Comorbidities and the right dose: antipsychotics

ABSTRACT

Introduction

The effects of antipsychotic drugs are dose-dependent, which is particularly true for their efficacy, each antipsychotic having a specific dose–response curve. This may justify individualizing doses for these agents.

Areas covered

We review the pharmacokinetic profiles of seven oral antipsychotics: haloperidol, risperidone, olanzapine, clozapine, quetiapine, ziprasidone, and aripiprazole. Their main indications are psychotic and affective disorders. They are prescribed in a very large population which may have comorbidities. Hence, we analyze the impact of the latter on the pharmacokinetic profiles of these antipsychotics, focusing on renal and hepatic impairment. Reviews and clinical trials were discussed based on a systematic literature search (PubMed) ranging from 1995 to 2022.

Expert opinion

Factors liable to impact antipsychotic dosage are numerous and their subsequent effects often hard to predict, due to multilevel interactions and compensatory phenomena. In clinical practice, physicians must be aware of these potential effects, but base their decisions on monitoring antipsychotic plasma levels.

KEYWORDS:

• Antipsychotics
• pharmacokinetics
• dosage individualization
• comorbidity
• cytochrome P450

Article highlights

• Each antipsychotic has a specific dose–response curve.

• Main comorbidities impacting antipsychotic dose adjustment are renal and hepatic impairment, and substance use disorders.

• Among antipsychotics, aripiprazole and ziprasidone are those requiring the least dose adjustment, when prescribed to patients with comorbid conditions.

• The resulting impact of comorbidities and polypharmacy on the pharmacokinetics of antipsychotics is difficult to predict in clinical practice.

• Plasma concentrations of antipsychotics could predict clinical response better than their doses.

This box summarizes key points contained in the article.

Declaration of interest

N Simon has received honoraria from Lundbeck, Otsuka, and Ethypharm. J-M Azorin has received honoraria from Lundbeck and Otsuka. 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

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.