CNSPulse

MONDO COMBO: DO COMBINATIONS OF ANTIPSYCHOTICS EVER MAKE ANY SENSE?

Leslie Citrome — New York Medical College

2026 ASCP Annual Meeting

Treating people with schizophrenia with a combination of antipsychotic medications is common, with estimates of prevalence ranging from about 10% to 30%, with higher rates in forensic populations. Several explanations have been proffered: augmentation of clinical efficacy for treatment resistant schizophrenia (TRS), augmentation of clinical efficacy for non-TRS, addressing metabolic concerns with the antipsychotic currently being prescribed, a hoped-for fail-safe strategy when the added antipsychotic is a long-acting injectable, or, in some cases, poly-antipsychotic treatment is the result of a crosstitration that was never completed. The evidence supporting combining antipsychotics for the treatment of schizophrenia is generally weak, with the possible exception of the combination of clozapine with aripiprazole. This presentation will summarize the extant short-term and long-term literature that has examined this approach to treatment.

References

  1. Højlund M, Köhler-Forsberg O, Gregersen AT, et al. Prevalence, correlates, tolerabilityrelated outcomes, and efficacy-related outcomes of antipsychotic polypharmacy: a systematic review and meta-analysis. Lancet Psychiatry. 2024;11(12):975-989.
  2. Horvitz-Lennon M, Volya R, Zelevinsky K, et al. Significance and Factors Associated with Antipsychotic Polypharmacy Utilization Among Publicly Insured US Adults. Adm Policy Ment Health. 2022;49(1):59-70.