A new meta-analysis of research on modern antidepressants -- some of it unpublished by the drug companies -- suggests that the drugs have little advantage over placebos.
Why then do so many people consider drugs like Prozac to be miracle drugs for depression -- many putting up with serious sexual side effects in order to take them? Are they simply being duped by a placebo effect or avoiding withdrawal symptoms? And how could drugs which are little different from placebo also produce suicidal or even homicidal thoughts in some patients?
The answer reveals a key flaw of randomized clinical trials and meta-analyses: when you are looking at aggregated data, huge individual differences can be washed out. For example, let's imagine a drug that causes people with one genetic variation to have a profound positive effect -- but causes those with another to get dramatically worse and has little effect on everyone else.
A clinical trial could easily find that this drug has no advantage over placebo, depending on the proportion of people with each gene in the study. Another study of the same drug might find it to be a blockbuster -- while another found it dangerous. Same drug, different populations.
Indeed, researchers looking at antidepressants find exactly these results, according to researcher David Healy, whom I interviewed a while back for Reason. Healy is not known as a drug company booster -- his most recent book is titled Let Them Eat Prozac: The Unhealthy Relationship Between the Pharmaceutical Industry and Depression. It is widely believed he was not hired at one academic job because of his strong views on these medications.
But he continues to prescribe them because the right drug in the right person can be lifesaving.
Some people are strong responders to one drug -- but give them another in the same class, and they become actively suicidal. Most people have a slight positive effect; some have a slight negative effect. In aggregate, a drug that is a home run for one person and potentially fatal to another looks inert.
This doesn't mean that we don't need randomized clinical trials or meta-analyses: RCT's are the gold standard of evidence-based medicine with good reason. But it does mean that until we can better understand how genetic variation affects drug response, we will continue to have these boring debates about Prozac: Angel or Devil.
Especially in a context where the media often refuse to explain how ideological biases affect people's positions on these medications and conveys the story as a clash between two conflicting views of the world. Both sides are right -- but only about the response of particular people to particular drugs. This is why it can be true both that 80% of depressed people can find a medication that works and that clinical trials don't find these drugs much better than placebo when looking at the general population of depressed people.
Cross-posted from Scientific American's 60 Second Science
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