How long to wait for a response to clozapine: a comparison of time course of response to clozapine and conventional antipsychotic medication in refractory schizophrenia

This study compared the time course to clinical improvement with clozapine and with conventional antipsychotic medications. A double-blind trial compared clozapine and haloperidol in patients with schizophrenia who were refractory to conventional antipsychotic medication and were hospitalized for 30 to 364 days at 15 Veteran Affairs medical centers during the year before study entry. Patients in the original study were randomly assigned to haloperidol or clozapine and followed for 12 months, at maximum tolerable doses. Patients who completed a full year of treatment with clozapine (n = 122), or with either haloperidol or another conventional antipsychotic medication (n = 123) and who also completed the 9- or 12-month assessment were included. Response to treatment was defined as 20 percent improvement on standard scales of symptoms and quality of life at the latter of the 9- or 12-month interviews. More patients assigned to clozapine achieved 20 percent improvement in symptoms at each followup. Among patients who did not improve at 6 weeks, 3 months, or 6 months, there were no significant differences between clozapine and comparison patients in outcomes at 1 year. Among patients who did improve, maintenance of that improvement also did not differ between the groups at 1 year on symptom measures. Maintenance of improvement in quality of life at 1 year was significantly greater for clozapine patients who had improved at 6 months (p < 0.04). Significant differential symptom response to clozapine occurred exclusively during the first 6 weeks of treatment.