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Why is the success rate that people recover from schizophrenia higher in cultures that don't use psychotropic medications to treat it?

Crossville, Tennessee

Answered by Robert Whitaker:
This is the question that got me interested in this subject nearly four years ago.

In the 1970s, the World Health Organization conducted its first study comparing outcomes for schizophrenia patients in "developing" countries with those in the U.S. and other "developed" countries. The study followed patients for five years, and it found that 64% of the patients in the poor countries had outcomes that could be categorized as good at the end of this period, versus 18% in the rich countries. The difference in outcomes was so dramatic that the WHO concluded that living in a developed nation was a "strong predictor" that a schizophrenic patient would never fully recover.

In response to these poor results, some Western psychiatrists argued that the difference wasn't real, and that many people in the poor countries must have been suffering from milder forms of psychotic disorders. So in the 1980s the WHO conducted a second comparative study, paying close attention to this diagnostic question, and came back with the same answer. In this 2-year study, 63% of patients in the poor countries were in the good-outcomes category, versus 37% in the developed countries. Now the WHO didn't come up with a reason for this difference. However, in the second study, it did note that there was a noticeable difference in medication use. In the developing countries, only 16% of patients were routinely kept on antipsychotic mediations, versus 61% of patients in the developing countries.

This raises an obvious question: Was the variation in drug use the reason for the difference in outcomes? I know that it seems like medical heresy, and against all accepted wisdom, to even think that this might be so, but I thought that at least I could look at what our own research showed regarding the use of neuroleptics and long-term outcomes.

Here are some of the main findings in our own research literature that provide, I believe, rather compelling evidence for why poor outcomes would be associated with constant use of neuroleptics. (I should note here that the research below is related to standard neuroleptics --Thorazine, Haldol -- and not to the newer atypicals like risperidone and olanzapine.)

  • Standard neuroleptics work by profoundly blocking dopamine activity in the brain. At a therapeutic dose, they block 70% to 90% of all D2 receptors (this is a particular type of receptor for dopamine). So rather than balance dopamine activity in the brain, standard neuroleptics actually produce a notable deficiency in dopamine transmission. Indeed, it is a deficiency somewhat similar in kind to what occurs in Parkinson's patients, which is why standard neuroleptics so often cause Parkinsonian symptoms. This blockage of dopamine activity is also why many patients on standard neuroleptics complain of feeling empty inside -- dopamine is involved in mounting emotional responses to the world.

  • In 1959, researchers reported that the drugs could cause tardive dyskinesia (TD), a form of often irreversible motor dysfunction. Later, researchers determined that this affected 5% of patients per year, and that the effect was cumulative (10% of patients kept on drugs two years, 15% at end of three years, and so forth.). More than 20 studies have also now found that tardive dyskinesia doesn't simply impair motor movement, but that TD patients are also cognitively impaired on a variety of measures, which include memory, intellectual functions, etc. Some researchers have compared TD to Huntington's disease, or "postencephalitic brain damage."

  • In 1963, the NIMH reported that neuroleptics were better than placebo over a six-week period in reducing psychosis, a study that is still cited today as showing the drugs' efficacy. However, the NIMH then did a one-year followup study of the patients in that first 6-week trial, and they found, much to their surprise, that the drug-treated patients were more likely to have been rehospitalized than those treated with placebo. This suggested that while the drugs produced a short term benefit, over the long-term they actually made people more biologically vulnerable to psychosis. (This long-term study is almost never cited, and was quickly forgotten.)

  • In 1971, the NIMH reported that in a drug-withdrawal study, relapse rates rose in direct correlation to drug dosage, such that the higher the dosage before withdrawal, the greater the relapse rate. This furthered the sense that the drugs were causing some sort of biological change that made people more biologically prone to psychosis. Around this time researchers also reported that it appeared that relapse in drug-treated patients was more severe than relapse in placebo-treated patients.

  • These disturbing results led the NIMH to fund at least three studies in the 1970s that compared treatment with psychosocial care and minimal or no use of neuroleptics with conventional care. Each time relapse rates were lower for the experimental group over follow-up periods ranging from one to three years. The favorable outcomes in these studies led some researchers to conclude that there was, at the very least, a subgroup of schizophrenia patients -- 40% or more of all people so diagnosed -- who could do well without the drugs.

  • In 1979, Canadian investigators put forth an explanation of why the drugs could make people more biologically vulnerable to psychosis. In response to the blocking of dopamine activity, the brain tries to compensate by increasing the number of its dopamine receptors, thus becoming "supersensitive" to this neurotransmitter. Once a person's brain undergoes this change, then he or she is at very high risk of relapse should the drug be abruptly withdrawn. As the Canadian investigators concluded: "Some patients who seem to require lifelong neuroleptics may actually do so because of this therapy." This finding has particular relevance for the sub-group of patients, 40% or more, who had done well in the trials in which they were treated with psychosocial care. They may not have naturally needed neuroleptics, but once they were exposed to the drugs, they would likely find it difficult to get off them, and thus would be pushed along a path that involved lifelong medication, with all its associated problems.

  • In the past decade, there have been several MRI studies that have documented structural changes in the brain associated with neuroleptic use. These drug-induced changes include atrophy (or shrinkage) of the cerebral lobes, and an abnormal enlargement of the basal ganglia area of the brain.

That is the bare outline of the research record involving standard neuroleptics, and it is, I believe, a research record that provides rather convincing evidence of why our Western paradigm of care -- that patients diagnosed with schizophrenia as a matter of course need to take antipsychotic medications indefinitely -- produced the poor outcomes found by the WHO. It's important to reiterate, however, that this is a research record related to standard neuroleptics. One hopes, of course, that long-term outcomes with the newer atypicals will prove much superior, but that research record is still in its early stage.

[Read Dr. John Hsiao's response to a similar question.]

Robert Whitaker

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