Introduction: Although clozapine (CLZ) is considered the best evidence-based therapeutic option for treatment of resistant schizophrenia patients, a significant proportion of CLZ-treated patients show a partial or inadequate response to treatment, leading to increased healthcare cost and poor quality of life for affected individuals.
Areas covered: This paper comprises a review of main research in CLZ augmentation strategies for treatment-refractory schizophrenia, with a focus on research conducted between 1990 and 2014. Databases that were searched include: PubMed, CINAHL, EMBASE PsychINFO, AgeLine and Cochrane Database of Systematic Reviews. Primary search terms were 'clozapine augmentation', 'clozapine and add-on' and 'treatment-resistant schizophrenia', with cross reference to specific agents covered in this article. We reviewed the available evidence on CLZ augmentation with antipsychotics, antidepressants, mood stabilizers and other agents.
Expert opinion: Many drugs have been evaluated as CLZ add-on therapies without demonstrating convincing efficacy in treating refractory schizophrenia symptoms. More research is needed to better define outcomes in schizophrenia, the topic of treatment-resistance and more well-designed trials are required to establish true efficacy and safety of CLZ augmentation strategies.
Keywords: add-on; clozapine augmentation; refractory; treatment-resistant schizophrenia.