Drug–drug interactions involving antipsychotics and antihypertensives

ABSTRACT

Introduction

Antipsychotics represent the mainstay in the treatment of patients diagnosed with major psychiatric disorders. Hypertension, among other components of metabolic syndrome, is a common finding in these patients. For their psychiatric and physical morbidity, many patients receive polypharmacy, exposing them to the risk of clinically relevant drug–drug interactions.

Areas covered

This review summarizes the knowledge regarding the known or potential drug–drug interactions between antipsychotics and the main drug classes used in the treatment of hypertension. We aimed to provide the clinician an insight into the pharmacokinetic and pharmacodynamic interactions between these drugs for a better choice of combinations of drugs to treat both the mental illness and cardiovascular risk factors. For this, we performed a literature search in PubMed and Scopus databases, up to 31 July 2021.

Expert opinion

The main pharmacokinetic interactions between antipsychotics and antihypertensive drugs involve mainly the cytochrome P450 system. The pharmacodynamic interactions are produced by multiple mechanisms, leading to concurrent binding to the same receptors. The data available regarding drug–drug interactions is mostly based on case reports and small studies and therefore should be interpreted with caution. The current knowledge is sufficiently strong to guide clinicians in selecting safer drug combinations as summarized here.

KEYWORDS:

• Antipsychotics
• antihypertensives
• drug–drug interactions
• metabolic syndrome

Article highlights

• Antipsychotics have a potential for reducing blood pressure and associated risk for orthostatic hypotension. Therefore, close monitoring of blood pressure and adjusting the dose of antihypertensive medications is necessary.

• As first-line choices for antihypertensive treatment, probably the safest are ACEIs or ARBs, as they have little or no interference with the CYP450 system. If clozapine is used in combination with ACEIs, the white blood cell count and plasma electrolytes should be evaluated periodically.

• As a second-line medication for hypertension, a diuretic is an excellent choice, especially in combination with an ACEI/ARB for counteracting the potential elevation of potassium levels with an ACEI/ARB.

• A CCB has value as an alternative to diuretic therapy known for its low risk of adverse events. We do not recommend the use of diltiazem or verapamil due to their inhibitory effect on CYP3A4.

• BBs are less useful for the management of hypertension in patients treated with antipsychotics because of many pharmacodynamics interactions. If needed, nebivolol seems to be a safer choice in terms of interactions with antipsychotics.

This box summarizes key points contained in the article.

Declaration of interest

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. CA Buzea has been a consultant to or has received honoraria from Bayer, Boehringer-Ingelheim, Pfizer, Servier, and AstraZeneca. 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’s fees from Astellas, Dainippon Sumitomo Pharma, 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, Takeda Pharmaceutical, Tsumura, Wiley Japan, and Yoshitomi Yakuhin; and research grants from Dainippon Sumitomo Pharma, Eisa, Mochida Pharmaceutical, Meiji Seika Pharma, and Shionogi. Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.

Additional information

Funding

This paper was not funded.