Resistance is not futile: treatment-refractory schizophrenia - overview, evaluation and treatment

Schizophrenia is a debilitating condition with three main symptom domains: positive, negative, and cognitive. Approximately one-third of persons with schizophrenia will fail to respond to treatment. Growing evidence suggests that treatment-resistant (refractory) schizophrenia (TRS) may be a distinct condition from treatment-respondent schizophrenia. There is limited evidence on effective treatments for TRS, and a lack of standardized diagnostic criteria for TRS has hampered research. Areas covered: A literature search was conducted using Pubmed.gov and the EMBASE literature database. The authors discuss the pragmatic definitions of TRS and review treatments consisting of antipsychotic monotherapy and augmentation strategies. Expert opinion: Currently available first-line antipsychotic medications are generally effective at treating the positive symptoms of schizophrenia, leaving residual negative and cognitive symptoms. Before diagnosing TRS, rule out any pharmacodynamic or pharmacokinetic failures. Most evidence supports clozapine as having the most efficacy for TRS. If clozapine is used, it should be optimized, and serum levels should be at least 350-420 ng/ml. If clozapine is unable to be tolerated, some evidence suggests olanzapine at dosages up to 40mg/day can be useful. Augmentation strategies have weak evidence. Tailoring treatment to the specific domain is the preferred approach, and the use of a structured assessment/outcome measure is encouraged.