Personalized switching from oral to long-acting injectable second-generation antipsychotics in schizophrenia treatment using pharmacokinetic considerations

ABSTRACT

Introduction

Long-acting injectable (LAI) formulations of second-generation antipsychotics (SGA) are a mainstay in the treatment of schizophrenia-spectrum patients, and their use improves adherence and reduces relapse risk. Personalizing LAI-based therapy involves tailoring the transition from oral to LAIs based on individual and drug-related pharmacokinetic peculiarities.

Areas covered

We discuss pharmacokinetic considerations as a cornerstone of a smooth transition from oral to LAI SGAs based on works identified using an updated search in PubMed and Embase in February 2023. Establishing the extent of antipsychotic exposure during oral SGA-treatment from the patient’s SGA levels is often a more appropriate orientation method to choose the equivalent LAI dose than population-based data. Oral dose adjustment during LAI transition can also be guided by checking SGA levels before the LAI injection.

Expert opinion

LAI SGAs may dominate the maintenance treatment of schizophrenia-spectrum disorders with increased use for other severe mental illnesses such as bipolar disorder. Spurring this trend is the development of newer formulations with longer injection intervals and increased administration ease, but transitioning from oral SGA remains a challenge. By understanding the pharmacokinetics of LAI formulations and measuring SGA levels during oral therapy, one can personalize/optimize the switch from oral SGAs to LAI counterparts.

KEYWORDS:

• Adherence
• second-generation antipsychotics
• depot
• long-acting injectable
• pharmacokinetics
• schizophrenia
• Therapeutic drug monitoring (TDM)
• transition

Article highlights

• Given the increasingly established role of long-acting injectable (LAI) second-generation antipsychotics (SGA) in schizophrenia treatment, there is a clear need to improve transition processes from oral to LAI SGAs.

• Assessment of plasma levels for antipsychotics is currently the only well-established treatment personalization tool.

• Assessment of plasma SGA levels and their correlation with symptom improvement is helpful to determine the patient’s individual pharmacodynamic response, and their individual kinetic profile for that medication before transitioning from oral to an LAI formulation.

• Measuring plasma SGA levels can also be of substantial benefit when transitioning to SGA LAI formulations with longer injection intervals or different administration routes, to ensure comparable maintenance antipsychotic exposure.

• The regular assessment of plasma SGA levels to improve transition from oral to LAI SGAs may help addressing safety concerns with regard to treatment with LAI SGAs, which are underprescribed.

• Future research will need to generate more robust evidence on plasma SGA levels for novel LAI formulations.

Declaration of interest

G. Schoretsanitis served as a consultant for HLS Therapeutics and Thermo Fisher. J. M. Meyer has served as a speaker or advisor for Acadia Pharmaceuticals, Alkermes, Inc., Intra-Cellular Therapies, Karuna, Neurocrine, Noven, Otsuka America, Inc., and Sunovion Pharmaceuticals. C. Hiemke served as a speaker for 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.

Supplementary Material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/17425255.2023.2220962

Additional information

Funding

This paper was not funded.