"Prescribers Beware": a narrative review of dangerous drug-drug-interactions involving psychotropic medications.

PURPOSE: Polypharmacy has long been a concern in the psychiatric patient population and carries significant mortality implications across clinical settings. The percentage of outpatient psychiatric patients with two or more psychotropic medications prescribed is rising, with the mean number of drugs being prescribed during hospitalization being as high as 6.1, and over half of patients receiving more than one psychotropic drug. Yet no compilation of dangerous and lethal drug interactions involving psychotropic medications exist to date to guide clinical medication review. This study addresses this gap by providing a resource to help clinicians identify and avoid high-risk polypharmacy interactions. METHODS: We conducted a targeted literature review of potentially fatal or irreversible drug-drug interactions involving commonly prescribed psychotropic medications. PubMed Central (PMC) studies published from 1973 to the present were queried. A total of 566 relevant articles were screened, of which 36 were reviewed in detail and incorporated. RESULTS: Five potentially fatal drug interactions with clear and preventable safety risks were identified, consisting of: clozapine & fluvoxamine, "the holy trinity", Monoamine oxidase inhibitors (MAOIs) & meperidine, lithium and thiazide diuretics, and lithium with haloperidol. Current evidence supporting these associations, their presentation, proposed mechanism of the adverse interaction, as well as available treatments if any are detailed. CONCLUSIONS: This review highlights specific drug-drug interaction combinations that are well supported by the literature and clinically actionable to avoid, helping clinicians recognize and prevent dangerous polypharmacy combinations during everyday clinical practice.