There's a section in the article about a classic correlation vs. causation mistake: Early researchers noticed that drugs like Zoloft increased levels of seratonin in the brain, so it was assumed that depression is caused by low seratonin levels, but this is a big leap and new research suggests we were totally wrong:
As Carlat puts it, “By this same logic one could argue that the cause of all pain conditions is a deficiency of opiates, since narcotic pain medications activate opiate receptors in the brain.” Or similarly, one could argue that fevers are caused by too little aspirin.What's really scary is not the fact that antidepressants work only marginally better than placebos (which I've been hearing on and off for years), but the general corruption of drug companies:
If two trials show that the drug is more effective than a placebo, the drug is generally approved. But companies may sponsor as many trials as they like, most of which could be negative—that is, fail to show effectiveness. All they need is two positive ones. (The results of trials of the same drug can differ for many reasons, including the way the trial is designed and conducted, its size, and the types of patients studied.)Scarier yet is the fact that antidepressants can have lasting effects on the brain:
For obvious reasons, drug companies make very sure that their positive studies are published in medical journals and doctors know about them, while the negative ones often languish unseen within the FDA, which regards them as proprietary and therefore confidential. This practice greatly biases the medical literature, medical education, and treatment decisions.
Kirsch and his colleagues used the Freedom of Information Act to obtain FDA reviews of all placebo-controlled clinical trials, whether positive or negative, submitted for the initial approval of the six most widely used antidepressant drugs approved between 1987 and 1999—Prozac, Paxil, Zoloft, Celexa, Serzone, and Effexor. This was a better data set than the one used in his previous study, not only because it included negative studies but because the FDA sets uniform quality standards for the trials it reviews and not all of the published research in Kirsch’s earlier study had been submitted to the FDA as part of a drug approval application.
Altogether, there were forty-two trials of the six drugs. Most of them were negative.
When, for example, an SSRI antidepressant like Celexa increases serotonin levels in synapses, it stimulates compensatory changes through a process called negative feedback. In response to the high levels of serotonin, the neurons that secrete it (presynaptic neurons) release less of it, and the postsynaptic neurons become desensitized to it. In effect, the brain is trying to nullify the drug’s effects. The same is true for drugs that block neurotransmitters, except in reverse ... Getting off the drugs is exceedingly difficult, according to Whitaker, because when they are withdrawn the compensatory mechanisms are left unopposed. When Celexa is withdrawn, serotonin levels fall precipitously because the presynaptic neurons are not releasing normal amounts and the postsynaptic neurons no longer have enough receptors for it. Similarly, when an antipsychotic is withdrawn, dopamine levels may skyrocket. The symptoms produced by withdrawing psychoactive drugs are often confused with relapses of the original disorder, which can lead psychiatrists to resume drug treatment, perhaps at higher doses.Some thoughts:
- I'm not trying to convince anyone to go off antidepressants. "It's complicated." I know a lot of people who take them. I've also seen antidepressant withdrawal firsthand and it isn't pretty.
- A friend of mine who shall remain anonymous recently remarked that among a group of close friends, the ones on antidepressants are all doing well in terms of their careers and general life progress, while the ones who are not are semi-flailing. I wondered at the time if this might be a correlation effect, similar to what's been demonstrated through carefully controlled studies with multivitamins: The act of taking vitamins doesn't seem to actually improve health, but being the type of person who takes vitamins does. I wonder if being the type of person who would seek out therapy/elect to take antidepressants helps alleviate depression (it demonstrates self-awareness and a proactive stance toward your happiness)?
- You've heard me bang my drum about saturated fat and salt intake before (like Stephan Guyenet I think America has been getting nutrition totally wrong for 30-40 years) but there's a bunch of other "common sense" health stuff that we all do blindly even though there's no convincing evidence to support it. Recently I read that it's actually unclear whether we should try to reduce a fever (it's your body trying to kill off an infection). Unless it's high enough to cause brain damage, some people think it's better to let the fever run its course. But there's never been a controlled trial to determine which is better. Some researchers once initiated a trial in which hospital patients with fevers were either treated with fever reducers or allowed to remain febrile. But midway through the trial, some number of the patients who were treated for fevers died. So the researchers panicked and stopped the trial! The upshot of course is that we keep on treating fevers. Now what kind of sense does that make?
- There was an interesting article in a recent issue of Rice Magazine (my alumni magazine!) about the burgeoning field of "health economists," who research why health care costs are skyrocketing in the U.S. without actually improving outcomes. (Sometimes-nutjob Robin Hanson is also interested in this topic.) Key quote: "Costs continue to rise because doctors and hospitals are rewarded for performing more services, not for improving patient health." (You can read the article online here. Click the image and navigate through the magazine; you can click it again to zoom to full screen.) Am I the only one who finds this stuff endlessly fascinating/enraging?