Harvard department inspires him to create much higher-quality research. 19 placebo-controlled drug trials that suggested that almost all of the benefits of you matter more than you think pdf were due to the placebo effect.
Psychiatrists denounced him, saying that you can choose pretty much whatever studies you want for a meta-analysis. FDA’s data through the Freedom of Information Act. Since drug companies are required to report all their studies to the FDA, this theoretically provides a rare and wonderful publication-bias-free data set. This launched a minor war between supporters and detractors. The magnitude of benefit of antidepressant medication compared with placebo increases with severity of depression symptoms and may be minimal or nonexistent, on average, in patients with mild or moderate symptoms.
For patients with very severe depression, the benefit of medications over placebo is substantial. Of course, a very large number of antidepressants are given to people with mild or moderate depression. I don’t think anyone is arguing against the proposition that there was an embarrassing amount of hype that has now been backed away from. Most studies find SSRI antidepressants to be no more effective in treating depression than older tricyclic and MAOI antidepressants. Most studies aren’t really powered to do this.
It seems clear that there aren’t spectacular differences, and hunting for small differences has proven very hard. If you’re a geek about these sorts of things, you know that a few studies have found non-significant advantages for Prozac and Paxil over older drugs like clomipramine, and marginally-significant advantages for Effexor over SSRIs. But conventional wisdom is that tricyclics can be even more powerful than SSRIs for certain very severe hospitalized depression cases, and a lot of people think MAOIs worked better than anything out there today. But none of this is very important because the real reason SSRIs are so popular is the side effect profile. Tricyclics had a bad habit of causing fatal arrythmias when taken at high doses. This is really really bad in depression, because depressed people tend to attempt suicide and the most popular method of suicide attempt is overdosing on your pills. So if you give depressed people a pill that is highly fatal in overdose, you’re basically enabling suicidality.
This alone made the risk-benefit calculation for tricyclics unattractive in a lot of cases. Add in dry mouth, constipation, urinary problems, cognitive impairment, blurry vision, and the occasional tendency to cause heart arrythmias even when taken correctly, and you have a drug you’re not going to give people who just say they’re feeling a little down. MAOIs have their own problems. There are some MAOIs that get around these restrictions in various clever ways, but they tend to be less effective. SSRIs were the first class of antidepressants that mostly avoided these problems and so were pretty well-placed to launch a prescribing explosion even apart from being pushed by Big Pharma. People became more aware of publication bias a couple of years after serious research into antidepressants started, and it’s not surprising that these were a prime target.
When this issue rose to scientific consciousness, several researchers tried to avoid the publication bias problem by using only FDA studies of antidepressants. The FDA mandates that its studies be pre-registered and the results reported no matter what they are. The results haven’t been good. Recent reports suggest that efficacy of antidepressant medications versus placebo may be overstated, due to publication bias and less efficacy for mildly depressed patients. FDA registered studies were positive. 1 of the 38 were published.
I think a lot of this has since been taken on board, and most of the rest of the research I’ll be talking about uses FDA data rather than published data. As mentioned above, when you try to control for publication bias, the effect size of antidepressant over placebo is 0. This number can actually be broken down further. 92 and the effect size of antidepressants is 1.