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Can You Spice Up Your Antidepressant?

The evidence for curcumin in depression.

Wikimedia Commons
Source: Wikimedia Commons

Herbs, spices, vegetables and fruits are sources of many phytochemicals that have antioxidant benefits and reduce inflammation. How exactly phytochemicals work and how much might be optimal for health is a continuing question…and typical randomized trial results of any particular chemical tends to be underwhelming. Think blueberry or red wine extracts and all the promises of reversing aging...purified chemicals don't seem to have much of an advantage of whole foods when it comes to phytochemicals. However, over the years I’ve been asked many times to comment on the specific plant compound curcumin, found in the spice turmeric. I held off, mostly because there wasn’t much data for psychiatry. Curcumin isn’t well absorbed into the central nervous system as it is mostly protein-bound in the periphery, so it’s easy to be skeptical. But let’s examine the slow pile-up of studies that have now accumulated and see if they support curcumin’s use in the treatment of depression.

So what is curcumin? It’s the active ingredient in turmeric making up about 2-5% of that spice. Of interest to medicine, it has multiple anti-inflammatory effects. It seems to lower oxidative stress, acts as an inhibitor of the pro-inflammatory cascade, and in animal studies seems to provide benefit or neurons, regulate the stressed out hypothalamic-pituitary-adrenal axis that becomes disabled in depression and anxiety, and influence serotonin and dopamine activity. But it if it’s not really absorbed into the central nervous system, how could it help depression? Well, since depression is a disease of both central nervous system and systemic inflammation, and since systemic bodily stress affects the hypothalamic-pituitary-adrenal axis in a way that can increase risk of depression, any systemic anti-inflammatory agent might have some antidepressant benefit. This mechanism is similar to why some scientists think probiotics might be beneficial for depression or anxiety.

It should be noted that studies of potent anti-inflammatories such as NSAIDs have been mixed when it comes to demonstrating much benefit compared to risk for depression, but then NSAIDs have many documented serious adverse side effects, so any modest improvement is offset by these real dangers. The hope is that systemic anti-inflammatories like probiotics or phytochemicals might give us modest but helpful improvements without the high cost of something like NSAIDs.

Curcumin is more interesting than many other alternative-medicine highly-touted phytochemical compounds as an anti-inflammatory because there’s already about a decade of human data for adjunctive and/or remission stability improvement from curcumin in autoimmune diseases such as ulcerative colitis. These studies show some benefit and very few side effects at fairly high doses, double or quadruple those used in the depression studies.

In depression trials, 500mg or 1 gram of curcumin daily (divided dose) was used in various protocols against placebo or even a combination with saffron. A pilot trial in 2013 showed no benefit, but the dose was quite low and the trial, at 5 weeks, was short compared to most antidepressant trials. Later trials with higher or combination doses that lasted 8-12 weeks did show at least some separation from placebo between 4-8 weeks, and there were some interesting effects on inflammatory biomarkers. Inflammatory markers associated with depression such as TNFalpha, interleukin 1B, and C reactive protein are lowered with the administration of curcumin. The last combination curcumin/saffron trial showed insignificant separation of curcumin from placebo overall, but the atypical depression subset (folks with symptoms such as increased sleepiness, weight gain, and lack of energy) did have significant benefit. There are a lot of questions about what, exactly, “atypical” depression represents, but one theory is that the atypical subset is highly related to systemic inflammation and a chronic overactive inflammatory response, similar to metabolic syndrome (which is a combination of weight gain, insulin resistance, high triglycerides, and high blood pressure usually associated with a high C-reactive protein and other measures of systemic inflammation).

In all of the controlled trials, curcumin side effects were similar to placebo, with the most common complaint being digestive (bloating or diarrhea). We must also note that in many of these trials, curcumin was used in combination with standard medicine or psychotherapy, not in isolation.

My take on the data to date…well, it’s not time to add curcumin to the water supply. However, there appears to be few side effects and it seems to be helpful, at least for the short term. I’m far more likely to recommend a whole foods diet with lots of fruits, vegetables, and spices as adjunct to standard care than any particular supplement without some other compelling reason, but for someone who has atypical depression, very low motivation or energy, who can’t quite manage a good diet yet, curcumin might be a stepping stone in addition to standard care to feeling good enough to engage in better self care. 500mg twice a day seems more effective than lower doses, and four to eight weeks was needed to show any benefit. I would like to see longer, larger studies and also to see if there is any emergence of insomnia, irritability, or mania in these larger studies. Longer term use might also be helpful for long term inflammatory brain processes such as dementia…so it would be very interesting to see more work done in the area of mild cognitive impairment or seeing if there is less dementia in those using curcumin chronically over many years for other conditions.

One last caveat…it’s important to do some research when it comes to buying brands of spices and herbs for chronic daily medicinal use. Many brands simply don’t contain what is on the label, or may be contaminated with gluten or heavy metals. Consumer reports and organizations like US Pharmacopeia help work with industry to independently test brands to see if what you buy is what you get. Look for USP certified brands and search the websites of your supplement companies to see if they allow for verified outside independent testing of their products.

Source: wikipedia

Copyright Emily Deans MD

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