Sunday, May 23, 2010

Whitaker's Anatomy of an Epidemic: A Fundamental Challenge to Psychopharmacology

In the course of writing HOOKED and then doing this blog, I thought I was pretty much up on all the misinformation that had been spread about psychiatric drugs. As we've seen in previous posts, we are aware of the lack of evidence to show that mental illnesses result from specific chemical imbalances in the brain, or that psychiatric drugs are targeted to fix those imbalances. We are aware that drugs touted as almost free of serious side effects actually have an array of serious side effects. We have seen that drugs advertised as non-habit-forming in fact pose serious withdrawal risks.

I have just finished reading Robert Whitaker's Anatomy of an Epidemic, and have concluded that we don't yet know the half of it.

Whitaker's message is such a fundamental challenge to today's practice of psychiatry that I went searching on the web for any evidence that he's connected with Scientology or any of its fellow travelers. I found no such evidence (and will mention later how Whitaker's assertions part company with the wacko claims of the anti-psychiatry groups). Whitaker is a journalist and author of a previous book, Mad in America.

I have to explain first Whitaker's assertions about psychotropic drugs, and then his claims about the role of Pharma and psychiatry in misleading us about them.

Whitaker starts off with an epidemiological question. If you go back about 60 years, you discover that relatively few people in the US were diagnosed with mental illness, and that they often recovered and went back to leading normal lives in the vast majority of cases. A tiny percentage made up the chronically mentally ill that were warehoused in state hospitals. Then came the psychopharmacology revolution and the discovery of all the modern classes of psychotropic drugs. We have been told that these drugs revolutionized psychiatry and allowed those "warehoused" people to come out of the hospital and into the community. But when we look at the numbers we see a surprising thing. Not only are many more times the old number of people being diagnosed today with mental illness, but their long term prognosis seems to be abysmal, with a great many ending up on disability. If these new drugs do such a great job, how come we have so many more mentally ill and they do so much worse?

Whitaker then offers an answer, in terms of both basic biological mechanisms and actual patient outcome data. The mechanism answer is a great embarrassment to me personally because I never thought of it, despite having had what I thought was a good biology education in college and even writing papers about systems biology. The standard psychiatric theory, which seems correct, says that the new drugs alter the levels of neurotransmitters in the synapses between brain cells. Anyone with an ounce of knowledge of biology ought then to ask--and what happens next? Just about the fourth or fifth word we learned in biology class is homeostasis. If something comes along from the outside and disrupts any body system, the body almost always has a built-in regulator that seeks to restore the prior state of balance. And indeed, Whitaker tells us, scientists who have gone looking have found the homeostatic responses to these drugs. If the drug results in(say) an increase in dopamine in the synapse, the brain down-regulates its dopamine system, by putting out less dopamine from the first neuron, or by shutting down some of the dopamine receptor sites in the second neuron. In short, the drug, that was supposed to be correcting a disorder (which was actually not the cause of any mental illness anyway according to the best current evidence) has actually now induced a brain disorder.

Homeostasis works for a while, but if you stay on the drug long term, homeostasis eventually poops out. So what happens to people on the drug long-term may look quite different from what happens in the short-term. In any event we have mechanisms that can explain why you actually might induce a brain disorder from using these medications, rather than relieving an existing disorder.

That's at the mechanism level; what about with real people? Whitaker marshals a good deal of evidence from legitimate scientific studies to show that indeed, what the mechanism hints at is what happens. A regular refrain in the book is that there remains about 20% of patients who seem to need the medications and who do much better with them than without them. (That seems clearly to me to show that Whitaker has no truck with the Scientology line.) What about the other 80%? These people may have less symptoms for the first 6-8 weeks or so of treatment, and indeed most controlled trials confirm that advantage. However, after that initial response, the advantage seems to disappear. People treated with medication initially tend to do markedly worse at 1, 2, 5, and 10 years out from initiation of treatment compared to the few patients who somehow escape drug treatment. The standard psychiatric theory is that we see many more people today with bipolar disorder than in the past because when they go into the depression phase of the disorder, psychiatrists treat them with antidepressants, and they then develop symptoms suggestive of mania, meaning that the antidepressants have "unmasked" the true, underlying disease. Whitaker reviews data suggesting that it is much more likely that the antidepressants caused the manic reaction, and that a person who becomes bipolar following medication use cycles more rapidly in and out of mania and depression, and ultimately has a much poorer prognosis, than the classic bipolar patient of days gone by.

How good are the data Whitaker cites? Not knowing the psychiatric literature as a whole, I cannot exclude the possibility that he has carefully cherry-picked a set of studies that happen to confirm his thesis while ignoring a much larger body of studies that disprove it. I tried to get some input from psychiatrist friends but none had as yet read the book. So I remain open to being shown the error of my ways on that point.

