Clozapine augmentation: safety and efficacy

While clozapine has been demonstrated to be effica-cious in refractory schizophrenia and possibly schizoaffective as well as bipolar disorders, a substan-tial number of patients still remain unresponsive. One strategy in treating these refractory patients is to aug-ment clozapine with other somatic treatments. This article reviews the efficacy and safety of the combina-tion of clozapine with other somatic treatments. A total of 70 articles were obtained from a manual, as well as computerized (Medline), search of the English lan-guage literature from 1978 to March 1998. Few con-trolled studies exist; most were case reports/series. From these data, the greatest risk of adverse effects seems to be associated with clozapine combined with benzodiazepines, valproate, or lithium, but no cur-rently evaluated combination is absolutely unsafe. In terms of efficacy, the data suggest a number of poten-tial augmentation strategies, although controlled data are few. Combination therapies with clozapine are common in clinical practice, despite a lack of empiri-cal data, and the benefits and risks of these combina-tions need to be systematically reviewed