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Clinical & Research News
Published Online: 21 June 2002

Antipsychotic May Head Off Schizophrenia Development

Thomas McGlashan, M.D., discusses the findings of his team’s groundbreaking work on delaying the onset of schizophrenia. With him is Tandy Miller, Ph.D., who helped develop the interview format and rating scale to identify and measure prodromal symptoms.
Five years ago Thomas McGlashan, M.D., a professor of psychiatry at Yale University, and his colleagues decided to embark on a research project with a different twist by investigating whether giving antipsychotic medication to individuals developing schizophrenia might be able to prevent or delay the onset of the disease (Psychiatric News, March 16, 2001).
McGlashan and his colleagues have now made public the preliminary results from this clinical trial. They reported the results at APA’s 2002 annual meeting in Philadelphia last month. The results are encouraging.
McGlashan and his colleagues first recruited subjects for their trial at four sites—New Haven, Conn.; Chapel Hill, N.C.; Toronto, Ontario, Canada; Calgary, Alberta, Canada—via clinicians, radio ads, and other means. Eventually they identified 60 subjects between 12 and 45 years (the average age was 16 years) who had prodromal symptoms as determined by interviews and rating-scale measures that the Yale team had developed and who did not yet meet DSM-IV criteria for schizophrenia.

Study Background

For instance, most of the subjects had become suspicious of other people. Some three-fourths had become withdrawn socially or participated less in school or sports activities. Some had started hearing imaginary sounds, such as dogs barking, while others had begun to have grandiose ideas, such as believing that if someone touched them, that person would be healed.
The subjects were aware that the phenomena they were experiencing were not normal. What’s more, almost half of the subjects had family members with schizophrenia and were thus concerned about developing the disease themselves. Because of their concerns, they were willing to participate in a trial to see whether antipsychotic medications might be able to prevent it.
The subjects were randomized to receive either an antipsychotic medication (olanzapine) or a placebo for a year. Those getting olanzapine received anywhere from 5 mg to 15 mg daily—on average, 8 mg, which was about half what a typical schizophrenia patient would receive. Neither the subjects nor the investigators knew which subjects were getting olanzapine and which were getting a placebo. The subjects were to be followed up a year after that. The study was also designed so that if any subjects developed frank schizophrenia during its course, they would be removed from the study and given open-label olanzapine (from 5 mg to 20 mg daily).

Results Encouraging

Results from the first eight weeks of the study, with the subjects either taking olanzapine or a placebo, were reported at the APA annual meeting by a member of McGlashan’s team, Scott Woods, M.D., an associate professor of psychiatry at Yale.
The subjects who were taking olanzapine showed a significantly greater reduction in prodromal symptoms from baseline, whereas those on a placebo did not, although these subjects did improve slightly compared with their condition at the start of the study. The subjects on olanzapine, however, had some weight gain.
Whether taking an antipsychotic medication so early in the course of schizophrenia can truly delay the onset of the disease will not become apparent until early fall, when more results are in, Woods told Psychiatric News.
Another psychiatric research group—that of Patrick McGorry, M.D., of the University of Melbourne in Australia—has also been exploring whether giving antipsychotic medication in the prodromal phase can prevent schizophrenia, McGlashan noted. The results of the Australian trial are in press with the Archives of General Psychiatry, he said.
The Yale clinical trial is being funded by a grant from Eli Lilly, the maker of olanzapine. ▪

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Published online: 21 June 2002
Published in print: June 21, 2002

Notes

If persons on the brink of becoming schizophrenic are given antipsychotic medication, might it keep them from actually developing the disease? Preliminary results from a Yale University clinical trial suggest an answer.

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