19 replies to this topic

[blood]

In this new study (see below) curcumin is found to be about as effective as a SSRI in treating major depression.

http://www.ncbi.nlm....pubmed/23832433

Phytother Res. 2013 Jul 6. doi: 10.1002/ptr.5025. [Epub ahead of print]

Efficacy and Safety of Curcumin in Major Depressive Disorder: A Randomized Controlled Trial.

Sanmukhani J, Satodia V, Trivedi J, Patel T, Tiwari D, Panchal B, Goel A, Tripathi CB.

Source
Department of Pharmacology, Government Medical College, Bhavnagar, Gujarat, India.

Abstract

Curcumin, an active ingredient of Curcuma longa Linn (Zingiberaceae), has shown potential antidepressant-like activity in animal studies. The objectives of this trial were to compare the efficacy and safety of curcumin with fluoxetine in patients with major depressive disorder (MDD). Herein, 60 patients diagnosed with MDD were randomized in a 1:1:1 ratio for six weeks observer-masked treatment with fluoxetine (20 mg) and curcumin (1000 mg) individually or their combination. The primary efficacy variable was response rates according to Hamilton Depression Rating Scale, 17-item version (HAM-D17 ). The secondary efficacy variable was the mean change in HAM-D17 score after six weeks. We observed that curcumin was well tolerated by all the patients. The proportion of responders as measured by the HAM-D17 scale was higher in the combination group (77.8%) than in the fluoxetine (64.7%) and the curcumin (62.5%) groups; however, these data were not statistically significant (P = 0.58). Interestingly, the mean change in HAM-D17 score at the end of six weeks was comparable in all three groups (P = 0.77). This study provides first clinical evidence that curcumin may be used as an effective and safe modality for treatment in patients with MDD without concurrent suicidal ideation or other psychotic disorders.


PMID: 23832433 [PubMed - as supplied by publisher]

The study made use of the BCM95 extract.

[ta5]

And here:
http://www.longecity...-in-depression/

[nowayout]

Given that fluoxetine has been shown to be about as effective as placebo for depression, this probably looks better than it really is.

But if this is a real effect and not placebo, it could be from curcumin's effect as an antiinflammatory or possibly also its estrogenic effect (hormone replacement therapy is also often effective for depression).

[blood]

And here:
http://www.longecity...-in-depression/

Sorry - I did search, but unfortunately missed your earlier thread.

[Godof Smallthings]

I do think there is a good chance curcumin IS helpful in depression, but it seems that this study was not double-blinded, so it is questionable if we can learn something from it.

If I am correct about the lack of double-blinding, there is both the cultural pride and cultural belief factor (turmeric is an ayurvedic herb and essential to Indian cooking) to take into account here, apart from the usual placebo effect caveats.

[niner]

The study was at least observer-blinded, so I don't see that as a huge problem. The real problem is that none of the results are statistically significant. With those giant P values, I don't see how they got it published. How are we to distinguish the results from random noise?

[gt35r]

"however, these data were not statistically significant (P = 0.58). Interestingly, the mean change in HAM-D17 score at the end of six weeks was comparable in all three groups (P = 0.77)"

[nowayout]

"however, these data were not statistically significant (P = 0.58). Interestingly, the mean change in HAM-D17 score at the end of six weeks was comparable in all three groups (P = 0.77)"

Oh jeez, meaning we can safely discount this study as crap.

[blood]

I think you folks are mis-reading the abstract. The researchers were comparing effects of three treatments. A statistically significant result would mean one or more of the treatments was more effective than the others (e.g., fluoxetine is more effective than curcumin, say). The non-significant result is the "news" - curcumin can't be distinguished from fluoxetine in terms of treatment effects.

Edited by blood, 26 August 2013 - 08:00 AM.

[Guardian4981]

Curcumin is an MAO B inhibitor, I personally find that MAO B inhibitors only "work" short term and eventually I end up feeling worse.

[niner]

I think you folks are mis-reading the abstract. The researchers were comparing effects of three treatments. A statistically significant result would mean one or more of the treatments was more effective than the others (e.g., fluoxetine is more effective than curcumin, say). The non-significant result is the "news" - curcumin can't be distinguished from fluoxetine in terms of treatment effects.

OK, it looks like curcumin can't be distinguished from fluoxetine, but it still looks to me like none of them worked...

