There's been a lot of talk recently about how antidepressants are not particularly effective. Either most people don't respond, or when they DO respond, it's placebo, or the side effects are too much. None of this is wrong, though I personally do not think the current antidepressants are quite as bleak as recent coverage is implying.

What is certain is that there are people who will respond to the current antidepressants on the market, and people who will not. The question then becomes: what are the differences between these two groups of people? What makes the difference between a "responder" and a "non-responder"? And how can we determine that in order to make treatment more efficient for those who are "responders" and search for alternatives for those who are not?

This latest paper suggests that we might have an indicator in humans: BDNF.

Wolkowitz et al. "Serum BDNF levels before treatment predict SSRI response in depression" Progress in Neuro-Psychopharmacology & Biological Psychiatry, 2011

BDNF stands for brain derived neurotrophic factor, a growth factor that many people believe plays a role in antidepressant response. The idea stems from the hypothesis that symptoms of major depression are caused by decreases in the birth of new neurons in your brain. Long term administration of antidepressants can increase the birth of new neurons in the brain, and this is thought to help depressive symptoms. One of the ways that antidepressants are thought to work to increase cell proliferation in the brain is via increasing BDNF.

Most of the studies on BDNF and antidepressants have been done in animal models, but BDNF is detectable in humans in the blood. It is low in patients who are depressed, and can be increased by antidepressants. But could BDNF levels also help us PREDICT who could respond to antidepressants and who won't?

To find this out, the authors took a bunch of untreated patients who had been diagnosed with depression, and a bunch of controls. They took blood levels of BDNF, and then treated the depressed patients with antidepressants (either escitalopram or sertraline). They then took their BDNF levels again.

Overall, you can see that the depressed patients ("MDD Baseline") had lower BDNF levels than controls, and that antidepressant treatment increased their BDNF levels ("MDD End"). But then, they took apart the depressed patients, and correlated their BDNF levels at the BEGINNING (before treatment) with their depression levels at the end of treatment.

What you can see here is a correlation between the BDNF levels and a change in depression score. It turns out that those patients with the highest levels of BDNF to begin with, had the best improvements in depression score when treated with antidepressants.

And you can see here that baseline BDNF levels could predict who was a responder to the treatment and who was not. What's particularly interesting is that the baseline BDNF levels were not correlated with the original depression score (they did not predict how depressed the patients were), they only correlated with the improvement during treatment.

The question now is WHY. It could be that having a higher baseline BDNF allows for more plasticity in neuron birth when patients are treated with antidepressants. It's possible that people with higher BDNF levels are near a natural remission anyway. It's possible that BDNF and antidepressants could work together, making higher BDNF levels important to the success of the drug. We don't know any of this yet, all we know right now is that there is a correlation between antidepressant success and original BDNF levels.

Of course this is a preliminary study. It was a small sample size for humans (only 30 patients), and needs to be replicated. but the correlation is interesting, and with more studies to back it up, could be used to determine who will respond to first line treatments and who will not, as well as allowing us to study the non-responders, and find new drugs for them as well.

Wolkowitz, O., Wolf, J., Shelly, W., Rosser, R., Burke, H., Lerner, G., Reus, V., Nelson, J., Epel, E., & Mellon, S. (2011). Serum BDNF levels before treatment predict SSRI response in depression Progress in Neuro-Psychopharmacology and Biological Psychiatry, 35 (7), 1623-1630 DOI: 10.1016/j.pnpbp.2011.06.013