Role of antipsychotic polypharmacotherapy in the treatment of schizophrenia

Since the introduction of phenothiazines in the 1950s, clinicians have used antipsychotics in combination. This practice has previously been declared irrational as traditional antipsychotics were thought to work by similar mechanisms. However, the advent of the atypical antipsychotics provides a cadre of new medications with varying pharmacodynamic profiles. Once again, the potential use of combination antipsychotic therapy is being explored. Potential advantages of combination antipsychotics include the possibility of increased efficacy in patients with treatment-resistant symptoms, enhanced effect on agitation and positive symptoms in acutely psychotic individuals, and decreased withdrawal symptoms in patients being converted from one antipsychotic to another. Recommendations for clinical guidelines for antipsychotic combinations are limited at present by inadequate efficacy and safety data and clinical experience regarding optimal use.