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Curcumin for the treatment of major depression.

Curcumin for the treatment of major depression

Lopresti AL, Maes M, Maker GL, Hood SD, Drummon PD. 2014. Curcumin for the treatment of major depression: A randomised, double-blind, placebo controlled study. J Affect Disord_167:368-75 doi: 10.1016/j.jad.2014.06.001

The understanding of major depressive disorder (MDD) has increased over recent years, with causative biological disturbances expanding from monoaminergic transmission, particularly serotonin availability, to also include dysregulation in the hypothalamus-pituitary-adrenal (HPA) axis, activation of immune-inflammatory pathways, increased oxidative and nitrosative stress, neuroprogression and mitochondrial dysfunction. Consequently, compounds that act upon these pathways have generated interest in the treatment of major depression.

Curcumin, the main bioactive component of Curcuma longa (turmeric) has been found to influence a number of these pathways. Specifically, it can lower markers of oxidative stress as a potent antioxidant, modulates immune-inflammation by acting as a cox-2 inhibitor and lowering pro-inflammatory cytokines, provides significant neuroprotection, modulates HPA activity, and influences monoamine transmission through an effect on serotonergic and dopaminergic activity. The current study aimed to expand the investigation into the antidepressant effects of curcumin supplementation in people with MDD.

This Australian study was a randomised, double blind, placebo controlled trial in which 56 individuals aged 18-65 years with MDD were treated with curcumin (500mg twice daily) or placebo for 8 weeks. The curcumin contained total curcuminoids 88% (curcumin, bisdemethoxycurcumin, demethyoxycurcumin) and volatile oils 7% from Curcuma longa Linn rhizomes. Use of pharmaceutical antidepressants provided the participant had been on a stable dose and type for eight weeks, the contraceptive pill and no more than once weekly use of analgesics were permitted. Concurrent psychological therapy was also permitted if the treatment was commenced at least 8 weeks prior to participating in the study. Exclusion criteria included psychotic disorders, posttraumatic stress disorder, eating disorder, substance abuse or dependence disorder, high suicide risk, a variety of medical illnesses, pregnancy or intention to fall pregnant, breastfeeding, illness or infection in previous month, antiplatelet or anticoagulation medications or diagnosis of any coagulation disorder.

The primary measure of efficacy was assessed using the self-reporting questionnaire, Inventory of Depressive Symptomatology self-rated version (IDS-SR30), containing 30 items measuring depressive symptoms based on the DSM-IV criteria with regards to frequency and severity of the previous 7 days. The IDS scores were also categorised into 'mood/cognition' factor representing affective and cognitive symptoms (IDSm) and 'anxiety/ arousal' factor indicating arousal and somatic complaints (IDSa). Additionally, the self-reported Spielberger State-Trait Anxiety Inventory (STAI) was used for assessing anxiety. Questionnaires were completed prior to randomisation (baseline), at weeks 4 and 8.

The study found that across the 8-week trial, treatment with both curcumin and placebo resulted in significant changes in IDS and STAI scores, with no significant difference in improvements between the groups. Reviewing the changes over time from baseline to week 4, and week 4 to week 8 however provided more insight. Both the placebo and curcumin groups experienced significant and equivalent changes in the IDS scores from baseline to week 4, with the curcumin group also demonstrating significant changes in the IDS sore and IDSm scores for weeks 4-8. No significant changes were observed in the placebo group for this time period. Additionally, trait STAI scores were significantly improved from weeks 4-8 for the curcumin group, with no such changes observed in the placebo group. The results demonstrate that while curcumin and placebo were equally effective in reducing symptoms of depression and anxiety in the first four weeks of treatment, curcumin provided longer, ongoing effects being significantly more effective than placebo at lowering self-reported depressive and anxiety symptoms from weeks 4-8 of treatment. When participants were categorised into 'melancholic' or 'atypical' depression subgroups based on their baseline IDS questionnaires, curcumin was seen to have an even greater efficacy compared to placebo in the atypical subgroup.

The authors suggested that the overall lack of greater efficacy of curcumin compared to placebo could be due to a lack of antidepressant activity of curcumin, inadequate dose used, the placebo response of the first month masking the positive benefit or that the antidepressant effects of curcumin make not begin to act until after four weeks of treatment. The relatively small sample sizes of the study may have resulted in an inadequately powered study and limit the reliability of the findings.

This is the third clinical study to investigate the effects of curcumin/turmeric in humans with MDD. In the first study, curcumin in comparison to placebo was investigated as an add-on therapy to newly commenced antidepressant medication (venlafaxine XR or escitalopram) at a dose of 500mg/day for five weeks finding curcumin comparable to placebo. The second study (summarised in the AJHM 26(3)) compared treatment for 6 weeks of curcumin alone (500mg twice daily), fluoxetine alone (20mg/day) or a combination of fluoxetine (20mg/day) plus curcumin (500mg/day) and found significant improvements in depressive symptoms for all three interventions. The differences in these past results and the current study highlight the need for more quality research for curcumin in the treatment of MDD. Specifically, clinical trials of longer duration are warranted to assess the effect and efficacy of curcumin over a longer period of time, varied dosing regimes to understand the optimal dose, and larger study groups to elicit understanding of differences in responses in different categories of MDD such as atypical depression and in conjunction with different antidepressant therapies.
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Author:Tester, Jodie
Publication:Australian Journal of Herbal Medicine
Article Type:Report
Geographic Code:8AUST
Date:Dec 1, 2014
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