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
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.