Friday, July 8, 2011

Do Psychiatric Medications Work?

At the moment the answer is: there is little evidence that they do and some that they cause a great deal of harm. In this essay Marcia Angel reviews three books on psychiatric medications that all argue they are overused and possibly dangerous, and I recommend it to anyone who takes or prescribes them (Part II is here). The basic datum is that despite what we like to think of as "advances in care," the number of people diagnosed with mental illness has risen enormously since World War II, and they stay sick longer. Nobody knows why, although part of the story is certainly better diagnosis and a broader definition of who counts as crazy. Psychiatric drugs may or may not be helping people, but unlike truly effective medications they are not curing anyone.

The first volume is Irving Kirsch's well known book on antidepressants. Kirsch used the Freedom of Information Act to get his hands on all the studies done of the effectiveness of of SSRIs --Prozac, Zoloft, and so on -- not just the ones used to get approval from the FDA. After reviewing them all, he found that the drugs are barely better than placebos at improving the moods of patients. What's more, whatever help they provide seems to be the result of side effects; "active" placebos that cause side effects are just as effective as SSRIs. When I first read this I thought, it can't be true, because I know so many people who have been helped by SSRIs to cope with depression. But there really seems to be no gainsaying Kirsch's science. The brain is a weird thing, and since we really have no idea what causes depression, how can we be sure what helps make it better?

At least Kirsch thinks antidepressants do pretty much nothing; Robert Whitaker thinks they are hurting people. Whitaker thinks that we keep people on psychiatric medications for decades because the drugs are, in effect, addictive. Not only that, but they cause such severe side effects that we have to prescribe other drugs to treat those. The mechanism Whitaker postulates depends on the effects drugs have in the brain. For example, they raise or lower the levels of certain neurotransmitters. The brain responds to this by making more or less of the effected neurotransmitter, leaving the level of chemical in the brain pretty much where it started. Once that new equilibrium is achieved, stopping the drug upsets it, leading in some cases to severe mental problems:
With long-term use of psychoactive drugs, the result is, in the words of Steve Hyman, a former director of the NIMH and until recently provost of Harvard University, “substantial and long-lasting alterations in neural function.” As quoted by Whitaker, the brain, Hyman wrote, begins to function in a manner “qualitatively as well as quantitatively different from the normal state.” After several weeks on psychoactive drugs, the brain’s compensatory efforts begin to fail, and side effects emerge that reflect the mechanism of action of the drugs. For example, the SSRIs may cause episodes of mania, because of the excess of serotonin. Antipsychotics cause side effects that resemble Parkinson’s disease, because of the depletion of dopamine (which is also depleted in Parkinson’s disease). As side effects emerge, they are often treated by other drugs, and many patients end up on a cocktail of psychoactive drugs prescribed for a cocktail of diagnoses. The episodes of mania caused by antidepressants may lead to a new diagnosis of “bipolar disorder” and treatment with a “mood stabilizer,” such as Depokote (an anticonvulsant) plus one of the newer antipsychotic drugs. And so on.
Angel is careful to point out that not all of Whitaker's science is very good, and she has some cogent criticisms. But she seems to agree that there are troubling questions about the harm done by medications whose benefits are hard to pin down.

The third book is by psychiatrist Daniel Carlat, who seems bitterly disillusioned by his profession. He thinks that in an effort to become more like other doctors, and to hold off competition from social workers, psychiatrists embraced drug treatments without much evidence that they work. This left them vulnerable to manipulation by pharmaceutical companies, and the drug companies and the psychiatrists have worked together to keep pumping unproven drugs into vulnerable people:
Why do psychiatrists consistently lead the pack of specialties when it comes to taking money from drug companies? Our diagnoses are subjective and expandable, and we have few rational reasons for choosing one treatment over another.
The picture of psychiatry one gets from these books is not encouraging. The only clear beneficiaries are the pharmaceutical companies, which are making billions. As I said, I know many people who believe they have been helped by psychiatric medications. Some may have been, even if Kirsch is right; if the drugs harm some people, and overall their effect is a wash, they must be helping someone. But overall they seem to do nothing. No other category of psychiatric drugs has been studied as thoroughly as Kirsch studied SSRIs, but the evidence of effectiveness is not very good for any of them. Meanwhile the system trundles on; is it a vast air castle like the humoral medicine of the Renaissance, and are meds our version of bloodletting? Or are we slowly groping our way towards medicine that will really help millions of people lead better lives? Right now, it is hard to say.

