Polypharmacy With Second-Generation Antipsychotics: A Review of Evidence

Abstract

The objective of this study was to review the prevalence of polypharmacy with second-generation antipsychotics (SGAs) in clinical practice, pharmacological reasons for such practice, and the evidence for and against such polypharmacy. Clinical trial reports, case reports, and reviews were identified by a PubMed literature search from 1966 through October 2006, with retrieved publications queried for additional references. We excluded reports on augmentation with non-antipsychotic medications and polypharmacy involving combinations of SGAs and first-generation (conventional) antipsychotics (FGAs) or combinations of two FGAs. We identified 75 reports concerning SGA polypharmacy, from which we extracted data on study design, sample size, medications, rating scales, outcome, and conclusions. Data from randomized controlled trials and larger case series are presented in detail and case reports are briefly discussed. Polypharmacy with SGAs is not uncommon, with prevalence varying widely (3.9% to 50%) depending on setting and patient population, despite limited support from blinded, randomized, controlled trials or case reports that employed an A-B-A (monotherapy-combination therapy-monotherapy) design and adequate dosing and duration of treatment. Rather than prohibiting or discouraging co-prescription of SGAs, needs of patients and clinicians should be addressed through evidence-based algorithms. Based on unmet clinical needs and modest evidence from case reports, combinations of two SGAs may merit future investigation in efficacy trials involving patients with schizophrenia who have treatment-resistant illness (including partial response) or who are responsive to treatment but develop intolerable adverse effects. Other areas that may merit future research are efficacy of SGA polypharmacy for schizophrenia accompanied by comorbid conditions (eg, anxiety, suicidal or self-injurious behavior, aggression) and for reducing length of stay in acute care settings.