Clozapine versus typical neuroleptic medication for schizophrenia

Long-term drug treatment of schizophrenia with conventional antipsychotics has limitations: 25-33% of patients have illnesses that are treatment-resistant. Clozapine is an atypical antipsychotic drug, which is claimed to have superior efficacy and to cause fewer motor adverse effects than typical drugs for people with treatment-resistant illnesses. Clozapine carries a significant risk of serious blood disorders, which necessitates mandatory weekly blood monitoring at least during the first months of treatment.

To evaluate the effects of clozapine for schizophrenia in comparison to typical antipsychotic drugs.

Publications in all languages were searched from the following databases: Biological Abstracts (1982-1999), The Cochrane Library CENTRAL (Issue 2, 1999), Cochrane Schizophrenia Group's Specialised Register (1999), EMbase (1980-1999), ISI Citation Index, LILACS (1982-1999), MEDLINE (1966-1999), and PsycLIT (1974-1999). Reference list screening of included papers was performed. Authors of recent trials and the manufacturer of clozapine contacted.

All randomised controlled trials comparing clozapine with typical antipsychotic drugs were included by independent assessment by at least two reviewers.

Data were extracted independently by at least two reviewers. Authors of trials published since 1980 were contacted for additional and missing data. Odds ratios (OR) and 95% confidence intervals (CI) of homogeneous dichotomous data were calculated with the Peto method. A random effects model was used for heterogeneous dichotomous data. Where possible the numbers needed to treat (NNT) or needed to harm (NNH) were also calculated. Weighted or standardised means were calculated for continuous data.

Currently the review includes 31 studies, 26 of which are less than 13 weeks in duration. These studies include 2589 participants, most of whom were men (74%). The average age was 38 years. There was no difference in the effects of clozapine and typical neuroleptic drugs for broad outcomes such as mortality, ability to work or suitability for discharge at end of the study. Clinical improvement was seen more frequently in those taking clozapine (random effects OR 0.4 CI 0.2-0.6, NNT 6) both in the short and the long term. Also, in the short term, participants on clozapine had fewer relapses than those on typical antipsychotic drugs (OR 0.6 CI 0.4-0.8, NNT 20 CI 17-38), and this may be true for long-term treatment as well. Symptom assessment scales showed a greater reduction of symptoms in clozapine-treated patients. Clozapine treatment was more acceptable than low-potency antipsychotics such as chlorpromazine (OR 0.6 CI 0.4-0.9) but did not differ from acceptability of high-potency neuroleptics such as haloperidol (random effects OR 0.8 CI 0.4-1.5). Clozapine was more acceptable in long-term treatment than conventional antipsychotic drugs (random effects OR 0.4 CI 0.2-0.7, NNT 6 CI 3-111). Patients were more satisfied with clozapine treatment (OR 0.5 CI 0.3-0.8, NNT 12 CI 7-37), but they experienced more hypersalivation, temperature increase, and drowsiness than those given conventional neuroleptics. However, clozapine patients experience fewer motor side effects and less dry mouth. The clinical efficacy of clozapine was more pronounced in participants resistant to typical neuroleptics in terms of clinical improvement (random effects OR 0.2 CI 0.1-0.5, NNT 5 CI 4-7) and symptom reduction. Thirty-two percent of treatment resistant people had a clinical improvement with clozapine treatment.

This systematic review confirms that clozapine is convincingly more effective than typical antipsychotic drugs in reducing symptoms of schizophrenia, producing clinically meaningful improvements and postponing relapse. Patients were more satisfied with clozapine treatment than with typical neuroleptic treatment. (ABSTRACT TRUNCATED