Rational antipsychotic polypharmacy

The use of two antipsychotics for the treatment of individuals with psychiatric disorders is not uncommon in clinical practice but is rarely documented in the literature. The present article suggests an alternative method of treating individuals who show a partial but inadequate response to antipsychotic monotherapy. A rational strategy for augmenting one antipsychotic with a second, based on pharmacodynamic and pharmacokinetic principles, is provided. The present approach considers the 5-hydroxytryptamine2 to dopamine2 ratio, other complementary receptor affinities and drug-drug interactions involving the cytochrome P450 isoenzymes. The present article presents a rationale for augmenting haloperidol in patients who are partially responsive to clozapine.