Study designs of evaluations included in the review
Case series and case reports were eligible for inclusion in the review.
Specific interventions included in the review
Studies assessing clozapine adjunctive agents were eligible for inclusion. Studies examining electroconvulsive therapy as a clozapine augmentation strategy were not included in the review. The included studies examined the efficacy of sulpride, risperidone, olanzapine, lithium, lamotrigine, fluvoxamine and bromocriptine as adjuncts to clozapine. The dose of clozapine during combined treatment varied from 50 to 900 mg/day and the duration of the combined treatment ranged from 1 week to 15.3 years. Some patients received concomitant medications as well as the study drug of interest. Only 48.5% of patients were reported to have received an adequate duration and dosage of clozapine monotherapy (at least 12 weeks and 300 mg/day).
Participants included in the review
Studies of clozapine-resistant schizophrenic or schizoaffective patients were eligible for inclusion. Twenty-five schizophrenic participants and 8 schizoaffective patients were included in the review. The age of the patients varied from 18 to 60 years across studies. The duration of illness varied from 2.5 to 34 years.
Outcomes assessed in the review
Studies with no efficacy reports were excluded from the review. The outcomes included in the review were clinical outcome, plasma clozapine levels and side-effects. Clinical outcomes was assessed using either the Brief Psychiatric Rating Scale or the Positive and Negative Syndrome Scale, or was judged by subjective clinical impression.
How were decisions on the relevance of primary studies made?
At least three independent reviewers inspected the individual patient data reported in each of the studies before inclusion.