Ethical Concerns Regarding Olanzapine Versus Placebo in Patients Prodromally Symptomatic for Psychosis

To the Editor: I am concerned that the article entitled “Randomized, Double-Blind Trial of Olanzapine Versus Placebo in Patients Prodromally Symptomatic for Psychosis” (1) lacked discussion regarding the ethics of treating young (average age=18.2 years) and nonpsychotic patients with the neuroleptic olanzapine for 1 year.

The authors anticipated this problem, and, as they point out, in prior studies 46%–80% of those labeled “prodromal” never develop schizophrenia after up to 2 years of observation and were probably false positives (p. 797). In their study, 16 of 29 participants (55%) in the placebo group never became psychotic after 2 years. We should, therefore, expect that approximately 17 of the 31 (55%) subjects who were given olanzapine were also false positives. More than one-half of the patients who were prescribed olanzapine were exposed to it unnecessarily—at doses ranging from 5 to 15 mg/day.

In addition to the patients’ average weight gain of 19 lbs, I am concerned with what other biopsychosocial repercussions there were for these young men and women after they were placed on the neuroleptic, without a clear indication, for a year. Isn’t our first and foremost obligation to “do no harm”?