There are more than two dozen FDA-approved antidepressants out there. How can you determine which one is the best for you? This is the question posed by Steve Blatt MD in an article in Psychiatric Times, a publication of the American Psychiatric Association.
Dr Blatt’s short answer: We have no idea. Finding the right antidepressant is a crap-shoot.
His long answer has to do with the fact that untold clinical efficacy trials and real world effectiveness trials, not to mention a host of meta-analyses that pool these trial results, have failed to separate one antidepressant - much less a class of antidepressants, much less a combination of antidepressants - from the rest of the pack.
In clinical trials involving a placebo, this translates roughly into fifty percent of the patients on the test drug getting at least fifty percent better. For trials comparing one test drug against another, the numbers are higher. This is possibly because, with no placebo in the mix, patients have a higher expectation of their pill working.
I recall attending my first American Psychiatric Association meeting in 2002, in Philadelphia. On a monitor in the lobby, an ad for Effexor showed a man in a sweatsuit running up the steps of the local art museum and lifting his arms, Rocky-style.
Wyeth, the makers of Effexor, had recently conducted a meta-analysis that showed a higher remission rate for their drug compared to other antidepressants. At the conference, the researchers who conducted the analysis were talking up the results.
On the basis of those results, Wyeth’s marketing team had entered into a full-court press. Among other things, this involved paying psychiatrists very good money to give talks mainly to primary care physicians. One of these psychiatrists was Daniel Carlat, who described his adventures as Dr Drug Rep in a 2007 feature article in the NY Times Magazine.
Dr Carlat, who is an associate professor at Tufts, kept up with the literature, and what he later found unsettled him. Subsequent studies failed to reproduce the results of the original study. Researchers were poking holes in the methodology of that study. Moreover, there were safety issues involving Effexor.
Dr Carlat wound up giving a talk that strayed from the strict drug company party line. Wyeth let him go.
In a piece last year on Health Central, I noted that none of the three evidence-based major depression treatment guidelines I surveyed singled out one antidepressant as being more effective than the others. One of these guidelines, issued by an agency of the British public health system, recommended a generic SSRI as a first option, on the basis of cost.
In other words, with all antidepressants offering pretty much the same probability of delivering the same result, you pick the one that will save the taxpayer the most money. In the US, with the insurance companies calling the shots, the issue of cost is also the paramount concern.
This does not mean all antidepressants are the same. Even drugs in the same class can produce very different results, based on the individual taking the drug. In theory, if we could match the right antidepressant to the right patient, we would produce much happier outcomes.
The catch, as Dr Blatt points out in his article, is we lack the means to do this. Gene-typing, for instance, holds out the hope of predicting in advance which patient will respond best to which antidepressant. Unfortunately, the sheer complexity of the human genome has frustrated the search for easy answers.
The other obvious route - testing patients for how they metabolize drugs - has similarly failed to yield answers.
In the meantime, we barely know what we’re treating. This is an issue I keep coming back to again and again, here on Health Central. At best, “depression” is an umbrella term that embraces any number of conceivable things that can go wrong in the brain. If our doctors have no idea why my condition may be biologically different from yours, how can they possibly prescribe the right drug?
Medicine, like most of science, is a game of probabilities, of “if-then” propositions. In other words, if we initiate A under B conditions, we have an X chance of producing C. In certain fields of medicine, the probabilities stack up convincingly well. In psychiatry, we can at least make a case that antidepressants in general offer a reasonable probability of improvement.
But which one? Which antidepressant? Alas, it’s a crap-shoot.
Advisory: The American Psychiatric Association Depression Treatment Guidelines warns that doctors should only treat a patient with an antidepressant after ruling out the possibility of bipolar. Unfortunately, general practitioners hand out these meds like candy, with no evaluation. Please - only use antidepressants under the care of a doctor who knows what she is doing and who regularly monitors your condition.
Published On: July 28, 2014