Dr. McGlashan Replies

To the Editor: Dr. Block is correct that our article lacked discussion of the ethics of giving nonpsychotic patients a neuroleptic. This was not for any lack of the importance of the issue but for reasons of space and because considerations of this issue had already been published (1 , 2) .

Dr. Block is incorrect in asserting that the persons in our clinical trial were placed on a neuroleptic “without a clear indication.” These treatment-seeking persons were assessed reliably as being prodromal, i.e., as possessing clinical signs and symptoms indicative of being at substantial risk of becoming psychotic within the ensuing year. While that does not constitute a DSM-IV diagnosis, we do regard it as a clear indication, at least for conducting research to tease forth data concerning the risks and benefits of treatment intervention. We were not treating psychosis, but we had a clear hypothesis that the medication might prevent progression to psychosis. Thus, we were in ethical equipoise with regard to a testable hypothesis. This was recognized by the approving medical ethics boards of the study’s collaborating institutions.

If by “doing no harm” Dr. Block means doing nothing, including doing no research, then we vigorously disagree with his position. Doing nothing certainly protects the false positive prodromal individual from the dangers of side effects, but it does nothing to protect the true positive prodromal individual from the dangers of an unmonitored and untreated first psychosis. In such a situation, the edict of “do no harm” translates quickly into a question of greatest harm: side effects or psychosis. In our view, the fact that we can now reliably identify persons who have a substantial, i.e., nonnegligible, chance of becoming psychotic in the near future has made treatment research with such persons an ethical necessity.

Prevention is a new concept to psychiatry. We are used to functioning as post hoc diagnosticians and interventionists. Prevention interventions are common in other medical specialties and, by definition, they involve prescribing active treatments to a mixture of true positive and false positive persons. The clearest example is cholesterol lowering pharmacotherapy. As prevention, the strategy treats risk (high cholesterol) not disorder (coronary heart disease), and the vast majority of those treated are false positives.

We do agree with Dr. Block’s air of caution insofar as we feel that prevention treatment in schizophrenia, especially pharmacotherapy, belongs in the experimental domain for now. At this stage, our field possesses insufficient data to articulate specific treatment guidelines for those prodromally at risk beyond careful longitudinal monitoring and support (3) . More research is needed to address this novel situation.