A COMPARISON OF CLOZAPINE AND HALOPERIDOL IN HOSPITALIZED-PATIENTS WITH REFRACTORY SCHIZOPHRENIA

Background Clozapine, a relatively expensive antipsychotic drug, is wi dely used to treat patients with refractory schizophrenia. It has a lo w incidence of extrapyramidal side effects but may cause agranulocytos is. There have been no long-term assessments of its effect on symptoms , social functioning, and the use and cost of health care. Methods We conducted a randomized, one-year, double-blind comparative study of cl ozapine (in 205 patients) and haloperidol (in 218 patients) at 15 Vete rans Affairs medical centers. All participants had refractory schizoph renia and had been hospitalized for the disease for 30 to 364 days in the previous year. All patients received case-management and social-re habilitation services, as clinically indicated. Results In the clozapi ne group, 117 patients (57 percent) continued their assigned treatment for the entire year, as compared with 61 (28 percent) of the patients in the haloperidol group (P < 0.001). As judged according to the Posi tive and Negative Syndrome Scale of Schizophrenia, patients in the clo zapine group had 5.4 percent lower symptom levels than those in the ha loperidol group at all follow-up evaluations (mean score, 79.1 vs. 83. 6; P = 0.02). The differences on a quality-of-life scale were not sign ificant in the intention-to-treat analysis, but they were significant among patients who did not cross over to the other treatment (P = 0.00 3). Over a one-year period, patients assigned to clozapine had fewer m ean days of hospitalization for psychiatric reasons than patients assi gned to haloperidol (143.8 vs. 168.1 days, P = 0.03) and used more out patient services (133.6 vs. 97.9 units of service, P = 0.03). The tota l per capita costs to society were high - $58,151 in the clozapine gro up and $60,885 in the haloperidol group (P = 0.41). The per capita cos ts of antipsychotic drugs were $3,199 in the clozapine group and $367 in the haloperidol group (P < 0.001). Patients assigned to clozapine h ad less tardive dyskinesia and fewer extrapyramidal side effects. Agra nulocytosis developed in three patients in the clozapine group; all re covered fully. Conclusions For patients with refractory schizophrenia and high levels of hospital use, clozapine was somewhat more effective than haloperidol and had fewer side effects and similar overall costs . (C) 1997, Massachusetts Medical Society.