|Date: 01-13-2017||HC# 121651-560|
Lopresti AL, Drummond PD. Efficacy of curcumin, and a saffron/curcumin combination for the treatment of major depression: A randomised, double-blind, placebo-controlled study. J Affect Disord. 2017;207:188-196.
The use of complementary and alternative medicines to treat depression is widespread, with as many as 50% of women diagnosed choosing these options. The antidepressant activity of curcumin, a component of turmeric (Curcuma longa, Zingiberaceae) rhizome, has been evaluated in numerous clinical trials, and saffron, the dried stigmata of Crocus sativus (Iridaceae), is used in traditional medicine to treat depression. Meta-analyses and systematic reviews indicate that turmeric and saffron are more effective than placebo for treating major depressive disorder (MDD). However, depression is a chronic condition, and according to the authors, there are no studies that evaluate turmeric or saffron for more than 8 weeks. They also point out that most published studies evaluate a similar dose; therefore, potentially more effective doses need to be evaluated. The authors hypothesize that turmeric and saffron taken together will have greater benefits. The purpose of this randomized, double-blind, placebo-controlled study was to evaluate the efficacy and safety of turmeric and saffron in patients with MDD in a 12-week study.
Patients (n = 123, aged 18-65 years) with MDD according to the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV) criteria were recruited via social media and print advertisements between August 2015 and February 2016 in Perth, Australia. Included patients had an Inventory of Depressive Symptomatology self-rated version (IDS-SR30) score ≥18. Exclusion criteria included the following: psychotic disorder, bipolar disorder, comorbid obsessive-compulsive disorder, posttraumatic stress disorder, eating disorder, any substance abuse or dependence disorder, diabetes, autoimmune diseases, cardiovascular disease, hypertension, neurodegenerative disorders (e.g., Alzheimer's disease, Parkinson's disease, stroke, and multiple sclerosis), chronic fatigue syndrome, fibromyalgia, asthma, coagulation disorder, pregnancy, plans to become pregnant, currently breastfeeding, an infection or illness during the previous month, and currently taking any antiplatelet or anticoagulant medications.
Patients were permitted to continue taking pharmaceutical antidepressants and herbal/vitamin supplements if the dose was stable for the previous 4 weeks and stable for the duration of the study. Patients could use the contraceptive pill, and analgesics ≤1x/week. After a 1-week placebo run-in phase, patients were randomly assigned to 1 of the 4 following treatments for 12 weeks: (1) placebo, (2) 500 mg/day curcumin (BCM-95®; DolCas Biotech [Landing, New Jersey] and Arjuna Natural Extracts Ltd [Kerala, India]), (3) 1000 mg/day curcumin (BCM-95), and (4) 500 mg/day curcumin (BCM-95) plus 30 mg/day saffron (affron®; Pharmactive Biotech Products, S.L.; Madrid, Spain). The primary outcome measure was the change in depressive symptoms according to the IDS-SR30. Anxiety was measured with the Spielberger State-Trait Anxiety Inventory (STAI), which measured "state" and "trait" symptoms. Assessments were made at baseline and weeks 4, 8, and 12. A treatment response was considered to be a reduction of >50% in depressive symptoms on IDS.
A total of 160 patients were enrolled and 37 were excluded after the placebo run-in. The placebo run-in phase was used to exclude patients who had a 30% change in IDS score. The 12-week study was completed by 111 patients who consumed >70% of capsules and completed all self-reported assessments. There were no significant differences in patient discontinuation rates; reasons for withdrawal included medication change, no response/lost to follow up, and inconsistent capsule intake. No patient withdrew due to adverse effects (AEs). There were no significant differences among groups in the frequency of AEs; however, there was a trend of increased diarrhea/loose bowels in the high-dose curcumin group and spicy aftertaste in both curcumin groups.
All groups had a significant decrease in IDS over time (P < 0.001); however, the placebo group significantly decreased only through week 4, while the other groups continued to decrease in IDS through week 12. This effect of time was significantly different between placebo and all other groups combined (P < 0.031). The IDS response rates were 13% in the placebo group, 28% in the high-dose curcumin group, 27% in the low-dose curcumin group, and 31% in the combination group. There were no significant differences in the IDS response rate among groups. All groups had a significant decrease in STAI-trait over time (P ≤ 0.001). Only the curcumin and curcumin/saffron groups had a significant decrease in STAI-state over time (P ≤ 0.002). This effect of time was significantly different between placebo and all other groups combined for both STAI-trait (P = 0.001) and STAI-state (P < 0.001). A subgroup analysis revealed that in patients with atypical depression (n = 34), all treatments combined were significantly more effective than placebo for IDS (P = 0.007), STAI-trait (P = 0.009), and STAI-state (P < 0.001). In addition, the IDS response rate was 65% in patients with atypical depression versus 35% in patients with other types of depression (P = 0.012).
The authors conclude that curcumin has beneficial antidepressant and anxiolytic effects, especially in patients with atypical depression. However, adding saffron to curcumin treatment did not improve efficacy, and there was no significant difference between the 2 doses of curcumin. Curcumin was well tolerated as evidenced by no patient dropouts due to AEs. The authors say that a limitation of the study is that it may have been underpowered to detect differences between curcumin doses because of the large dropout rate after the placebo run-in. Another limitation is that both assessments were self-rated rather than physician-rated. Antidepressants were used by 42-64% of the population. It is unclear how this may have impacted the study outcomes. Ideally, the population should have included only patients not taking antidepressant medications. While the authors conclude efficacy in patients with MDD, there was no significant difference in response rate, and the differences among groups were a factor of time rather than treatment. The effect in patients with atypical depression needs to be further evaluated. The curcumin/saffron capsules and funding for the study were provided by Arjuna Natural Extracts Ltd, DolCas Biotech, and Health World Limited (Queensland, Australia).—Heather S. Oliff, PhD