Map of life expectancy at birth from Global Education Project.

Thursday, July 21, 2005

Telling Prozac to shut up

Okay, now that we've gotten that statistical significance thing in our tool kits, let's put it to work. I haven't managed to stimulate a whole lot of cries of outrage here, but I did once manage to get a rise out of somebody by saying that antidepressants don't work. How can that be? There are millions of depressed people who have taken antidepressants and gotten better.

Yes there are, but it turns out that people with depression also get better if you give them gel caps filled with kitty litter. In other words, there is a very strong response to placebos in depression. So the question is not actually whether antidpressants work, it's whether they work any better than burying a clove of garlic in the back yard under a full moon and then swinging a dead cat around your head three times.

The first question is, "What do you mean by 'better'?" The usual definition is a better (lower) score on somethign called the Hamilton Rating Scale for Depression. This has various items, some of which score from 0 to 2, others up to 4. The most popular 17 item version can score up to a total of 52. In some clinical trials, but not all, people improved more on one or another antidepressant than they did on placebo.

Joanna Moncrieff and Irving Kirsch, in the latest British Medical Journal, address the efficacy of antidpressants in adults. They tell us that, "Although the [National Institute for Health and Clinical Excellence]NICE meta-analysis of placebo controlled trials of Selective Serotonin Reuptake Inhibitors found significant differences in levels of symptoms, these were so small that the effects were deemed unlikely to be clinically important." So why are SSRIs supposedly so effective? Because changes in the Hamilton score are arbitrarily divided into a range considered to constitute remission, and non-remission. If we consider, for example, that a 12 point improvement is the cutoff for "success," then a patient with 11 point improvement is a therapeutic failure, while a patient who does one point better is a success.

Let's say that 50% of the people on placebo get to 12 points or better improvement, and 65% of people on SSRIs do. Then one might conclude that 15% of the people are actually benefiting from SSRIs, which is about the average finding. (I'll bet you thought it was much better than that!) Even that conclusion is largely arbitrary. And the real difference in average response between SSRIs and placebo is too small to matter.

But wait! The Hamilton Depression Scale has several questions about sleep and anxiety, so any sedative will produce improvement, even if it doesn't do anything for depression. There are other methodological problems with antidepressant trials. For one thing, antidepressants have noticeable side effects, so people in the "intervention" arm -- the people actually taking the drug -- know something is happening, while the people on placebo don't feel anything. This presumably amplifies the placebo effect, but it might do just as much good to give people something that just made them feel a little bit nauseous or light headed.

Finally, long-term results for people given antidepressants are not encouraging. Most people continue to have bouts of depression. Indeed, the only relevant study shows that people with depression who were prescribed antidepressants had worse long-term outcomes than people who weren't given them!

Bottom line? These researchers are convinced that SSRIs are worthless. And so am I.