'Give me the first thing that comes to hand'; lithograph by Grandville, 1832

5 comments:

Unknown said...

I am left puzzled, because while the thrust of the books seems to be either that SSRIs should be banned or that psychiatry should be abolished, or both, it's quite clear that many people feel they are helped by SSRIs (as you say) and many people feel they have psychiatric difficulties and would like help of the sort a psychiatrist provides. Why then should we take SSRIs or psychiatrists away? I also wonder about the studies that show SSRIs "do nothing." It sounds like these books do muddy the waters, but they are going to have trouble convincing anyone to change things or quit taking their SSRIs, etc., and not just because drug companies et al. have a financial interest in not changing them. Do Kirsh et al. have any persuasive alternative to propose?

In any case, I'm simply befuddled by this idea that a study can "prove" you're not getting a benefit from an SSRI, and this is supposed to motivate a patient who feels they benefit from this type of drug to stop taking it. I strongly suspect one could cite studies that "prove" that caffeine and alcohol have absolutely no effect, that there is no scientific evidence that hamburgers taste good, and that on the whole lobotomy was an extremely helpful treatment.

John said...

Yes, the new version of Seneca's old saw about stupid philosophers is "there is nothing so wrong that some study has not proved it." But Kirsch's review covers a really massive amount of data, and if he found that SSRIs are no better than active placebos, that is hard to refute.

I also wonder what these critics think ought to be done. For one thing, SSRIs may be no better than placebos, but for moderate depression placebos seem to do a lot of good. Widespread belief in the effectiveness of SSRIs, then, may be making a lot of people happier, and Kirsch may therefore be striking a real blow against human welfare.

Maybe what we can hope for realistically is that psychiatrists will react differently to people with severe side effects and ratchet back on medications instead of prescribing more and more.

As an aside, this debate makes me feel differently about the patent medicines of the 18th and 19th centuries. If any psycho-active substance can have a powerful effect on depression, maybe those mild opium concoctions actually did people a lot of good.

Unknown said...

Angel ends her essay by arguing for restraint on the part of psychiatrists, especially in the matters of cocktailing and of diagnosing very young children and then prescribing them powerful medications. That seems sensible, and I certainly wouldn't disagree.

It's the scientific approach that puzzles me. Angel seems to depict the authors as arguing, among other points, that the psychoactives are bad or false because 1) psychiatrists don't know how they work, 2) that they're no better than active placebos, and 3) the goal of psychiatry is to produce "normality."

All of these are flawed in fairly obvious ways. Clearly, not understanding the biochemistry behind an effective treatment is no reason not to use it--did anyone in the 18th century understand "vaccination"? #1 also becomes a problem for #2: does anyone know how placebos work? My understanding is that Kirsch's career-long argument has to do the roles of expectation in determining experience; but does anyone, let alone Kirsch, know how this actually happens?

I'm struck that Angel depicts Kirsch as concluding that, because SSRIs are no better than an active placebo, they therefore produce no benefit. But of course the subjects seem to have reported improved moods. As you suggest, how could that be bad?

I think I'll stop now. My placebo is kicking in, and I feel at peace with all the world.

John said...

You're right, it makes no sense to mix up disputes about the effectiveness of particular drugs with the philosophical question of who is crazy and who needs help. People who go to doctors seeking treatment for depression WANT help, which I think renders arguments about normality pointless.

Anu said...

Please do something to save the people in asylums. Psichiatry should be banned. It is evil and cruel.