A significant proportion of patients with schizophrenia receiving clozapine remain with partial response. In this group of patients findings regarding addition of various psychotropics to ongoing clozapine treatment for augmentation are controversial. In this review, literature regarding the efficacy and safety of adjunctive agents in clozapine resistant schizophrenic patients is examined. Augmentation agents added to clozapine in treatment resistant schizophrenic patients consist of antipsychotics, antidepressants, mood stabilizers, other agents (eg. omega 3 fatty acids and glutamatergic agents) and electroconvulsive therapy (ECT) in this review. The number of controlled studies evaluating augmentation of clozapine in schizophrenia patients are highest for risperidone and lamotrigine add on treatments. However, the results of recent meta-analyses studies do not support any benefit of either agent as adjunct to clozapine treatment. Some evidence regarding the success of clozapine augmentation with amisulpride, aripiprazole, mirtazapine, omega 3 fatty acids and ECT have been obtained which needs further clinical investigation. Current findings from relevant clinical studies point that theses studies have limitations of small sample size, variable definitions of clozapine resistance, heterogenity of outcome measures and methodological designs and that sufficient evidence does not yet exist regarding the success of various adjunctive treatments for clozapine resistant patients.
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