Reviewed: Al-Karawi D, Al Mamoori DA, Tayyar Y. The role of curcumin administration in patients with major depressive disorder: Mini meta-analysis of clinical trials. Phytother Res. 2016;30(2):175-183.

Nearly 50% of patients with major depressive disorder (MDD) discontinue treatment due to adverse events. Therapies with better tolerability are needed to treat this chronic disease that negatively affects quality of life and increases morbidity. The antidepressant activity of curcumin, a chemical constituent of turmeric (Curcuma longa, Zingiberaceae) rhizome, has been evaluated in numerous clinical trials. This meta-analysis evaluated the safety and efficacy of curcumin in the treatment of MDD.

The search of the literature and presentation of the results followed the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). The following databases were searched from 1986 through 2016: PubMed, Scopus, PsycINFO, Evidence-Based Medicine Guidelines, DynaMed, JAMAevidence, and the Cochrane Library. The following key words were used: curcumin, depression, MDD, efficacy, and effect. Reference lists of identified papers were hand-searched. Included articles met the following criteria: (1) human study, (2) quantitative analysis, (3) intervention and control group, (4) curcumin was an independent intervention, (5) study addressed only MDD, (6) depression was measured with standardized scales, and (7) the study was published in English. The Quality Assessment Tool for Quantitative Studies was used to assess study quality and an overall rating of methodological quality was assigned. This rating system classifies studies as strong (no weak ratings), moderate (one weak rating), or weak (two or more weak ratings). For the meta-analysis, the data from all studies were converted into Hamilton Depression Rating Scale scores according to published methods. Small sample sizes were adjusted with the Hedges’ adjusted g formulation of standardized difference in means. The random-effects model and generic inverse variance method were used to combine the results since the studies had different design characteristics.

A total of 1,757 studies were identified, and six met all inclusion criteria (four randomized controlled trials, one crossover study, and one open-label study).^1-6 The six studies included a total of 342 patients (n = 177, curcumin; n = 165, control). All patients received antidepressant therapy in addition to either curcumin (1,000 mg per day in five studies or 500 mg per day in one study) or placebo. In regard to methodological quality, five were rated as strong, and one was rated as moderate. The meta-analysis showed a significant reduction in MDD symptoms with curcumin treatment compared with control (P = 0.002). This outcome was not influenced by any single study. Several subgroup analyses were conducted with the following outcomes: (1) curcumin had a significant benefit in middle-aged patients (P = 0.002) but not older-aged patients (specific age ranges not described); (2) curcumin had a significant benefit in patients treated for more than six weeks (P = 0.001), but not patients treated for less than six weeks; (3) the 1,000 mg per day of curcumin had a significant benefit (P = 0.002), but the 500 mg per day did not; and (4) curcumin had a significantly greater benefit in patients with MDD only compared with patients with MDD plus comorbidities (P = 0.001).

In two of the studies,^4-5 researchers used BCM-95 (Arjuna Natural Extracts Ltd.; Aluva, Kerala, India), a standardized preparation of curcuminoids blended with the essential oil of turmeric. In three of the studies,^1-3 the curcumin treatment also contained piperine, a chemical constituent of black pepper (Piper nigrum, Piperaceae) fruit that has been shown to increase the bioavailability of curcumin. The authors of the meta-analysis provided no further descriptions of the curcumin preparations used in the six studies. Subgroup analysis showed that treatments containing piperine had smaller benefits than curcumin alone (P = 0.05). However, the authors note that two of these studies used a low (potentially subtherapeutic) dose of piperine, and the study that used a higher dose of piperine used a low dose of curcumin (which may have been too low to produce an effect). Therefore, the piperine meta-analysis should be viewed with caution.

The pooled data had minimal heterogeneity as assessed with the I2 index. Funnel plot analysis showed no publication bias. Adverse events were digestive/gastrointestinal complaints (e.g., gastritis, nausea), tachycardia, flushing, and giddiness. Two of the six studies reported no adverse events; adverse effects in the placebo groups were not reported.

According to the authors, this is the first meta-analysis of the effect of curcumin on MDD. The authors conclude that curcumin is effective in reducing symptoms of depression in patients with MDD who are taking antidepressants. They also note that curcumin is more effective in middle-aged patients, at a dose of 1,000 mg per day, and when taken for more than six weeks. The authors acknowledge that the results should be interpreted with caution because only six studies were included and only two doses of curcumin preparations were evaluated. They also acknowledge that the dose of piperine and/or curcumin may not have been optimal, and  that long-term outcomes were not assessed despite that MDD is a chronic condition.

The authors used rigorous methodology in conducting the meta-analysis. These encouraging results indicate that larger and longer-duration clinical trials of curcumin in the treatment of MDD are warranted. There were no conflicts of interest.

—Heather S. Oliff, PhD

References

1. Bergman J, Miodownik C, Bersudsky Y, et al. Curcumin as an add-on to antidepressive treatment: a randomized, double-blind, placebo-controlled, pilot clinical study. Clin Neuropharmacol. 2015;36(3):73-77.
2. Esmaily H, Sahebkar A, Iranshahi M, et al. An investigation of the effects of curcumin on anxiety and depression in obese individuals: a randomized controlled trial. Chin J Integr Med. 2015;21(5):332-338.
3. Panahi Y, SadeEi R, Karami GR, Sahebkar A. Investigation of the efficacy of adjunctive therapy with bioavailability-boosted curcuminoids in major depressive disorder. Phytother Res. 2015;29:17-21.
4. Lopresti AL, Maes M, Maker GL, Hood SD, Drummond PD. Curcumin for the treatment of major depression: a randomized, double-blind, placebo controlled study. J Affect Disord. 2014;167:368-375.
5. Sanmukhani J, Satodia V, Trivedi J, et al. Efficacy and safety of curcumin in major depressive disorder: a randomized controlled trial. Phytother Res. 2014;28(4):579-585.
6. Yu JJ, Pei LB, Zhang Y, Wen ZY, Yang JL. Chronic supplementation of curcumin enhances the efficacy of antidepressants in major depressive disorder: a randomized, double-blind, placebo-controlled pilot study. J Clin Psychopharmacol. 2015;35(4):406-410.