Antipsychotic polypharmacy or monotherapy?

The concurrent use of more than one drug to treat syndromes and diseases is common in medicine as well as in psychiatry. Despite strong recommendation by experts to employ monotherapy whenever possible, the prevalence of antipsychotic polypharmacy (APP) has greatly increased, particularly since the advent of the Second Generation Antipsychotics (SGA). The literature which consists of three RCTs, several naturalistic cohort studies and numerous case reports does not show convincing evidence of APP efficacy. The best results were seen in studies of augmentation of clozapine response by a second antipsychotic. Studies which examined the side effect burden showed higher rates of anticholinergic and extrapyramidal side effects of APP compared to monotherapy, but these differences tended to disappear when total dosage was controlled for. The relative cost of APP may be higher than monotherapy, but very little data are available. Experts recommend APP in a few special clinical situations: (a) for augmentation when a patient fails to respond to adequate antipsychotic trials, especially with clozapine; (b) in some instances of failed cross-taper of antipsychotics; (c) adding a FGA to a SGA for agitation during acute treatment of psychosis. Indiscriminate condemnation of APP is misdirected, the real culprit being incompetent pharmacotherapy. Improved education and advances in the science of psychopharmacology will lead to more specific antipsychotic therapies and ultimately to less need for APP.