Elsevier

Journal of Affective Disorders

Volume 207, 1 January 2017, Pages 188-196
Journal of Affective Disorders

Efficacy of curcumin, and a saffron/curcumin combination for the treatment of major depression: A randomised, double-blind, placebo-controlled study

https://doi.org/10.1016/j.jad.2016.09.047Get rights and content

Highlights

  • Curcumin and saffron effective for the treatment of depression.

  • Curcumin and saffron effective in reducing anxiety in depressed adults.

  • Varying doses had no effect on outcome.

  • Curcumin and saffron have greater efficacy for atypical depression.

Abstract

Background

Several studies have supported the antidepressant effects of curcumin (from the spice turmeric) and saffron for people with major depressive disorder. However, these studies have been hampered by poor designs, small sample sizes, short treatment duration, and similar intervention dosages. Furthermore, the antidepressant effects of combined curcumin and saffron administration are unknown.

Methods

In a randomised, double-blind, placebo-controlled study, 123 individuals with major depressive disorder were allocated to one of four treatment conditions, comprising placebo, low-dose curcumin extract (250 mg b.i.d.), high-dose curcumin extract (500 mg b.i.d.), or combined low-dose curcumin extract plus saffron (15 mg b.i.d.) for 12 weeks. The outcome measures were the Inventory of Depressive Symptomatology self-rated version (IDS-SR30) and Spielberger State-Trait Anxiety Inventory (STAI).

Results

The active drug treatments (combined) were associated with significantly greater improvements in depressive symptoms compared to placebo (p=.031), and superior improvements in STAI-state (p<.001) and STAI-trait scores (p=.001). Active drug treatments also had greater efficacy in people with atypical depression compared to the remainder of patients (response rates of 65% versus 35% respectively, p=.012). No differences were found between the differing doses of curcumin or the curcumin/saffron combination.

Limitations

Investigations with larger sample sizes are required to examine the efficacy of differing doses of curcumin and saffron/curcumin combination. Its effects in people with atypical depression also require examination in larger scale studies.

Conclusions

Active drug treatments comprising differing doses of curcumin and combined curcumin/saffron were effective in reducing depressive and anxiolytic symptoms in people with major depressive disorder.

Introduction

Major depressive disorder affects 6–8% of adults every year, and has a lifetime prevalence of 15–20% (Gelenberg, 2010, Richards, 2011). It is a disabling condition that has adverse effects on personal, social, occupational, and educational function. Depression is also associated with significant medical difficulties as there is a greater risk of mortality from all causes in people with depression compared to their non-depressed counterparts (Kozela et al., 2016). In fact, according to the World Health Organization (WHO, 2008), depression is the leading cause of disability as measured by Years Lived with a Disability and the fourth leading contributor to the global burden of disease. In a recent examination of a cohort of Danish adults, depression was associated with a reduced life expectancy of 14 years in men and 10 years in women (Laursen et al., 2016).

Major depressive disorder is primarily treated with psychological and/or pharmacological therapies, with research suggesting similar rates of efficacy (Sinyor et al., 2010). Unfortunately, these rates are far from ideal as approximately 60–80% of people do not obtain full symptom remission (Sinyor et al., 2010, Warden et al., 2007). Pharmacological interventions are also associated with several adverse effects that contribute to their early discontinuation (Goethe et al., 2007).

Interest in alternative and complementary therapies is high, as evidenced by a 2007 study confirming almost 50% of women with depression used complementary and alternative medicine over a one year period (Wu et al., 2007). In a more recent study of adults with bipolar disorder, 29% had used a dietary supplement for at least 7 days, and 20% used a supplement long term (Bauer et al., 2015). A commonly cited reason for their use relates to their perceived safety profile. Unfortunately, high-quality research on many herbal and nutraceutical therapies for depression is limited, reinforcing the need for ongoing research.

Curcumin, derived from the spice turmeric, and saffron (Crocus sativus L.), are two commonly used spices that have been increasingly investigated for their antidepressant effects. In recent meta-analyses and systematic reviews, it was concluded that curcumin (Al-Karawi et al., 2015) and saffron (Hausenblas et al., 2013, Lopresti and Drummond, 2014) were more effective than placebo for the treatment of major depressive disorder. In several studies, saffron's antidepressant effects were also found to be similar to the antidepressant medications fluoxetine (Akhondzadeh Basti et al., 2007, Noorbala et al., 2005, Shahmansouri et al., 2014) and imipramine (Akhondzadeh et al., 2004). However, further research is warranted, particularly in determining optimal treatment dosages and length of treatment. Thus far, no study has been longer than 8 weeks, and investigated doses have often been similar across studies.

