Antidepressants...

For me, one of the most distressing trends in psychiatry is the huge upswell of proscribing anti-psychotic medication for depression. There is an interesting back and forth going on over at Psychology Today about aspects of this issue. For instance this, from an interview with David Healy:

Interviewer: Between 1996-2001, you explain, there was a fivefold increase in the use of antipsychotics (Zyprexa, Risperdal, Abilify, Seroquel, and others) in preschoolers and preteens...how much of that shift is attributable to SSRI antidepressants coming off patent while the antipsychotics were still major revenue earners?


Healy: I think this was in fact central to what happened. The antidepressants were due to come off patent whereas the anticonvulsants were older drugs that could be repatented for this purpose, and the antipsychotics—which also could be (and were) marketed as mood stabilizers—were early in their patent life.

A related point that’s worth bringing out is that the switch happened because companies weren't able to make new and more effective antidepressants. Had they been able to do so, I think they would have probably stuck with the depression model rather than made the switch to bipolar disorder.

In terms of what is happening in the US, I think we have to look at how skillfully the drug companies have exploited doctors. Doctors have wanted to help. While the drugs are available on prescription only, doctors tend to see giving a medicine as the way to go, where previously they had been much more skeptical about the benefits of drug treatments.

The drug companies have engineered a situation in which academics have become the primary spokespeople for the drugs. We see the sales rep in the corner and think we can easily resist his or her charms—but we still let them pick up the drinks tab. But it's the academics who sell the drugs. Doctors who think they are uninfluenced by company marketing listen to the voices of academic psychiatrists when these, in the case of the antidepressants or antipsychotics given to children, have talked about the data from controlled trials, and by doing so have been witting or unwitting mouthpieces for company marketing departments.

Where Healy asserts that "biomythology" is at work- essentially a complex of myths and pseudo-science regarding how the brain works and the efficacy of certain psychiatric drugs- and that, as in the above passage, it redounds to the profit of big pharma. Nasser Gaemi objects, and makes some fair points, and notes some substanial research. He does avoid a big question, in that it seems that he quibbles on some fine points but does not contend with the large scale manipulation of data that Pharma engages in.

Gaemi takes a more comprehensive approach in looking at the rates of relief associated with anti-depressant use. There are few significant differences, and none work particularily well:

1. Of 117 studies included in the meta-analysis, only 15 were unpublished studies obtained from the pharmaceutical industry. Another study found that about half of the antidepressant clinical trials are negative but unpublished, while about 90% of the published literature is positive. Massive unpublished negative study bias goes on; extrapolating from that study, we would expect that this study, which only consists of about 10% unpublished (and presumably mostly negative) data, overestimates benefits with study drugs versus other drugs by some percentage; perhaps there are up to 30-50% more studies out there not included in this review.

2. The benefits seen were small in effect, with about 30 to 50% relative benefits of one drug over another, where those benefits were seen. This is generally seen as a mild clinical effect; for comparison, smoking causes lung cancer by a relative risk of 1000%; that is considered a very large clinical effect. A doubling of benefit would be a 100% relative difference, tripling would be 200% (no difference is 0%). So a 30-50% difference, if real, is small.

If observation 2 is corrected for observation 1 above, that is, if we correct a small clinical benefit for an at least small probable overestimation of benefit (due to noninclusion of negative unpublished studies), then things are back to neck and neck again.

A couple of things come to mind. First, it seems that clinicians are turning to using anti-psychotics to treat depression for a couple of reasons: anti-depressants do not work very well and the Big Pharma companies are pushing them hard for their own reasons.

Second, people with mild depression do experience some relief with anti-depressants. I think this relief gets overgeneralized. Mild depression gets diagnosed, pathologized if you will, more often these days. I think this inflates the apparent efficacy of anti-depressants. Moreover, most clinicians really want to help and are helpless in the face of profound suffering. Simple solutions, or least a juggling of various simple solutions, is tempting.

Placebos work well. Mindfulness training works well. Hypnotherapy works well. Exercise and dietary changes work well. Cognitive therapy works well.

Sometimes nothing works. That's how it is sometimes.