Curcumin, an active ingredient of Curcuma longa Linn (Zingiberaceae), has shown potential antidepressant-like activity in animal studies. The objectives of this trial were to compare the efficacy and safety of curcumin with fluoxetine in patients with major depressive disorder (MDD). Herein, 60 patients diagnosed with MDD were randomized in a 1:1:1 ratio for six weeks observer-masked treatment with fluoxetine (20 mg) and curcumin (1000 mg) individually or their combination. The primary efficacy variable was response rates according to Hamilton Depression Rating Scale, 17-item version (HAM-D17 ). The secondary efficacy variable was the mean change in HAM-D17 score after six weeks. We observed that curcumin was well tolerated by all the patients. The proportion of responders as measured by the HAM-D17 scale was higher in the combination group (77.8%) than in the fluoxetine (64.7%) and the curcumin (62.5%) groups; however, these data were not statistically significant (P = 0.58). Interestingly, the mean change in HAM-D17 score at the end of six weeks was comparable in all three groups (P = 0.77). This study provides first clinical evidence that curcumin may be used as an effective and safe modality for treatment in patients with MDD without concurrent suicidal ideation or other psychotic disorders.

It sounds like by "these data", they mean the effects of any of the three interventions on the HAM-D17. Did they mean that the difference in response rates was not significant? Maybe that's it, since a 62.5 to 77.8% response rate with n=20 must have been better than 0.58. There was no actual placebo used in this experiment. That would have been helpful, but may have been difficult to get past human subject review, since these patients were sick and there are treatments that are recognized to "work", however well or unwell that might be.

[Hebbeh]

Discussion in Ergo-log:

http://www.ergo-log....ozac-study.html

[blood]

... curcumin can't be distinguished from fluoxetine, but it still looks to me like none of them worked... There was no actual placebo used in this experiment. That would have been helpful, but may have been difficult to get past human subject review...

I suppose it is a reasonable design for a study that was probably run on a very small budget. The researchers side step the controversy over whether prozac is any better than placebo (probably not an issue they can settle), and they get to say, with a straight face, that curcumin is as effective as prozac.

If nothing else, the study provides some data that would hopefully make other researchers want to look at curcumin more closely as a possible treatment for depression.

Regarding prozac not being as effective as placebo, I came across this Time article when googling, and thought it was interesting:

... in 2008, when a review of the research found that the drugs were actually no more effective than sugar pills, except in cases of the most severe depression.

Last month, research published in the Archives of General Psychiatry sought to help explain the paradoxical findings on SSRIs and other new generation antidepressant drugs, the increasingly popular medications that are now used by more than 1 in 10 Americans over 12. Using a new statistical approach, researchers led by Dr. John Krystal at Yale University School of Medicine reanalyzed data from seven clinical trials involving 2,515 patients, whose results were used to win FDA approval for the SNRI (a drug that affects both serotonin and norepinephrine) duloxetine (Cymbalta).

Known as growth-mixture modeling, the statistical technique allowed the authors to track how individual patients improved or worsened over time in response to medication or a placebo. The researchers found that roughly three-quarters of patients did better on medication than on a placebo. “That’s much more than half and half. That’s quite favorable,” says Krystal.

However, Krystal adds, just under a quarter of patients did not respond well to drug treatment and in fact did worse on antidepressants than did patients who were given a placebo.

The benefit of growth-mixture modeling is that it reveals treatment trajectories of patients rather than looking at outcomes on average. When some patients get better while others get worse, the true impact of the drug may be “canceled out” in the data if they are considered only in the aggregate, obscuring both the drug’s harms and its benefits. That may help explain why some research finds that antidepressants work no better than a placebo.

“This has enormous implications for understanding the limits of the effectiveness of our current medications,” says Krystal. “These data really caution against the demonization of antidepressants as merely placebo, but they do raise a concern that some people are better off on placebo than on the antidepressant that they’re getting.”

Edited by blood, 27 August 2013 - 10:05 AM.

[blood]

Discussion in Ergo-log:

http://www.ergo-log....ozac-study.html

This is interesting:

People suffering from depression not only have reduced concentrations of serotonin and dopamine; their hippocampus also shrinks. The hippocampus is an organ in the brain that plays an important role in the storage and retrieval of information. If the hippocampus is not working so well we store information in a way that it acquires negative connotations and we retrieve it in a negatively coloured way too. Anti-depressants work by enlarging the hippocampus.

Curcumin has the same effect, according to animal studies. In 2007 researchers at the University of Florida published the results of an animal study in which doses of 10 and 20 mg curcumin per kg per day resulted in hippocampus growth by boosting the synthesis of the neural growth hormone BDNF. [Brain Res. 2007 Aug 8;1162:9-18.] Chinese researchers discovered that the increase in BDNF synthesis is the result of the enzyme extracellular signal-related kinase [ERK] being activated in brain cells. [Behav Brain Res. 2012 Nov 1;235(1):67-72.]

