Background: Clozapine has been used in treatment-resistant patients with schizophrenia. However, only 40% of patients with treatment-resistant schizophrenia have response to clozapine. Many augmentation strategies have been proposed to treat those clozapine-resistant patients, but the results are inconclusive. In this review, we intended to review papers dealing with the augmentation strategies in the treatment of clozapineresistant patients with schizophrenia. Method: We reviewed randomized, double-blind, placebo-or sham-controlled trials (RCT) for clozapine-resistant patients with schizophrenia in Embase, PsycINFO, Cochrane, and PubMed database from January 1990 to June 2019. Results: Antipsychotics, antidepressants, mood stabilizers, brain stimulation, such as electroconvulsive therapy (ECT) and repetitive transcranial magnetic stimulation, and other strategies, were used as an augmentation in clozapine-resistant patients with schizophrenia. Except for better evidence in memantine with 2 RCTs and cognitive behavior therapy in 2 studies to support its effectiveness, we found that all the other effective augmentations, including sulpiride, ziprasidone, duloxetine, mirtazapine, ECT, sodium benzoate, ginkgo biloba, and minocycline, had only one RCT with limited sample size. Conclusion: In this review, no definite effective augmentation strategy was found for clozapine-resistant patients. Some potential strategies with beneficial effects on psychopathology need further studies with a larger sample size to support their efficacy.
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