Augmentation strategies in patients with schizophrenia who show partial response to clozapine treatment: A systematic review

A significant proportion of patients with schizophrenia that receive clozapine remain desensitized with only a partial response. In this group of patients, the outcomes regarding the addition of various psychotropics in combination with 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) are highlighted in this review. The number of controlled studies evaluating augmentation of clozapine in schizophrenia patients is highest for risperidone and lamotrigine add-on treatments. However, the results of recent meta-analyses studies do not support any benefit of either agent combined with clozapine treatment. Some evidence regarding the success of clozapine augmentation with amisulpride, aripiprazole, mirtazapine, omega-3 fatty acids, and ECT have been obtained and ultimately needs further clinical investigation. Current findings from relevant clinical investigations have determined that these studies have limitations consisting of small sample size, variable definitions of clozapine resistance, heterogeneity of outcome measures, and methodological designs. In addition, sufficient evidence does not yet exist regarding the success of various adjunctive treatments for clozapine resistant patients.