Rational polypharmacy in schizophrenia.

Approximately 10 to 30% of patients with schizophrenia show poor response to neuroleptics alone. An initial evaluative and treatment approach to these patients is outlined, and the literature on adjunctive treatments, which seek to augment neuroleptic effects, is reviewed. The greatest evidence for efficacy has been shown for lithium, benzodiazepines, carbamazepine, reserpine, and electroconvulsive therapy, although individual patients may also respond to propranolol, clonidine, valproic acid, and L-dopa. Antidepressants may also be useful for treating comorbid depression in nonacutely psychotic patients. One general theme is that no one adjunctive treatment benefits all patients; indeed, only a minority of patients responds to any given agent. Therefore, the choice of specific treatments is best guided by the clinical characteristics of the individual patient. These observations raise the possibility that subgroups of schizophrenia exist; delineation of differences in clinical response to biochemically distinct agents may help elucidate such underlying differences between patient groups.