To the Editor: The use of placebo in clinical trials of new medications has long been considered a crucial part of research methodology. However, the need to safeguard the rights of research subjects and to obtain their informed consent raises several ethical concerns about the appropriateness of double-blind placebo studies of the treatment of schizophrenia. These concerns relate primarily to the ethical principles of beneficence and respect for patient autonomy.
The report of the North American double-blind olanzapine studies by Dellva and associates (1) in the December 1997 issue exemplifies current psychopharmacological research involving the use of placebo in the treatment of adult patients with schizophrenia. This two-part multicenter study offers conclusive findings about the long-term efficacy of standard-dose olanzapine maintenance therapy compared with very-low-dose olanzapine, haloperidol, or placebo.
In the first part, or acute phase, of the study, a one-year relapse risk of 28.6 percent was found for patients treated with standard-dose olanzapine, while a relapse risk of 69.9 percent was found for patients treated with placebo (2).
According to the ethical principle of beneficence, potential benefits must be derived from research, while the principle of autonomy requires real concern for subjects' self-determination (3). In light of these principles, are subjects with schizophrenia adequately informed that those receiving placebo might derive little or no benefit from participation in a study?
Seven specific ethical questions can be raised about double-blind studies in which patients with schizophrenia receive placebo rather than a standard antipsychotic medication. They are as follows:
• Do study participants fully understand the need for continued antipsychotic medication in order to prevent relapse and rehospitalization?
• Do subjects realize that decrements in functioning may accompany continued acute psychotic episodes?
• Due to the prevalence of thought disorder and other symptomatic features, is subjects' competency to give informed consent assessed by neutral examiners?
• Given the prevalence of cognitive deficits in schizophrenia, are subjects evaluated for the presence of cognitive deficits as impediments to understanding informed consent?
• Are subjects who show marked cognitive deficits, for example, in attention and memory, treated differently than other subjects or given remedial training that might facilitate their better understanding of the informed consent process?
• Are subjects with schizophrenia who receive placebo and suffer relapse ever informed that being treated with placebo had questionable efficacy?
• Finally, who is ethically and financially responsible for rehospitalizations that might not have been necessary if standard antipsychotic medications had been used?
Recast from the perspective of the subjective experience of consumers, these ethical questions can be restated in simple terms: how would investigators feel about a family member with schizophrenia being treated with placebo if he or she might respond favorably to standard antipsychotic medication?
Elucidation of the roles of new antipsychotic medications and the factors that contribute to treatment failures must be balanced against any potential threats to autonomy and ill effects from the use of placebo in patients with schizophrenia.
Dr. McCarthy is chief of psychology at Queens Children's Psychiatric Center in Bellerose, New York.