A RCT of the Tumor Necrosis Factor Antagonist Infliximab for Treatment-Resistant Depression

[Woolie]

Full title:
A Randomized Controlled Trial of the Tumor Necrosis Factor Antagonist Infliximab for Treatment-Resistant Depression

Authors: Raison et al
Date: 2012
link to article
Five minute video explanation for dummies

Not brand new research or anything, but kind of interesting - and relevant!

These researchers took a group of people diagnosed with treatment-resistant depression and treated them with infliximab or placebo. Infliximab is a drug that blocks tumour necrosis factor, a pro-inflammatory cytokine.

The study found no overall beenfit of treatment for the group as a whole. But for that subgroup of participants who had high(ish) C-reactive protein levels (indicating inflammation), treatment led to improvements on a self-report measure of depression.

But don't go away thinking that (some) depression is caused by inflammation, nor the other way around. When you look closer at the results, it appears that a lot of the "responders" were probably not depressed according to the strict meaning of the term, but rather had impaired physical functioning more generally - most probably including fatigue. Most of the "improvement" on the depression measure was people reporting that they could do more work and other activities following the treatment.

My conclusion:

* Infliximab reduces overall markers of inflammation (include CRP and TNF)

* People with high(ish) levels of inflammation benefit from infliximab

* The only thing the article probably has to say about actual depression (the concept) is that our diagnostic criteria are most likely too broad, and many physically ill people get caught in the net.

 

[Woolie]

PS Its kind of a big deal, because this study has created a whole industry of researchers claiming that when people feel sad, bad or stressed about the world they produce inflammation. You end up with really highly cited studies like this one:

experiences of social threat and adversity up-regulate components of the immune system involved in inflammation. The key mediators of this response, called proinflammatory cytokines, can in turn elicit profound changes in behavior, which include the initiation of depressive symptoms such as sad mood, anhedonia, fatigue, psychomotor retardation, and social-behavioral withdrawal. This highly conserved biological response to adversity is critical for survival during times of actual physical threat or injury. However, this response can also be activated by modern-day social, symbolic, or imagined threats, leading to an increasingly proinflammatory phenotype that may be a key phenomenon driving depression pathogenesis and recurrence, as well as the overlap of depression with several somatic conditions including asthma, rheumatoid arthritis, chronic pain, metabolic syndrome, cardiovascular disease, obesity, and neurodegeneration.

full article here

Now here's the problem for us: inflammation is most probably a huge factor in MECFS. In the past, we might have hoped that studies demonstrating elevated inflammatory markers in CFS would have helped show this is a real disease. But now you can see, even inflammation is being psychologised of late. I predict that the psychosocial CFS researchers will make the transition to inflammation research quite seamlessly - and still be able to claim it can all be fixed with therapy!

Sorry to put such a downer on everyone. But its worth knowing what researchers are really thinking when they talk about "inflammation" in MECFS.