Thursday, April 19, 2012

Is Depression An Inflammatory Disease?

This past weekend, I had the opportunity to hear Dr Andrew Weil speak at a conference put on by the University of Maryland’s Center for Integrative Medicine. Dr Weil deserves a lot of credit for recognizing the importance of mind-body medicine and nutrition at a time (the early 70’s) when it was almost entirely unheard of, and when the naturopathic profession was only beginning to wake out of several decades of slumber. Additionally, he’s become a focal point that has helped to bring shape to a diverse group of healthcare practitioners who would otherwise be practicing in isolation. His role in encouraging the evolution of medicine would be hard to understate.

Towards the end of his talk, Dr Weil discussed the possibility that the root cause of depression might not be, as is often suspected, a serotonin imbalance (for which the ‘solutions’ are Paxil, Prozac, Zoloft, etc), but rather an inflammatory process. In the discussion, he mentioned a study in which NSAIDs (non-steroidal anti-inflammatory drugs, such as aspirin or ibuprofen) showed the same effect as traditional anti-depressants, and that, by extension, turmeric or ginger might be effective anti-depressants. Fascinating stuff, right? Needless to say, I was intrigued, and spent much of the next day trying to pull articles.

After a few hours, I found that Dr Weil had probably overstated things a bit in his presentation. There IS increasing evidence that some forms of depression are linked to inflammatory disease markers, but there AREN’T many studies that have looked at the therapeutic value of anti-inflammatories on depression.

So, here’s what I was able to find. Many inflammatory cytokines (chemical messengers) have been documented to be elevated among depressed people, including several interleukins, and it appears that many pro-inflammatory enzymes are up-regulated in patients suffering from major depression (1, 2, 3, 4, 5, 6). Interestingly, some of the body's compensatory anti-inflammatory markers are similarly elevated. This body of evidence is growing steadily, and while there is some variability in which biomarkers are elevated, there is consistent evidence that certain pro-inflammatory cytokines are elevated in patients with depressive symptoms.

These observations have lead to the publication of many articles that suggest that researchers investigate the use of anti-inflammatories in the treatment of depression. Indeed, the number of articles I was able to find advocating for research into this as a potential treatment for depression far exceeds the number of articles I was able to find which either document the effects of inflammatory cytokines on depression or the effects of anti-inflammatory drugs on depression. I found a number of such articles, from researchers all over the US and all over the world, but I’m only going to provide links to a few of them, because many essentially say the same thing and draw on the same sources (1, 2, 3). Researchers are writing about their interest in this potential treatment, but few are actually researching the use of anti-inflammatories as part of treatment.

What few clinical trials I was able to find mainly focus on the use of celecoxib (Celebrex) as an adjunct treatment in depression. Two articles I found supported the hypothesis that the combination of celecoxib and an antidepressant provided greater relief from depression than an anti-depressant alone (1, 2). An additional trial found that celecoxib provided significant relief from depressive episodes as an adjunct treatment in bipolar disorder. These were all fairly small trials, but they certainly make us think, and as a naturopathic physician, I find this information extremely useful – celecoxib is nothing special, pharmacologically speaking, and it’s action can easily be performed by a natural substance, such as turmeric or ginger.

However, the largest study I was able to find found no benefit. It was a re-evaluation of data from a study investigating the use of anti-inflammatory drugs to prevent Alzheimer’s progression, and among the 500 participants who also had major depressive symptoms, no relief was gained from either celecoxib or naproxen. While the study methods weren’t ideal, it’s still an important piece of information. The take-home message from these studies, I believe, is that anti-inflammatories may have a beneficial effect on depression in conjunction with an anti-depressant.

At the end of the day, though, what this whole line of thinking actually indicates is that we really have very little understanding of depression. On an individual level, practitioners can help people quite a lot with depression, but it takes time and work, and above all, a deep understanding of what is causing that person to be depressed. However, on a large scale, we don’t understand depression – we don’t understand why so many people are depressed, we don’t understand what’s making them depressed, and we don’t understand how to fix them. Again, I underline that this is on a large scale – on an individual scale, we can change lives, because depression is individual in its origin and similarly unique in its resolution. It’s a result of a combination of biochemical, environmental, and social factors, and treatment must take into account all of these factors.

I think the reason we don’t understand depression on a large scale is that, in some ways, there is no such disease as depression. A disease has a clear etiology or can be diagnosed using a specific marker – iron-deficiency anemia, lupus, strep throat, etc are examples of diseases. ‘Depression’, as we call it, is many, many diseases all masquerading around with the same major symptom. These dis-eases arise from a variety of causes, and vary significantly between patients. Though a variety of practitioners can help work through depression, including MDs, psychologists, and therapists, I believe that the individualized treatment that is a hallmark of naturopathic medicine offers the personalized approach necessitated in depression.