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MindView Director's Letter
Progress with Antipsychotic Medication
Spring 2007
Archived Letters
Recent large clinical trials from the United States and the United Kingdom have provided valuable
information for clinicians, patients, and family members. The largest, called CATIE (Comparative
Antipsychotic Trials of Intervention Effectiveness) was an NIMH study that compared the effectiveness
and side effect profile of one older and several newer antipsychotic medications on more
than 1400 individuals with schizophrenia. The first results were published over a year ago and are
somewhat surprising. The surprising part is that perphenazine did as well as most of the other medications
in both effectiveness and side effects. Other findings suggested that there was widespread
dissatisfaction with antipsychotics since most of the patients switched to another medication within
the first few months. In addition, the medication which came out the best with regard to effectiveness,
olanzapine, also had serious side effects. Olanzapine-treated patients gained an average of two pounds per month and had elevations in lipids and triglycerides. The study results were widely publicized as indicating that the drug companies had grossly distorted the evidence in order to promote the more expensive newer drugs.
The results of the trial emphasize why the drug treatment of schizophrenia and other psychotic illnesses can be so difficult. Antipsychotic treatment would be relatively easy if the most effective antipsychotic also had the mildest side effects. Phase 1 of CATIE shows that it is just the opposite. This unfortunate trend is also apparent in a Phase 2 study that included patients who discontinued their medications in Phase 1 because of lack of effectivess. In this study, clozapine was clearly the most effective for
this population of patients who were not adequately treated during the first phase. Clozapine was also associated with substantial weight gain and other side effects. A study from the United Kingdom also found that the effectiveness of newer and older antipsychotics was similar and that clozapine was superior in effectiveness.
The study provides valuable information, but can be misinterpreted. First, the patients who were in the study may not be typical of patients who are treated in many settings. These were individuals who had been ill for an average of more than 15 years and had still not found a drug they with which they were pleased. These were patients with illnesses that were only partially responsive to their medications or patients who were sensitive to side effects. If they were doing well, they would not have entered the trial. In addition, they study was too brief to measure whether there were difference in the risk for tardive dyskinesia, a serious side effect that occurs less often on newer drugs.
These studies should not be used as evidence that patients should have fewer antipsychotic choices. The available antipsychotics are not interchangeable since they have different side effect profiles. Although some patients may do well on the older drugs, others will be tormented by discomforting side effects and some may be more likely to develop tardive dyskinesia. The decision which drug to take should probably occur in an environment that permits open discussions about how the patients feels on medication.
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Archived Letters
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