Dr. Kopelowicz and Colleagues Reply

To the Editor: We thank Dr. Rifkin for his interest in our article. He correctly notes that the deficit group (those with primary negative symptoms) in our study not only failed to show improvement in negative symptoms but also showed no improvement in positive symptoms. In contrast, the nondeficit group (those with secondary negative symptoms) improved in both positive and negative symptoms. Rather than conclude that olanzapine had a differential effect on primary and secondary negative symptoms, he suggests an alternative explanation—namely, that negative symptoms improve only when positive symptoms improve.

Dr. Rifkin anticipates our first response to his alternative interpretation of our results by noting in his letter that, by definition, primary negative symptoms do not come from positive symptoms. However, he claims that this assertion lacks empirical proof. In fact, this assertion has substantial empirical support from a number of studies conducted over the past 15 years by the University of Maryland group (1–5). Moreover, the results of our own study do not support the conclusion that olanzapine improved negative symptoms only when positive symptoms improved, even in the nondeficit group. In fact, we reported that positive symptom change, by itself, did not predict change in negative symptom score (p. 990). We believe that the most parsimonious explanation for our findings is that 1) olanzapine was effective in treating secondary negative symptoms because of its efficacy for positive symptoms and depressive symptoms, as well as its low propensity to cause extrapyramidal side effects, and 2) primary negative symptoms did not respond to treatment with olanzapine.