In previous studies on the antidepressant effects of curcumin extracts, a daily dose of 500 mg b.i.d. has most commonly been used. We sought to determine whether a lower dose comprising 250 mg b.i.d. would have similar antidepressant and anxiolytic efficacy. In addition, our aim was to investigate whether saffron augmented the antidepressant effect of curcumin. Both of these compounds appear to have similar antidepressant biological mechanisms of action, namely through their anti-inflammatory, antioxidant, monaminergic, hypothalamus-pituitary-adrenal (HPA) modulating, and neuroprotective effects (Lopresti and Drummond, 2014, Lopresti et al., 2012). However, saffron also contains four major bioactive compounds, crocins, crocetin, picrocrocin and safranal, which are believed to contribute to its antidepressant activity. We hypothesized that the combination of saffron and curcumin, with its broader profile of active constituents, would lead to enhanced antidepressant and anxiolytic effects.

Our aim was also to investigate the symptomatic effects and safety profile of these spices over a 12-week period, making it the longest study to date on these ingredients for the treatment of major depression. As curcumin has shown particular promise in adults with atypical depression (Lopresti et al., 2014), its effects in participants with this subtype of depression were also examined.

Section snippets

Study design

This was a 12-week, randomised, double-blind, placebo-controlled clinical trial, with a 1-week, placebo run-in phase (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 (Trial ID. ACTRN12615000791538) and participants were recruited through social and print media advertisements between August 2015 and February 2016, across the Perth, Western

Baseline questionnaire and demographic information

309 people were screened for participation in the study and 160 met inclusion/ exclusion criteria and were enrolled to participate. All 160 participants were placed on placebo for one-week prior to randomisation into treatment conditions. Seven people failed to take capsules and/or complete repeat questionnaires after the first week, and 30 people experienced greater than a 30% change in IDS score following the 1-week, placebo, run-in phase, leaving data from 123 participants available for

Discussion

The results of this study add to the existing evidence on the beneficial antidepressant and anxiolytic effects of curcumin in people suffering from major depressive disorder. The addition of saffron to low-dose curcumin did not enhance treatment efficacy.

Compared to a placebo, the 12-week administration of active drug treatments comprising HDC, LDC, or LDC+S was associated with significantly greater improvements in depressive symptoms. A response rate (reduction of greater than 50% in

Conflict of Interest

All authors declare that they have no conflicts of interest.

Role of the funding source

Funding for this study was provided by Arjuna Natural Extracts Limited, Dolcas-Biotech LLT, and Health World Limited. These sponsors had no involvement in the study design; collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the article for publication.

Acknowledgements

The authors acknowledge the gracious help of Arjuna Natural Extracts Limited, Dolcas-Biotech LLT, and Health World Limited for providing curcumin/saffron capsules and financial assistance to conduct the study. We also acknowledge the support of our research assistants, Jennifer Anderson and Stephen Smith.

References (47)

  • N. Shahmansouri 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)
  • A. Talaei et al.

    Crocin, the main active saffron constituent, as an adjunctive treatment in major depressive disorder: a randomized, double-blind, placebo-controlled, pilot clinical trial

    J. Affect. Disord.

    (2015)
  • B.B. Aggarwal et al.

    Curcumin: an orally bioavailable blocker of TNF and other pro-inflammatory biomarkers

    Br. J. Pharmacol.

    (2013)
  • S. Akhondzadeh et al.

    Comparison of Crocus sativus L. and imipramine in the treatment of mild to moderate depression: a pilot double-blind randomized trial [ISRCTN45683816]

    BMC Complement. Altern. Med.

    (2004)
  • D. Al-Karawi et al.

    The role of curcumin administration in patients with major depressive disorder: mini meta-analysis of clinical trials

    Phytother. Res.

    (2015)
  • B. Antony et al.

    A pilot cross-over study to evaluate human oral bioavailability of BCM-95 CG (Biocurcumax), a novel bioenhanced preparation of curcumin

    Indian J. Pharm. Sci.

    (2008)
  • G. Belcaro et al.

    Efficacy and safety of Meriva(R), a curcumin-phosphatidylcholine complex, during extended administration in osteoarthritis patients

    Altern. Med. Rev.

    (2010)
  • J. Bergman et al.

    Curcumin as an add-on to antidepressive treatment: a randomized, double-blind, placebo-controlled, pilot clinical study

    Clin. Neuropharmacol.

    (2013)
  • H. Esmaily 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)
  • A.J. Gelenberg

    The prevalence and impact of depression

    J. Clin. Psychiatry

    (2010)
  • J.W. Goethe et al.

    Selective serotonin reuptake inhibitor discontinuation: side effects and other factors that influence medication adherence

    J. Clin. Psychopharmacol.

    (2007)
  • R.J. Hickman et al.

    C-reactive protein is elevated in atypical but not nonatypical depression: data from the National Health and Nutrition Examination Survey (NHANES) 1999–2004

    J. Behav. Med.

    (2013)
  • B.L. Kennedy et al.

    Assessment of state and trait anxiety in subjects with anxiety and depressive disorders

    Psychiatr. Q.

    (2001)
  • Cited by (0)

    View full text