Clozapine augmentation: Safety and efficacy

While clozapine has been demonstrated to be efficacious in refractory schiz ophrenia and possibly schizoaffective as well as bipolar disorders, a subst antial number of patients still remain unresponsive. One strategy in treati ng these refractory patients is to augment clozapine with other somatic tre atments. This article reviews the efficacy and safety of the combination of clozapine with other somatic treatments. A total of 70 articles mere obtai ned from a manual, as well as computerized (Medline), search of the English language literature from 1978 to March 1998, Few controlled studies exist; most mere case reports/series. From these data, the greatest risk of adver se effects seems to be associated with clozapine combined with benzodiazepi nes, valproate, or lithium, but no currently evaluated combination is absol utely unsafe. In terms of efficacy, the data suggest a number of potential augmentation strategies, although controlled data are few. Combination ther apies with clozapine are common in clinical practice, despite a lack of emp irical data, and the benefits and risks of these combinations need to be sy stematically reviewed.