Maybe these patients weren't actually severely depressed?

The results actually seem too good to be true. Anti-depressants usually require a few weeks for effects to start showing, and if they work they tend only to slightly reduce feelings of depression. Anti-depressants enable patients to start functioning again so that they can embark on recovery. To actually cure severe depression in scores of people within six weeks, as seems to be the case in the figure above, is virtually impossible.

[nowayout]

Regarding prozac not being as effective as placebo, I came across this Time article when googling, and thought it was interesting:

... in 2008, when a review of the research found that the drugs were actually no more effective than sugar pills, except in cases of the most severe depression.

Last month, research published in the Archives of General Psychiatry sought to help explain the paradoxical findings on SSRIs and other new generation antidepressant drugs, the increasingly popular medications that are now used by more than 1 in 10 Americans over 12. Using a new statistical approach, researchers led by Dr. John Krystal at Yale University School of Medicine reanalyzed data from seven clinical trials involving 2,515 patients, whose results were used to win FDA approval for the SNRI (a drug that affects both serotonin and norepinephrine) duloxetine (Cymbalta).

Known as growth-mixture modeling, the statistical technique allowed the authors to track how individual patients improved or worsened over time in response to medication or a placebo. The researchers found that roughly three-quarters of patients did better on medication than on a placebo. “That’s much more than half and half. That’s quite favorable,” says Krystal.

However, Krystal adds, just under a quarter of patients did not respond well to drug treatment and in fact did worse on antidepressants than did patients who were given a placebo.

The benefit of growth-mixture modeling is that it reveals treatment trajectories of patients rather than looking at outcomes on average. When some patients get better while others get worse, the true impact of the drug may be “canceled out” in the data if they are considered only in the aggregate, obscuring both the drug’s harms and its benefits. That may help explain why some research finds that antidepressants work no better than a placebo.

“This has enormous implications for understanding the limits of the effectiveness of our current medications,” says Krystal. “These data really caution against the demonization of antidepressants as merely placebo, but they do raise a concern that some people are better off on placebo than on the antidepressant that they’re getting.”

Except this is nonsense - effectiveness studies are not designed in such a way that patients who respond negatively "cancel out" patients who respond positively, so I think someone there is talking out of their asses.

Edited by nowayout, 27 August 2013 - 10:48 AM.

[blood]

Except this is nonsense - effectiveness studies are not designed in such a way that patients who respond negatively "cancel out" patients who respond positively, so I think someone there is talking out of their asses.

Here is the full text of the study mentioned in the Time article. The interview by Time was with one of its authors, John Krystal.

http://archpsyc.jama...ticleid=1107437

This sounds reasonable to me:

Trajectory-based methods address limitations of other approaches of longitudinal analysis of heterogeneous samples. For example, end-point analyses with last observation carried forward are often used, despite serious problems with bias and loss of temporal information.¹⁰ Mixed-effects models¹¹ use all available data on patients, reduce bias, and improve signal detection over end-point analyses.^{10,12- 13}However, they assume the same mean trajectory over time for all patients within the same treatment group. Therefore, they do not account for the fact that treatment responders and nonresponders have distinct patterns of response. In contrast, trajectory-based models (also known as latent class models¹⁴and growth mixture models^{15- 17}) allow identification of distinct classes of developmental trajectories and assessment of the effect of treatments on trajectory membership. These methods have been applied to treatment research studies in the areas of alcoholism research^{18- 19} and depression.^{20- 22}

Regarding your earlier comment that fluoxetine has been shown to be about as effective as placebo for depression - as far as I can tell, the mixed/ problematic results were shown with patients with mild to moderate depression; for those with severe depression, prozac is superior to placebo. Prozac also appears better than placebo at preventing relapse of depression.

Edited by blood, 28 August 2013 - 01:04 AM.

[nupi]

“This has enormous implications for understanding the limits of the effectiveness of our current medications,” says Krystal. “These data really caution against the demonization of antidepressants as merely placebo, but they do raise a concern that some people are better off on placebo than on the antidepressant that they’re getting.”

Considering they used Duloxetine I am not surprised that people would get worse. Nasty stuff it is.

[blood]

Update
 
1) Curcumin better than placebo at ameliorating "major depression" (NEW STUDY)
 

J Affect Disord. 2014 Oct;167:368-75. doi: 10.1016/j.jad.2014.06.001. Epub 2014 Jun 11.

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

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 (500mg 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.

Copyright © 2014 Elsevier B.V. All rights reserved.

