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Patients with severe mental illness (SMI) have a high risk for diabetes, dyslipidemia, and other components of metabolic syndrome. Patients with these metabolic comorbidities and cardiac risk factors should receive not only antipsychotics but also medications aiming to reduce cardiovascular risk. Therefore, many patients may be exposed to clinically relevant drug–drug interactions. This narrative review summarizes data regarding the known or potential drug–drug interactions between antipsychotics and medications treating metabolic syndrome components, except for hypertension, which has been summarized elsewhere. A literature search in PubMed and Scopus up to 7/31/2021 was performed regarding interactions between antipsychotics and drugs used to treat metabolic syndrome components, aiming to inform clinicians’ choice of medication for patients with SMI and cardiometabolic risk factors in need of pharmacologic interventions. The cytochrome P450 system and, to a lesser extent, the P-glycoprotein transporter is involved in the pharmacokinetic interactions between antipsychotics and some statins or saxagliptin. Regarding pharmacodynamic interactions, the available information is based mostly on small studies, and for newer classes, like PCSK9 inhibitors or SGLT2 inhibitors, data are still lacking. However, there is sufficient information to guide clinicians in the process of selecting safer antipsychotic-cardiometabolic risk reduction drug combinations.

Drug–drug interactions involving combinations of antipsychotic agents with antidiabetic, lipid-lowering, and weight loss drugs