A prospective study of clozapine in treatment-resistant schizophrenic patients

Abstract

Preliminary results of a non-blinded prospective study of the effect of clozapine on symptomatology and social function in 51 treatment-resistant schizophrenic patients are reported. The mean duration of treatment at the time of this report was 10.3 +/- 8.1 months, median 7.6 months. Overall, 3/51 patients (60.8%) showed at least a 20% decrease in total BPRS, a criterion of improvement in the study of Kane et al. (1988). Four of 51 (7.8%) had at least a 50% decrease in total BPRS. Improvements in both positive and negative symptoms were noted. Marked improvements in social function were noted within the first 6 months of treatment. Improvement was first noted at all time points, with only 45.2% of improvers being identified after 6 weeks of treatment. These results suggest a 6-12-month trial may be desirable before deciding to discontinue clozapine because of insufficient response. Higher total Brief Psychiatric Rating Scale (BPRS) score and higher ratings on the Paranoid Disturbance subscales of the BPRS were factors which discriminated clozapine responders from non-responders.

Time to clozapine response in a standardized trial

“…The proportion of subjects who improved in this study (68%, N=34 of 50) is high but still consistent with data reported in other follow-up studies (9,14). The present data were collected with the clinical and research (rating) staff aware that clozapine was the treatment drug, which creates a possible expectancy bias toward response.…”

“…In the U.S. multicenter clozapine study (8), improvement continued to increase steadily in the clozapine-treated patient group for the entire 6-week period, with no plateau in response measures. This has led to a concern that late response might be a characteristic of clozapine treatment (9).…”

“…Meltzer et al (9) described treatment-resistant schizophrenic patients who took as long as from 6 to 12 months to initially respond to clozapine treatment. Mattes (10) stated that continued improvement in patients who respond to clozapine may account for continuing group improvement over time.…”

“…Thus, the duration of a clinically adequate trial of clozapine remains controversial (3), with recommendations that range from several months (5, 15) to 1 year (9). The data reported here are intended to help resolve the issue of the effects of dose and time on clozapine response.…”

Negative symptoms: a path analytic approach to a double-blind, placebo- and haloperidol-controlled clinical trial with olanzapine

“…Unfortunately, the published literature addressing these two differing perspectives has been limited principally to open-label studies (33,34). The present investigation contained several important methodologic improvements: 1) the trial was blind, 2) it contained both an active-drug and a placebo comparison group, 3) the dosing permitted flexibility within a range in order to optimize each individual's dose, 4) the protocol excluded or controlled for other concomitant drug use, 5) it did not permit concurrent nonpharmacologic treatments, and 6) the data analysis strategy included a novel statistical method to differentiate direct versus indirect (or secondary) change in negative symptoms across the randomly assigned treatment groups.…”