Lopresti AL, Maes M, Maker GL, Hood SD, Drummond PD. Curcumin for the treatment of major depression: a randomised, double blind, placebo controlled study. J Affect Disord. 2014 Oct;167:368-375.
This was an 8-week, randomized, double-blind, placebo-controlled clinical trial. This study enrolled 56 patients with major depressive disorder (MDD), and all patients were randomly and equally allocated to be treated with either curcumin (500 mg twice daily; BCM-95 curcumin from Arjuna Natural Extracts, Kochi, India) or placebo for 8 weeks.
The inclusion and exclusion criteria for including patients in the study were as follows. Included were both male and female participants aged 18 to 65 years if they met the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition criteria for current major depressive disorder and had an Inventory of Depressive Symptomatology self-rated version (IDS-SR30) score of 14 or above. Only nonsmokers and volunteers not currently taking turmeric/curcumin supplements were included in the study. If participants were taking any pharmaceutical antidepressants, the drug dosage or type must have been stable for the previous 8 weeks and throughout the duration of the study. If volunteers were receiving psychological therapy, the treatment must have commenced at least 8 weeks prior to participating in the study.
The exclusion criteria disqualified participants with a psychotic disorder, bipolar disorder, comorbid obsessive-compulsive disorder, posttraumatic stress disorder, eating disorder, or any substance abuse or dependence disorder, as were participants assessed as having high risk of suicide. Volunteers were also excluded if they suffered from medical illnesses including diabetes, autoimmune diseases, cardiovascular disease, hypertension, neurodegenerative disorders (eg, Alzheimer’s disease, Parkinson’s disease, stroke, and multiple sclerosis), chronic fatigue syndrome, fibromyalgia and asthma; were pregnant or intended to become pregnant; currently breastfeeding; had suffered from an infection or illness over the past month; were currently taking any antiplatelet or anticoagulant medications; or had been diagnosed with any coagulation disorder.
The primary endpoint measured was the IDS-SR30. Secondary outcomes included IDS-SR30 factor scores and the Spielberger State-Trait Anxiety Inventory (STAI).
During the first 4 weeks of the clinical trial, patients treated with both curcumin and placebo demonstrated significant improvements in IDS-SR30 total score and most secondary outcome measures related to STAI. However, during the next 4 weeks (weeks 4 through 8), curcumin emerged as significantly more potent than placebo in improving several mood-related symptoms and showed a significant improvement for IDS-SR30 total score and mood score, along with a nonsignificant trend for STAI trait score. In addition, while examining the effects of curcumin in people with atypical depression, which is generally more difficult to treat, BCM-95 curcumin had even greater antidepressant and antianxiety efficacy compared to placebo. The study concluded that antiinflammatory effects of curcumin may account for its increased effectiveness in patients with depression and that this nutraceutical may provide a safe and effective treatment for individuals suffering with a major psychiatric disorder.
Limitations and Practice Implications
This study provides unequivocally convincing clinical evidence for the effective use of curcumin as an antidepressant. As acknowledged by the authors themselves, the potential limitations of the study were recruitment of a small cohort of patients and relatively short treatment duration. Nonetheless, this study yet again highlights that curcumin offers a safe, inexpensive, and potent treatment option for individuals suffering from MDD and atypical depression.
One of the most provocative aspects of this study was that curcumin treatment not only benefitted patients with major depression, but it significantly enhanced antidepressant and anxiolytic efficacy in people with atypical depression.
MDD is a common debilitating psychiatric disorder that affects nearly 16% to 20% of the population in both developed and developing nations.1,2 According to the World Health Organization, by the year 2020, major depression will become the second most prevalent cause of illness-induced disability worldwide.3,4 About 1 in 10 Americans report symptoms of depression, and this illness is responsible for the majority of almost 40,000 suicides per year in the United States. Depressed mood, anhedonia, and reduced energy levels are believed to be the core symptoms of depression, and presence of at least 2 of these symptoms is required for a confirmatory diagnosis of an individual suffering from MDD.
Antidepressants, ranging from monoamine oxidase inhibitors to recently developed selective serotonin reuptake inhibitors and selective norepinephrine reuptake inhibitors, are prescribed for alleviating the symptoms of depression. Ironically, in spite of the availability of these blockbuster molecules, as many as 30% of MDD patients do not even respond to these drug therapies in the first place, and the remaining 70% fail to achieve complete remission.5 Even when they provide some benefit, these drugs are truly only effective and safe in the short term. When taken long term, these synthetic antidepressants often associate with a plethora of side effects including sedation, weight gain, physical sensations of numbness or pain, and a propensity for abuse.
The role of immune activation in MDD was for the first time reported more than 20 years ago,6 and since then, it has become apparent that chronic inflammation plays a major role in this psychiatric illness.7 Meta-analyses of studies have revealed that increased peripheral blood levels of various cytokines, interleukin-6, tumor necrosis factor-alpha, and C-reactive protein are some of the key biomarkers of increased inflammation in depressed patients,8,9 and significant associations have been found between blood concentrations of these biomarkers and the severity of depression in individuals suffering from MDD.10,11 Inflammatory cytokines also interact with mitochondria to increase the reactive oxygen species production, which in turn increases cytokine expression.12 Taken together, these scientific findings clearly suggest that any treatment approach that can effectively combat inflammation and oxidative stress can have significant influence in alleviating MDD symptoms. Not surprisingly, there is an imperative need to develop novel approaches for the identification of more efficacious and safe drugs for the treatment of major depression.
