In three recent prescription surveys, up to 25% of patients with psychiatric were prescribed two or more antipsychotics concurrently . Despite the prevalence of antipsychotic polypharmacy in clinical practice, clinical evidence in this area is limited . The lack of both evidence-based data and theoretical models of antipsychotic combination therapy implies that physicians rely on clinical experience and anecdotal case reports in the design of polypharmacy treatment protocols. This task is enormous when one recognizes the subtle differences in distinguishing the numerous antipsychotics in addition to the probable heterogeneous etiology of schizophrenia . Rather than have clinicians rely on intuition to discern pathophysiologically distinct illnesses that may have identical syndromal profiles, it is appropriate to design a rational theoretical basis for combination antipsychotic therapy.
In every situation where a supplementary medication is added to a treatment regimen, the likelihood of problematic pharmacodynamic and/or pharmacokinetic concerns increases. Therefore, in the absence of evidence-based antipsychotic polypharmacy data, it is rational to only combine antipsychotics in special circumstances. Based on this principle, one possible strategy may be to limit antipsychotic polypharmacy to an augmentation scenario. In this case, a second antipsychotic may be added to the treatment regimen of an individual that displays only partial response to the primary antipsychotic. Thus, rather than discontinue a somewhat effective medication trial, the addition of a second antipsychotic may be warranted.