Clozapine and haloperidol in moderately refractory schizophrenia - A 6-month randomized and double-blind comparison

Background: Despite the demonstrated efficacy of clozapine in severely refr actory schizophrenia, questions remain regarding its efficacy for primary n egative symptoms, comparison With a moderate dose of a first-generation ant ipsychotic, and adverse effects during a longer-term trial. This study exam ined its efficacy in partially responsive, community-based patients, compar ed clozapine with moderate-dose haloperidol, and extended treatment to 6 mo nths. Methods: Randomized, double-blind, 29-week trial comparing clozapine (n = 3 7) with haloperidol (n = 34). Subjects with schizophrenia who were being tr eated in community settings at 3 collaborating clinical facilities were enr olled. Results: Subjects treated with haloperidol were significantly more likely t o discontinue treatment for lack of efficacy (51%) than were those treated with clozapine (12%). A higher proportion of clozapine- treated subjects me t an a priori criterion of improvement (57%) compared with haloperidol-trea ted subjects (25%). Significantly greater improvement was seen in symptoms of psychosis, hostile-suspiciousness, anxiety-depression, thought disturban ce, and total score measured on the Brief Psychiatric Rating Scale. No diff erences were detected in negative symptoms using the Brief Psychiatric Rati ng Scale or the Schedule for Assessment of Negative Symptoms. Subjects trea ted with clozapine experienced more excess salivation, dizziness, and sweat ing and less dry mouth and decreased appetite than those treated with halop eridol. Conclusions: Compared with a first-generation antipsychotic given in a mode rate dose, clozapine offers substantial clinical benefits to treatment-refr actory subjects who can be treated in the community. Advantages are seen in a broad range of symptoms but do not extend to negative symptoms.