The present study by Lopresti and colleagues is clearly a significant step forward in this direction because the authors have undertaken first ever, randomized, double-blind, placebo-controlled clinical trial to demonstrate that curcumin, the active compound in turmeric (Curcuma longa), has a significant antidepressive effect vis-à-vis placebo treatment in individuals suffering from MDD. These results also support a previous study that demonstrated that curcumin was equally effective as the pharmaceutical antidepressant fluoxetine (Prozac) for the treatment of depression.13 One of the most provocative aspects of this study was that curcumin treatment not only benefitted patients with major depression, but it significantly enhanced antidepressant and anxiolytic efficacy in people with atypical depression—a condition that involves much higher levels of inflammation and is much more difficult to treat.
Another important point worth noting about this study was that the researchers used a very specific type of curcumin, BCM-95, which has unique specifications, including high absorption and inclusion of turmeric essential oil not found in standard curcumin. Therefore, one must be cautious that the results may not be reproducible when using other forms of curcumin.
The observations made in this article build upon the well-established antiinflammatory and antioxidant activity of curcumin, as this naturally occurring Ayurvedic medicine has been used for healing mania and depression-related conditions for centuries.14-17 Although the precise mechanisms underlying the antidepressant effects of curcumin are not fully understood, it is hypothesized that it acts by inhibiting the monoamine oxidase enzyme and modulating the release of serotonin and dopamine. Moreover, preclinical studies in animal models have shown that curcumin enhances neurogenesis, notably in the frontal cortex and hippocampal regions of the brain.18-21
Some may argue that the sample size of the present study was small and the treatment duration with curcumin was relatively short. However, both of these potential limitations could be easily addressed in follow-up studies. Nonetheless, this was a randomized, double-blind, placebo-controlled study with a clearly unbiased study design, which highlights the potential clinical usefulness of curcumin in the treatment of individuals suffering with depression. These data without a doubt underscore the notion that curcumin has reached a stage where its efficacy is no longer considered a myth, especially in view of the depth and breadth of the scientific and clinical body of literature supporting its safe, inexpensive, and potent use in treating a myriad of inflammatory diseases, including depression in humans.
- Wong ML, Licinio J. Research and treatment approaches to depression. Nat Rev Neurosci. 2001;2(5):343-351.
- Wong ML, Licinio J. From monoamines to genomic targets: a paradigm shift for drug discovery in depression. Nat Rev Drug Discov. 2004 Feb;3(2):136-51.
- Ferrari AJ, Charlson FJ, Norman RE, et al. Burden of depressive disorders by country, sex, age, and year: findings from the global burden of disease study 2010. PLoS Med. 2013 Nov;10(11):e1001547.
- Ferrari AJ, Somerville AJ, Baxter AJ, et al. Global variation in the prevalence and incidence of major depressive disorder: a systematic review of the epidemiological literature. Psychol Med. 2013;43(3):471-481.
- Kato M, Chang CM. Augmentation treatments with second-generation antipsychotics to antidepressants in treatment-resistant depression. CNS Drugs. 2013;27 Suppl 1:S11-S19.
- Maes M, Bosmans E, Suy E, Vandervorst C, De Jonckheere C, Raus J. Immune disturbances during major depression: upregulated expression of interleukin-2 receptors. Neuropsychobiology. 1990;24(3):115-120.
- Maes M, Smith R, Scharpe S. The monocyte-T-lymphocyte hypothesis of major depression. Psychoneuroendocrinology. 1995;20(2):111-116.
- Zorrilla EP, Luborsky L, McKay JR, et al. The relationship of depression and stressors to immunological assays: a meta-analytic review. Brain Behav Immun. 2001;15(3):199-226.
- Dowlati Y, Herrmann N, Swardfager W, et al. A meta-analysis of cytokines in major depression. Biol Psychiatry. 2010;67(5):446-457.
- Meyers CA, Albitar M, Estey E. Cognitive impairment, fatigue, and cytokine levels in patients with acute myelogenous leukemia or myelodysplastic syndrome. Cancer. 2005;104(4):788-793.
- Motivala SJ, Sarfatti A, Olmos L, Irwin MR. Inflammatory markers and sleep disturbance in major depression. Psychosom Med. 2005;67(2):187-194.
- Sprague AH, Khalil RA. Inflammatory cytokines in vascular dysfunction and vascular disease. Biochem Pharmacol. 2009;78(6):539-552.
- 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.
- Goel A, Jhurani S, Aggarwal BB. Multi-targeted therapy by curcumin: how spicy is it? Mol Nutr Food Res. 2008;52(9):1010-1030.
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- Wang R, Xu Y, Wu HL, et al. The antidepressant effects of curcumin in the forced swimming test involve 5-HT1 and 5-HT2 receptors. Eur J Pharmacol. 2008;578(1):43-50.
- Xu Y, Ku BS, Yao HY, et al. The effects of curcumin on depressive-like behaviors in mice. Eur J Pharmacol. 2005;518(1):40-46.
- Xu Y, Ku BS, Yao HY, et al. Antidepressant effects of curcumin in the forced swim test and olfactory bulbectomy models of depression in rats. Pharmacol Biochem Behav. 2005;82(1):200-206.
- Xu Y, Ku B, Tie L, et al. Curcumin reverses the effects of chronic stress on behavior, the HPA axis, BDNF expression and phosphorylation of CREB. Brain Res. 2006;1122(1):56-64.