Dr. Buchanan and Colleagues Reply

To the Editor: Drs. de Haan and van Beveren raise two points concerning our recent article on the comparative efficacy of olanzapine and haloperidol for residual positive or negative symptoms. First, they note that in the abstract of our article we stated that “Olanzapine has limited differential benefit for either positive or negative symptoms in patients with treatment-resistant schizophrenia” (p. 124). They suggest that the proper conclusion should be that “olanzapine has no benefit over haloperidol.” The qualification in our statement reflects the fact that our study is not the only one to have addressed this issue. In our Discussion section, we reviewed two studies that asserted a benefit for olanzapine in this population (1, 2). Although we believe that these studies have serious methodological flaws, they remain in contradistinction to our results. Second, Drs. de Haan and van Beveren suggest that the mean doses of haloperidol and olanzapine achieved in our study result in noncomparable D₂ receptor occupancy, with the haloperidol dose associated with increased D₂ receptor occupancy, which could potentially lead to increased extrapyramidal symptoms, dysphoria, and secondary negative symptoms. Although we agree with the theoretical concern, we note that the haloperidol-treated patients did not exhibit a mean worsening of either extrapyramidal symptoms or depressive symptoms (as measured by the Hamilton Depression Scale) nor a worsening of negative symptoms (Tables 2 and 3). The alternative concern, which we raised in our Discussion section, is that the olanzapine dose was relatively low for this population. A higher olanzapine dose may have led to increased symptomatic improvement.