The authors hypothesized that a longer study duration would likely show a greater frequency of AEs in the fluoxetine group than the saffron group.
The authors point out that the major limitations of the study were the small sample size and short duration (especially in light of the relatively high placebo response rate observed in short-term depression trials). In addition, the results cannot be generalized to patients with other cardiovascular disorders or treatment histories. According to the authors, longer-term studies in larger populations are needed to accurately compare the incidence of AEs in these two treatment groups, and the “long-term efficacy and safety of saffron as well as its optimal dosing requires further investigations.”
The authors conclude that short-term treatment with saffron is as effective as fluoxetine in patients who have undergone PCI resulting in mild-to-moderate MDD. Considering the negative cardiovascular effects observed with fluoxetine and the potential cardioprotective properties of saffron, it is suggested that future studies should also evaluate cardiovascular effects.
—Heather S. Oliff, PhD