Whitaker thus paints a picture by which the standard psychiatric practice has helped a few but has greatly harmed many others. He claims this has happened becaue we as a society have been systematically lied to about the data. The next question is how that set of lies came about.

(A brief detour here to do the "don't try this at home" disclaimer. If you are taking psychotropic drugs and read Whitaker's book, the first thing that crosses your mind is to stop taking the drugs. Do not do that. Quite apart from the fact that you might be among the 20% who do better with the drugs, a quick withdrawal will almost guarantee worsening and a greater dependency on drugs in the future. (Indeed, the standard belief system of psychiatry holds that we know psychiatric drugs do good, precisely because withdrawal worsening is so common.) Only slow, cautious drug withdrawal seems to work for most people.)

In writing HOOKED, I had a standard model of the medicine-Pharma relationship that I thought was based on historical research and fact. I assumed that the heavy financial entanglement between docs and drug companies today was a very slow, almost imperceptible process that occurred throughout the 20th century. The gradual nature of the entanglement explained why docs seemed to have developed no moral compass to guide them when things got seriously out of kilter.

Whitaker paints quite a different picture of the situation with psychiatry. He reminds us first how beleagured the field felt itself to be back in the late 1960s and early 1970s. First, internally, a pitched battle was beign fought among three camps--the newer drug-oriented shrinks; the traditional Freudians who sneered at drugs; and the emerging cadre of social psychiatrists who thought that environmental factors were more important in both causing and treating mental illness. From the outside, psychiatry was threatened with losing all its business as psychologists, psychiatric social workers, and other non-physician counselors set up shop and offered psychotherapy at lower rates. Finally, in academic circles, psychiatry was under attack from the anti-psychiatry movement of folks like Thomas Szasz (The Myth of Mental Illness), R.D. Laing, and, in popular culture, the film One Flew Over the Cuckoo's Nest.

The American Psychiatric Association responded to all this with what looks, for all intents and purposes, like a PR and marketing effort worthy of Toyota's recent efforts to restore America's confidence in its vehicles. Far from any "incremental" change, the dates at which all this happened can be readily determined, says Whitaker. It was in 1974 that the APA formed a task force to explore the possibility that the field could benefit from a large influx of Pharma dollars; and it was in 1980 that the APA adopted a new policy of encouraging drug companies to sponsor "scientific" talks at APA conventions.

Thus, says Whitaker, was formed an alliance unified to get the message out about the goodness of psychotropic drugs and the "chemical imbalance" view of mental illness. The APA and the drug companies both did their part in PR and public "education," and in suppressing as much as possible the dissemination of research results that did not hew to the party line. The NIMH joined forces by deciding that it should be a cheerleader for psychiatry; NIMH officials who harbored doubts about long term efficacy of drugs were forced out and few studies looking at dangers of drugs long-term, or nondrug treatment alternatives, could get funding. Finally, NAMI (National Alliance on Mental Illness), the grass-roots organization of patients and relatives, bought the claim that anyone who doubted the chemical-imbalance theory was denying that mental illness existed and telling NAMI members that your kid did not have a real mental illness, so it must be instead that you're just a bad parent. And of course the drug companies made sure generously to fund NAMI. (In light of this history the recent moves of the APA to distance itself from Pharma funding are even more noteworthy.)

Whitaker notes that the conventional party line has been so successful that he has had a great deal of trouble finding working examples of how mental illness, in his view, actually ought to be treated. He cites a handful of programs in Finland and the U.S. that do it the right way, starting off with nondrug approaches that stress human engagement with and human regard for the patient, and that resort of drugs only in the minority of cases that do not respond to repeated nondrug efforts. (The programs then try hard to get the patients off drugs after the initial symptoms resolve.) Again, to me, the recommendations he offers for solutions clearly put distance between him and disreputable sources such as Scientology.

Botton line-- this book poses serious challenges to many of our presuppositions. I await more insights from others as to its reliability.

Whitaker R. Anatomy of an Epidemic: Magic Bullets, Psychiatric Drugs, and the Astonishing Rise of Mental Illness in America. New York: Crown, 2010.


Joseph P. Arpaia, MD said...

Thanks for your thorough review of Whitaker's book. What you describe makes a lot of sense. I'll have to get the book.

It should be obvious that we don't have the answers in psychiatry. After all, when antibiotics were discovered the mortality and morbidity of bacterial infections plummeted. The claim that we are seeing more mental illness because we are screening more effectively is pure BS. If we had effective treatments, then the prevalence would plummet.

