To the Editor: Robert W. Buchanan, M.D., and colleagues (1) conducted an important study on the comparative effect of olanzapine and haloperidol on residual positive and negative symptoms in 63 outpatients with treatment-resistant schizophrenia. They concluded that olanzapine has limited differential benefit for positive and negative symptoms in these patients. However, we think that the correct conclusion must be that olanzapine has no benefit over haloperidol. Namely, the authors could not find superior efficacy for olanzapine for positive and negative symptoms, and the main side effects (extrapyramidal symptoms for haloperidol and weight gain for olanzapine) seem to balance each other out. The authors stated that "the magnitude of weight gain…may potentially offset the more benign extrapyramidal symptom profile of olanzapine" (p. 128). Furthermore, we would like to point out that the mean doses of olanzapine (20.3 mg/day) and haloperidol (18.3 mg/day) resulted in noncomparable dopamine D₂ receptor occupancy. For almost all patients receiving a dose of about 18 mg/day of haloperidol, the balance between efficacy and extrapyramidal side effects is not optimal (2, 3). Haloperidol at lower doses is thought to induce fewer extrapyramidal side effects and fewer neuroleptic-induced negative symptoms and dysphoria (4) without a change in efficacy on positive symptoms (2). Lower haloperidol doses might even further diminish the benefit of olanzapine for extrapyramidal symptoms.

Therefore, the sobering conclusion of this study seems to be that neither olanzapine nor haloperidol shows benefits for outpatients with schizophrenia who met criteria for either residual positive or residual negative symptoms.