KEYWORDS:
Antidepressant; Clinical trial; Curcumin; Depression; Turmeric

2) Curcumin might augment the antidepressant effects of SSRIs/SNRIs (not established, needs further investigation)
 

Clin Neuropharmacol. 2013 May-Jun;36(3):73-7. doi: 10.1097/WNF.0b013e31828ef969.

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

Bergman J1, Miodownik C, Bersudsky Y, Sokolik S, Lerner PP, Kreinin A, Polakiewicz J, Lerner V.

Abstract

OBJECTIVES:
Depression is a widespread mental disorder in which nearly half of the affected people have recurrent symptoms. Drug combinations may produce cumulative adverse effects, especially in elderly and physically ill patients. It was demonstrated that curcumin possesses antidepressive activity in various animal models of depression, and a combination of curcumin with some antidepressants potentiates the antidepressive effect of these agents. We sought to evaluate the efficacy of curcumin as an antidepressive agent in a combination with other antidepressants in patients with major depression.

METHODS:
Forty patients with a first episode of depression participated in a 5-week, double-blind, randomized, placebo-controlled study. The subjects were treated with either 500-mg/d curcumin or placebo together with antidepressants (escitalopram or venlafaxine) during August 2010 until June 2011. The outcome measures were Clinical Global Impression-Severity Scale, Hamilton Depression Rating Scale, and Montgomery-Asberg Depression Rating Scale.

RESULTS:
Analysis of variance showed significant positive changes in both groups from baseline to the end of the study in all scales of measurement. These changes became significant from the first visit after 7 days of treatment. There was no difference between curcumin and placebo, which means negative results. However, the patients in the curcumin group demonstrated a trend to a more rapid relief of depressive symptoms in comparison to those in the placebo group. None of the patients complained of any adverse effect during the study.

CONCLUSIONS:
Although there is no definitive proof that curcumin can induce an earlier beneficial effect of antidepressive agents, it seems like an extended study is needed to prove it, using higher therapeutic doses of curcumin.

Edited by blood, 24 August 2014 - 09:27 AM.

[Area-1255]

And here:
http://www.longecity...-in-depression/

Turmeric acts as an MAO-inhibitor, and combined with piperine and black pepper - it will inhibit both MAO-A and MAO-B, producing significant anti-depressant and stimulant effects. Be careful about combining these with an SSRI antidepressant or 5-HTP - as the risk of developing serotonin syndrome (excess serotonin that can cause hypertensive crisis) nearly quadruples. 

Edited by Area-1255, 25 August 2014 - 11:31 PM.

[blood]

Interesting recent study - 1000mg curcuminoids + 10mg piperine enhances effectiveness of antidepressants in folks with major depression:
 

Phytother Res. 2014 Aug 4. doi: 10.1002/ptr.5211. [Epub ahead of print]

[url=http://www.ncbi.nlm.nih.gov/pubmed/25091591]Investigation of the Efficacy of Adjunctive Therapy with Bioavailability-Boosted Curcuminoids in Major Depressive Disorder.

Panahi Y1, Badeli R, Karami GR, Sahebkar A.

Abstract

Current medications have limited efficacy in controlling the symptoms of major depressive disorder (MDD), and are associated with several adverse events on long-term use. Curcuminoids are extremely safe and multifunctional phytopharmaceuticals that have been shown to alleviate depressive symptoms in a variety of experimental models. The present study aimed to investigate the efficacy of curcuminoids as an add-on to standard antidepressants in patients with MDD. One hundred and eleven subjects were assigned to standard antidepressive therapy plus curcuminoids-piperine combination (1000-10 mg/day; n = 61) or standard antidepressive therapy alone (n = 50) for a period of 6 weeks. Efficacy measures were changes in the psychological status on the basis of the Hospital Anxiety and Depression Scale (HADS) and Beck Depression Inventory II (BDI-II). The BDI-II and HADS total and subscale scores were reduced by the end of trial in both study groups. There were significantly greater reductions in total HADS score and subscales of anxiety and depression in the curcuminoids versus control group (p < 0.001). Likewise, reductions in BDI-II total score and scores of somatic and cognitive subscales were found to be greater in the curcuminoids compared with control group (p < 0.001). Co-administration of curcuminoids with piperine may be used as a safe and effective add-on to standard antidepressants in patients with MDD. Copyright © 2014 John Wiley & Sons, Ltd.

Copyright © 2014 John Wiley & Sons, Ltd.

KEYWORDS:
anxiety; clinical trial; curcumin; depression; piperine

Edited by blood, 27 August 2014 - 04:14 AM.