It was pretty obvious to me in residency that the mono-amine theory had about the same scientific legitimacy as the humoral theory of disease in the Middle Ages. Actually they were one up on the shrinks because they had four humors (blood, black bile, yellow bile, and phlegm) and we had only three (serotonin, dopamine, and norepinephrine).

I was fortunate to be doing research in a lab which studied neuropeptides and with over 50 known neuropeptides it was obvious that we knew next to nothing about how the brain really worked.

When we look at the neuroendocrine system as a set of processes which enables the person to respond effectively to their environment, and realize that these processes are constantly adapting and learning, then its pretty straightforward to develop non-pharmacologic techniques that work, and augment those with medications when necessary.

I think an alternative to the "medical" model is to use "learning" model in psychiatry, which I call "behavioral medicine" for lack of a better word. Perhaps "applied psychoneuroendocrinology" might be more accurate.

In this both classical and operant conditioning are used to evoke sustained changes in the neuroendocrine responses. Since these can be measured in real-time using pretty simple equipment, heart-rate monitor, heart-rate variability, skin conductance, muscle tension, etc. we can make sure that the techniques are working.

With this approach even when patient need medications they use lower doses, fewer meds, or (if already on them) decrease or come off altogether without relapsing once they have learned the requisite skills.

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altostrata said...

What a relief to see the truth finally coming out about psychiatry, with a steady stream of well-researched books.

As far as withdrawal is concerned, I urge everyone to visit, a non-commercial patient support site for gradual withdrawal from all types of psych drugs, not just Paxil.

There are thousands of case reports of withdrawal syndrome misdiagnosed as "relapse" or "unmasking" of prior severe mental illness -- actually iatrogenic damage to the autonomic nervous system caused by psych drugs.

Although psychiatry traffics almost exclusively in drugs that are truly addictive or cause physical dependency, it takes no responsibility whatsoever for safe withdrawal from the medications. It's as though doctors expect patients to be medicated forever.

It's been left up to patients to support and educate each other in safely tapering, which can last months or even years.

As a result of inadequate tapering in withdrawal -- and this is a connection yet to be drawn -- much of the "relapse" in mental disorders is iatrogenic.

See the recent paper Am J Psychiatry, May 17, 2010 Illness Risk Following Rapid Versus Gradual Discontinuation of Antidepressants, Baldessarini, et al., which only scratches the surface of the problem.

Personally, I have been suffering from Paxil withdrawal syndrome for 5.5 years and been disabled by it for most of the last 3 years. My inadequate taper was "supervised" by UCSF Psychiatry staff.

The damage, as in most cases of withdrawal syndrome, is glutamatergic disinhibition leading to various autonomic dysfunctions. Common attendant symptoms of anxiety, insomnia, tachycardia, etc. are often misdiagnosed as "unmasking" of bipolar disorder or even psychosis and medicated unmercifully, further damaging the nervous system and sending the patient on a merry-go-round of psychiatric drugs, incompetent medical care, and chronic illness.

Mark McConnell said...

Howard, thank you for this review. It reminded me that I've wondered if anyone (perhaps you?) have graphed:

X axis: time...1900-Current
Y axis: % of drugs that can be considered "breakthroughs" or "significant advances"

Defining "breathroughs" would certainly be somewhat arbitrary but the point I'd like to explore is whether we, as prescribers and society, look at new drugs (which are often not breakthroughs) through the lenses of a perspective influenced by the dramatic impact of penicillin, INH, etc.

Howard Brody said...

Mark-- you ask a great question and I have never seen this exercise carried out from 1900-2010. I know it has been done roughly between 1980 and 2010 and has revealed a steady drop off in percent of new drugs that reprsent real therapeutic advances. My qualitative sense is that this follows a boom period of 1945-1980 during which a great many real advances appeared. It would seem logical to me that pharmaceutical science would NOT advance steadily but would wax and wane depending on both luck and the underlying science. When some real breakthroughs in our basic understanding of disease mechanisms occur (as presumably happened between the 1920s and 1960s), after a suitable lag period, one would then expect a raft of new, useful drugs to appear. Once we have picked the low hanging fruit from that phase of scientific advance, it would seem reasonable to expect that breakthrough drugs would get harder and harder to find, until the next wave of basic advance in understanding of mechanisms. Whitaker's book contributes to this discussion the claim that psychiatric drugs between 1950 and 2010 did not really form a part of this pattern due to the fact that we have never yet been able to pinpoint a chemical reaction in the brain that causes any mental illness, and then design a magic-bullet drug to reverse that chemical reaction. In each case, drugs that turned out presumably to be useful for psychiatric conditions were drugs initially developed for other purposes, that were then discovered mostly by chance to alter mental states.

Tyson said...

Thank you for your article. Very informative.

Franco said...

Stimulants are a large factor in my community