Archive 1995–2023

Clozapine is a potent antipsychotic drug recomended for patients with schizophrenia who did not respond to at least two other antipsychotics trials. It has been estimated that 36-67% of patients respond to clozapine however in a substantial proportion the therapeutic effect in not satisfactory. The aim of this paper is to review results of studies regarding the efficacy and safety of clozapine augmentation with other agents. A Medline search identified 8 randomised control trials (RCT) and 18 open studies and case reports on augmentation of clozapine with other antipsychotic or antiepileptic drug. The results of RCT suggest the efficacy of lamotrigine and sulpiride in clozapine- refractory schizophrenia. Only one RCT confirmed the efficacy of clozapine augmentation with risperidone but three other did not support its use. Open studies and case reports suggest that amisulpride, aripiprazole and ziprasidone may also be effective in the menagement of refractory schizophrenia, but results need a confirmation in large RCT. Combination of second generation antipsychotics or antiepileptic drugs and clozapine seem to be well tolerated. The augmentation with risperidone, and lamotrigine did not lead to significant changes of clozapine plasma level. Studies vary in terms of inclusion criteria, duration of previous treatment, dose of clozapine, severity of disease and outcome measures. In most studies conclusions are limited by small sample size.