Elsevier

Journal of Affective Disorders

Volume 167, 1 October 2014, Pages 368-375
Journal of Affective Disorders

Research report
Curcumin for the treatment of major depression: A randomised, double-blind, placebo controlled study

https://doi.org/10.1016/j.jad.2014.06.001Get rights and content

Abstract

Background

Curcumin, the principal curcuminoid derived from the spice turmeric, influences several biological mechanisms associated with major depression, namely those associated with monoaminergic activity, immune-inflammatory and oxidative and nitrosative stress pathways, hypothalamus-pituitary-adrenal (HPA) axis activity and neuroprogression. We hypothesised that curcumin would be effective for the treatment of depressive symptoms in individuals with major depressive disorder.

Methods

In a randomised, double-blind, placebo-controlled study, 56 individuals with major depressive disorder were treated with curcumin (500 mg twice daily) or placebo for 8 weeks. The primary measure was the Inventory of Depressive Symptomatology self-rated version (IDS-SR30). Secondary outcomes included IDS-SR30 factor scores and the Spielberger State-Trait Anxiety Inventory (STAI).

Results

From baseline to week 4, both curcumin and placebo were associated with improvements in IDS-SR30 total score and most secondary outcome measures. From weeks 4 to 8, curcumin was significantly more effective than placebo in improving several mood-related symptoms, demonstrated by a significant group x time interaction for IDS-SR30 total score (F1, 53=4.22, p=.045) and IDS-SR30 mood score (F1, 53=6.51, p=.014), and a non-significant trend for STAI trait score (F1, 48=2.86, p=.097). Greater efficacy from curcumin treatment was identified in a subgroup of individuals with atypical depression.

Conclusions

Partial support is provided for the antidepressant effects of curcumin in people with major depressive disorder, evidenced by benefits occurring 4 to 8 weeks after treatment.

Limitations

Investigations with larger sample sizes, over extended treatment periods, and with varying curcumin dosages are required.

Introduction

Disturbances in monoaminergic neurotransmission, particularly around serotonin availability, were originally posited as the primary cause of major depression (Cowen, 2008). However, studies now confirm that major depression is associated with a large array of biological disturbances. These include dysregulation in the hypothalamus-pituitary-adrenal (HPA) axis, activation of immune-inflammatory pathways, increased oxidative and nitrosative stress, neuroprogression, and mitochondrial dysfunction (Leonard and Maes, 2012, Maes et al., 2011). Consequently, this has sparked interest in compounds that target these pathways. Examples include anti-inflammatory treatments influencing immuno-inflammation such as cyclooxygensase-2 (COX-2) inhibitors, aspirin, minocycline and polyunsaturated fatty acids (Berk et al., 2013a, Fond et al., 2014, Muller, 2013) and antioxidant therapies to increase antioxidant defences and lower free radical damage such as n-acetyl cysteine, Ebselen, vitamin E and coenzyme-Q10 (Berk et al., 2013b, Scapagnini et al., 2012). Interestingly, despite pharmaceutical antidepressants originally being heralded as targeting monoaminergic actions, there is also evidence that they can modulate immuno-inflammation, reduce oxidative stress, enhance neurotrophic factors and influence HPA activity (Abdel-Wahab and Salama, 2011, Andrade and Rao, 2010, Hannestad et al., 2011, Kocki et al., 2012, Schule, 2007).

Curcumin is the most active compound of the Indian spice turmeric and comprises 2–8% of most turmeric preparations (Sharma et al., 2005). Curcumin [1,7-bis-(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione] is a low molecular weight polyphenol, first chemically characterised in 1910 by Milobedzka et al. (1910) and influences all of the aforementioned biological mechanisms (Aggarwal and Harikumar, 2009, Lopresti et al., 2012). More specifically, curcumin is a potent antioxidant that can lower markers of oxidative stress (Naik et al., 2011, Rai et al., 2010), modulate immuno-inflammation by acting as a COX-2 inhibitor (Lee et al., 2011, Plummer et al., 1999) and lower pro-inflammatory cytokines (Basnet and Skalko-Basnet, 2011, Belcaro et al., 2010), provide significant neuroprotection (Huang et al., 2011, Xu et al., 2007), modulate HPA activity (Huang et al., 2011, Li et al., 2009) and influence monoamine transmission through its effect on serotonergic and dopaminergic activity (Bhutani et al., 2009, Kulkarni et al., 2008, Xia et al., 2007). In animal studies, antidepressant effects of curcumin have been attributed to its serotonergic, dopaminergic, neuroprotective and HPA-modulating effects (Huang et al., 2011, Kulkarni et al., 2008, Xu et al., 2006). Two clinical trials have also now been completed investigating the antidepressant effects of curcumin in people with major depression. In the first study, curcumin as an add-on to antidepressant therapy did not enhance treatment outcome (Bergman et al., 2013), whereas in the second trial curcumin demonstrated similar antidepressant efficacy to fluoxetine (Sanmukhani et al., 2014). However, the latter study lacked a placebo-control and volunteers were not blinded.

The purpose of this study was to expand investigation into the antidepressant effects of curcumin supplementation in people with major depressive disorder. It was hypothesised that treatment with curcumin would lead to greater antidepressant benefits than a placebo, reflected by reductions in the administered depression and other mood-related self-report questionnaires. Curcumin was also hypothesised to have greater benefits for participants with atypical depression as it is associated with dysregulated immune-inflammatory pathways (Hickman et al., 2014, Lamers et al., 2013).

Section snippets

Study design

This study was an 8-week, randomised, double-blind, placebo-controlled clinical trial (Fig. 1). The trial protocol was approved by the Human Research Ethics Committee at Murdoch University, Western Australia. The trial was registered with the Australian New Zealand Clinical Trials Registry (no. 12612001260819) and participants were recruited between February and November 2013, across the Perth, Western Australia metropolitan area. Recruitment occurred through advertisements and promotions in

Baseline questionnaire and demographic information

Seventy-seven people were screened for participation in the study and 56 met inclusion/exclusion criteria and were enrolled to participate. Twenty-eight people were randomised into the placebo group and 28 into the treatment (curcumin) group. Fifty-two participants completed up to week 8. There were 4 drop-outs, one from the placebo group and three from the curcumin group, with no significant difference between the dropout rate in each group. Reasons for withdrawal included an unexpected visit

Discussion

The results of this study provide partial support for the antidepressant and anxiolytic effects of curcumin in people suffering from major depressive disorder. While curcumin and placebo were equally effective in reducing depressive and anxiety symptoms in the first four weeks of treatment, curcumin was significantly more effective than placebo in lowering self-reported depressive and anxiety symptoms from weeks 4 to 8. When examining the effects of curcumin in people with atypical depression,

Limitations and directions for future research

The relatively small samples size used in this study limits the reliability and statistical power associated with the findings. For evaluation of curcumin׳s antidepressant effects, data from approximately 50 participants was obtained. Sample sizes were even lower when evaluating the effects of curcumin on people with atypical depression. The results from this study therefore require replication with larger sample sizes.

In this study, a high proportion (approximately 70%) of participants

Conflict of interest

This study was supported in part by a grant from Arjuna Natural Extracts Limited to Murdoch University.

The authors report no biomedical financial interests or potential conflicts of interest.

Role of funding source

Financial assistance for this study was provided by Arjuna Natural Extracts Limited.

Acknowledgements

The authors acknowledge the gracious help of Arjuna Natural Extracts Limited for providing curcumin capsules and financial assistance to conduct the study. We also acknowledge infrastructure support provided by NCRIS BioPlatforms Australia.

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