Impact of clozapine on negative symptoms and on the deficit syndrome in refractory schizophrenia

Objective: This study compared the effect of clozapine and haloperidol on p ositive and negative symptoms of schizophrenia and in patients with high le vels of negative symptoms or the deficit syndrome. Method: Patients were pa rticipants in a 15-site double-blind, random-assignment Veterans Administra tion trial comparing clozapine (N=205) and haloperidol (N=217) in hospitali zed patients with refractory schizophrenia. Analysis of covariance examinin g change at 6 weeks, 3 months, and 1 year evaluated 1) clozapine's effect o n positive and negative syndromes; 2) clozapine's effect on each syndrome, statistically controlling for the other; and 3) the interaction of clozapin e treatment and the presence or absence of high levels of negative symptoms at baseline and the deficit syndrome. Results: Patients treated with cloza pine showed significantly greater improvement than control subjects on posi tive symptoms at all time points and on negative symptoms at 3 months. Cloz apine had no independent effect on negative symptoms at any time after cont rol for positive symptoms, but its effects on positive symptoms persisted a fter control for negative symptoms at 6 weeks only. There were no significa nt differences in response to clozapine between patients with high and low levels of negative symptoms at baseline or between patients with and withou t the deficit syndrome. Conclusions: The greater effectiveness of clozapine as compared to conventional medications in refractory schizophrenia is not specific to either negative clinical symptoms or clinical subtypes defined by prominent negative symptoms or evidence of the deficit syndrome.