Editor's note: In the October issue, Dr. Glazer offered the first part of his rebuttal to the Ashcraft-Anthony “Tools for Transformation interviews with Robert Whitaker, which appeared in two parts in the July/August and September issues. He focused on three arguments that emerged from these articles:
- That psychiatric medications have increased disability over the last 20 years;
- That there is a pharmacological basis to explain this increased morbidity; and
- That psychiatry conspired with the pharmaceutical companies to keep these “facts” from prescribers and the public.
Dr. Glazer used epidemiologic principles to argue that there are many plausible explanations for the observed rise in psychiatric disability in the past 20 years and that Whitaker's argument that psychiatric medications caused this trend is “speculative.” In this article, he addresses the second and third arguments noted above.
Argument #2: There is a pharmacological basis to explain how psychiatric medications have led to increased disability
To make this allegation, Whitaker tapped into the work of a small coterie of legitimate investigators who have suggested that long-term use of antipsychotic and antidepressant medications may contribute to more psychosis or depression.
Chouinard and colleagues from McGill University in Montreal first suggested that chronic antipsychotic treatment induces relapse in some schizophrenic patients.1 The mechanism of action to explain this phenomenon involved the dopamine receptors of the brain. The idea was that antipsychotic medications blocked dopamine receptors and, in response to that blockade, the neurons developed more receptors, resulting in more psychotic symptoms.
While appealing at first, this idea did not bear out, despite considerable analysis, for several reasons:
So, while this idea received considerable attention in peer-reviewed journals during the 1980s, an authoritative review of the literature concluded in the early 1990s that “research has not established that neuroleptics cause the proposed effect, and considerations of mechanism have not been separated from those of causation.”2
In Part II of the Ashcraft and Anthony articles, Whitaker refers to the work of Martin Harrow and Nancy Andreasen in an attempt to argue that long-term treatment with antipsychotic medications causes increased pathology. The Harrow study, involving a 15-year follow-up of 64 schizophrenic patients, was not an easy study to perform. Twenty of these patients did not receive antipsychotic medications, and the investigators noted that their outcomes were more likely to be better than what was seen in the 44 patients who received antipsychotics. Whitaker argues that this study means that long-term antipsychotics are not necessary, or may be harmful.
In January, Dr. Andrew Nierenberg, Professor of Psychiatry at Harvard Medical School and Massachusetts General Hospital, debated Mr. Whitaker in a grand rounds format sponsored by the Massachusetts General Hospital Department of Psychiatry. In a subsequent interview, Dr. Nierenberg stated, “Mr. Whitaker needs a basic course on principles of epidemiologic research, specifically on the concept of ‘susceptibility bias.’”
Even a casual look at the Harrow study reveals that the patients who were not taking psychiatric medications at 15 years were self-selected; they had exhibited better and earlier prognostic features from the beginning. Yet, Whitaker reverses cause and effect in his argument. Patients who stopped antipsychotic medications did so because they were doing well. Standard clinical logic would conclude that the poor outcomes in the antipsychotic treated patients were a function of their illness, not of their treatment. Would anyone conclude that long-term insulin treatment causes nerve and blood vessel damage in diabetic patients? Or, that chronic use of digitalis causes heart attacks?
Andreasen's studies of brain anatomy have found that the brains of people with schizophrenia who take antipsychotic medications are diminished in size. While this of course is concerning, it must be noted that these brains were compared to those of normal control subjects, not to those of untreated schizophrenia patients. Thus, it is impossible to examine whether it is the medications or the illness that lead to the smaller brain size.
It is worth noting that it would be impossible to get approval from a human investigation committee to follow untreated schizophrenic patients, because withholding such treatment over a long term would be considered unethical. Additionally, brain imaging studies such as the recent one by Malla et al, are adding support to the idea that it is schizophrenic illness, not antipsychotic medications, that causes the observed loss of brain tissue over time.4
One of the best demonstrations of the beneficial impact of long-term antipsychotic therapy can be seen in a study of relapses among 104 newly diagnosed schizophrenic patients who had responded to antipsychotic therapy.5 Over a five-year period, patients treated with antipsychotics were five times less likely to relapse than were patients who stopped such medication. In other words, the risk of schizophrenic relapse was reduced by the use of antipsychotic medications, not increased.