Clozapine shows promise as second-line antipsychotic therapy

In patients with first-episode psychosis who did not respond to initial antipsychotic treatment, the use of clozapine appears to improve clinical outcomes better than olanzapine and amisulpride, according to a study.

The study was conducted in two phases and involved patients aged 16–45 years who had a first-episode psychosis (schizophrenia, schizophreniform disorder, or schizoaffective disorder). In the first phase, the patients were randomly assigned to receive initial treatment with oral olanzapine, risperidone, amisulpride, aripiprazole, or perphenazine for 8 weeks. In phase 2, those who showed no treatment response at week 8 were rerandomized to another 8-week treatment with olanzapine, amisulpride, or clozapine.

The primary outcomes included symptomatic response (ie, ≥40-percent reduction in Positive and Negative Syndrome Scale [PANSS] total score) and time to all-cause discontinuation (ie, discontinuation of antipsychotic drugs for any reason).

A total of 654 patients (mean age 26.9 years, 50.2 percent male) participated in the study, among whom 556 (85.4 percent) completed phase 1 and 359 (55.1 percent) responded to treatment. Response rates were 60.5 percent with olanzapine, 63.4 percent with risperidone, 61.8 percent with amisulpride, 44.3 percent with aripiprazole, and 45.7 percent with perphenazine (p=0.001).

Of the 111 nonresponders, 41 received olanzapine, 38 received amisulpride, and 32 received clozapine in phase 2. Ninety-two of them (82.9 percent) completed 8 weeks of treatment. Response rates were 31.7 percent with olanzapine, 44.7 percent with amisulpride, and 62.5 percent with clozapine (p=0.03).

The present data provide evidence on the efficacy of clozapine as the next sequential treatment after treatment failure with the more traditional antipsychotics.