Receptor-Binding Profiles of Antipsychotics: Clinical Strategies When Switching Between Agents

In spite of apparent improvements in the pharmacotherapy of schizophrenia, many patients still demonstrate an incomplete therapeutic response to antipsychotic medication and/or intolerable adverse effects, necessitating a change in their medication regimen. The switch from one antipsychotic to another, however, is not without challenges and can be complicated by withdrawal-emergent adverse effects that prompt the patient or the clinician to abort the switch. The extent to which these adverse events can be predicted by comparing the effects of the old and new antipsychotic medications on various receptor systems, including dopaminergic, muscarinic, and histaminergic receptors, is of considerable clinical and research interest. For example, patients receiving a sedating antipsychotic with high affinity for histamine H₁ receptors could experience rebound insomnia if switched to a less sedating agent with a low affinity for H₁ receptors. An understanding of the differential receptorbinding profiles of the various antipsychotics can help clinicians anticipate and manage potential clinical issues that may be encountered when switching antipsychotic therapy.