Wednesday, March 5, 2008

Behavioral Economics of Pain and SSRIs

More health economics in the popular press:

1) Check out this interesting article in the NYT about a study in which patients were given placebos for pain relief. A randomly selected group of these patients were told that the placebos were (relatively) costly while another group was told that these were cheap. Those in the former group were much more likely to report reduced pain post-treatment.

More behavioral economics: a recent New Yorker book review with a great introduction to the field. (Props to Jeremy and Maheer, respectively, for the links).

2) This week's Economist has a great article on the efficacy of selective serotinin reuptake inhibitors (SSRIs) in treating depression. Apparently, a meta-analysis in PLoS Medicine suggests that previous studies have overstated the SSRI treatment effect. The discrepancy appears to be due to the treatment of publication bias: whereas earlier analyses looked exclusively at published studies, this paper was careful to track down unpublished clinical trials, as well. (The Economist piece cites supporting evidence that selective publication is rampant in the anti-depressant literature. As you might guess from previous posts, I am not too surprised by this.)

However, as the article notes, all may not be lost for SSRIs: a year old National Bureau of Economic Research working paper finds large effects of anti-depressant use on reducing completed suicides. Using cross-country data, this study relies on an instrumental variable strategy where sales of other drugs are used as IVs for SSRI sales conditional on a variety of observable socioeconomic characteristics, and country and time fixed effects. The argument is that, conditional on observables, the IV is uncorrelated with population mental health and other unmeasurable that determine the suicide rate. I'm a bit skeptical, but the authors do a decent job presenting various robustness and falsification tests.

A few questions that come to mind:

1) Is it possible that both conclusions on SSRIs to be correct? That SSRIs might be not be helpful in treating depression but may be prevent depressed people from taking their own lives? If you have some thoughts on this, please comment. I'm extremely curious.

2) Why don't more meta-analyses make the attempt to gather unpublished study results? According to the Economist piece, unpublished results are required to be submitted to the FDA by law. So the data is out there and (obviously) not impossible to retrieve.

3 comments:

Anonymous said...

You raise valid points regarding the use of SSRIs for combating depression and suicide, and the related research. In theory, meta-analyses should always include unpublished data because of bias towards publishing positive results. Unlike basic laboratory research, all clinical human subject research is required to register on a public government website before enrollment of the first patient. This provides a venue for patients to locate ongoing studies, which they may be interested in joining. In addition, it provides transparency in the field. By doing so, a study sponsor cannot mention positive results without also mentioning negative results. The unfortunate flipside to this is that regulations for publishing all results (positive and negative) do not exist for other research designs. Health research that does not use human subjects is not required to publish negative results, thereby leading to the strong publication bias. In addition, we are not contributing to the advancement of knowledge if negative results aren’t published. Bottom line is: It sucks.
As for the use of SSRI’s: I apologize in advance if I am being presumptuous in regards to your sentiments on prescribing anti-depressants. And i admittedly did not take the time to thoroughly read all the articles you have linked. However, I agree with the statement made by Dr. Nutt as to the usefulness of anti-depressants versus traditional counseling. I also understand and acknowledge that there may be a very strong placebo effect. However, until you have experienced a depressive episode and the toll it takes on your quality of life, I don’t know that we can say whether the placebo effect is bad. Who cares if it’s really the drugs or psychosomatic? If it brings a person out of the depression faster than the natural course, then I think it is worth it. Yes, it’s wrong for research to “claim” the effect of the drugs is stronger than it truly is, and maybe the typical prescribing practices should be re-evaluated but I don’t see the problem in assisting people in every way possible when depression severely decreases the quality and productivity of their lives.

Atheendar said...

Thank you for this really thoughtful comment. I completely agree with you on all accounts, especially on the one that espouses a multi-faceted approach towards dealing with depression, a disease which has large personal, external and economic consequences.

You bring up a great point about the potential utility of placebo effects. It's definitely worth our understanding more about how these work and what we can take from this towards more informed treatment regimens. Do you know of any research that gets at this?

Finally, just to clarify, even if SSRIs have no tangible effect on clinical depression (placebo or otherwise), the effect on suicides (which is extremely large if you believe the linked paper), in my opinion, justifies the continued use of these agents in clinical settings.

I think this is the start of a long debate on the efficacy SSRIs, and I look forward to additional evidence on their effectiveness as time goes on.

Thanks again for the thoughtful comment. It's great to start discussions on important topics as these.

Anonymous said...

I do not know of any research that has investigated a means to tailor treatment for depression. Generally, it may be a stepwise plan that starts with non-pharma treatment like cognitive behavior therapy. If an individual reaches a point at which he/she feels talk therapy is insufficient or the patient and their therapist feel progression is not being made, a pharmaceutical evaluation may be the next step. However, it's an intriguing thought - to research the traits of individuals and to which treatments they respond best. Clearly, it is unethical to test placebos as an "active treatment" for people suffering from depression. But in reality, it may be all a certain type of person needs to bring them out of a depressive episode.