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

ABSTRACT

Introduction

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.

Areas covered

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.

Expert opinion

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.

KEYWORDS:

• Antipsychotics
• lipid-lowering
• hypoglycemics
• weight loss agents
• drug–drug interactions

Article highlights

• Patients with severe mental illness frequently have one or more of the components of metabolic syndrome. Moreover, many antipsychotics have an unfavorable effect on glucose metabolism, lipid profile, or body weight.

• For treating dyslipidemia, the first choice is statin therapy, favoring rosuvastatin, fluvastatin, or pravastatin for less interaction with the cytochrome P450 system involved in the metabolism of antipsychotics.

• In patients with diabetes, metformin remains the first-line drug, while GLP-1 receptor agonists represent an alternative. The emerging SGLT2 inhibitors may be used, but more data regarding drug–drug interactions is required.

• For reversal or attenuation of antipsychotic-induced weight gain or in obese patients, metformin, liraglutide, and semaglutide may be safely recommended.

This box summarizes key points contained in the article.

Declaration of interest

CA Buzea has been a consultant to or has received honoraria from Bayer, Boehringer-Ingelheim, Pfizer, and Servier. CU Correll has been a consultant and/or advisor to or has received honoraria from AbbVie, Acadia, Alkermes, Allergan, Angelini, Aristo, Axsome, Boehringer-Ingelheim, Cardio Diagnostics, Cerevel, CNX Therapeutics, Compass Pathways, Damitsa, Gedeon Richter, Hikma, Holmusk, IntraCellular Therapies, Janssen/J&J, Karuna, LB Pharma, Lundbeck, MedAvante-ProPhase, MedInCell, Medscape, Merck, Mindpax, Mitsubishi Tanabe Pharma, Mylan, Neurocrine, Noven, Otsuka, Pfizer, Pharmabrain, PPD Biotech, Recordati, Relmada, Reviva, Rovi, Seqirus, Servier, SK Life Science, Sumitomo Dainippon, Sunovion, Sun Pharma, Supernus, Takeda, Teva, and Viatris. He provided expert testimony for Janssen and Otsuka. He served on a Data Safety Monitoring Board for Lundbeck, Relmada, Reviva, Rovi, and Teva. He has received grant support from Janssen and Takeda. He received royalties from UpToDate and is also a stock option holder of Cardio Diagnostics, Mindpax, and LB Pharma. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

A reviewer on this manuscript has disclosed receiving manuscript or speaker fees from Astellas, Eisai, Eli Lilly, Elsevier Japan, Janssen Pharmaceuticals, Kyowa Yakuhin, Lundbeck Japan, Meiji Seika Pharma, Mitsubishi Tanabe Pharma, MSD, Nihon Medi-Physics, Novartis, Otsuka Pharmaceutical, Shionogi, Shire, Sumitomo Pharma, Takeda Pharmaceutical, Tsumura, Viatris, Wiley Japan, and Yoshitomi Yakuhin; and research grants from Eisai, Mochida Pharmaceutical, Meiji Seika Pharma, Shionogi, and Sumitomo Pharma. Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.

Additional information

Funding

This paper was not funded.