Switching to long-acting injectable antipsychotics: pharmacological considerations and practical approaches

ABSTRACT

Introduction

Long-acting injectable antipsychotics (LAIs) are an effective, but potentially underutilized treatment option in schizophrenia and other severe mental illnesses. Prescribing information typically focuses on how to initiate treatment from the corresponding oral formulations. However, in clinical practice other scenarios, such as switching from other oral antipsychotics or other LAIs, occur frequently, requiring guidance.

Areas covered

Pharmacodynamic properties of antipsychotics and their relation to rebound symptoms. Pharmacokinetic properties of LAIs and their implications for switching approaches. Specific approaches to switching to LAIs.

Expert opinion

The LAI landscape has evolved significantly in the last decade with more formulations available, longer dosing intervals, and extended indications. However, currently available LAIs have various shortcomings, e.g. short dosing intervals, need for oral supplementation, loading regimens, deep intramuscular injection and/or restricted indications. Recent improvements include a one-day initiation option for aripiprazole lauroxil, aripiprazole monohydrate once-monthly, risperidone in situ microparticles and subcutaneous risperidone. Future LAI developments should focus on longer dosing intervals, subcutaneous administration, expansion of LAIs beyond currently available antipsychotic agents and indications beyond schizophrenia and bipolar disorder. In the future, LAIs might become a first-line treatment after initial oral stabilization for chronic mental disorders with need for maintenance treatment and presence of significant non-adherence.

KEYWORDS:

• Antipsychotic
• aripiprazole
• fluphenazine
• haloperidol
• olanzapine
• paliperidone
• risperidone
• schizophrenia

Article highlights

• The selection of long-acting injectable antipsychotics (LAIs), including expansion of dose intervals, initiation strategies, and subcutaneous formulations, has increased significantly in the last 5–10 years.

• Despite increasing utilization of LAIs, they are still underutilized, but data indicate acceptability of LAIs by patients when treatment providers are trained and/or offer LAIs focusing on all aspects of the LAI benefits.

• Oral supplementation or loading regimens are still necessary for some LAIs to achieve sufficient plasma levels during the first weeks of treatment, but several recently approved LAIs do not require loading strategies, booster injections, or oral supplementation.

• Discontinuation strategies of previous antipsychotic treatment depend on the differences between antidopaminergic, antihistaminergic, or anticholinergic properties of both the pre- and post-switch antipsychotic.

• Most LAIs can be initiated from the corresponding or other oral antipsychotics, as well as from other LAIs.

• Switching strategies differ based on the pharmacokinetic and pharmacodynamic properties of each individual LAI and are described in detail for all approved LAIs.

• New developments in LAIs include longer dosing intervals and the elimination of the need for loading regimens, booster injections, or oral supplementation as well as subcutaneous formulations.

• LAI formulations of additional antipsychotics are needed, including a version of olanzapine without risk of post-injection delirium/sedation syndrome well as subcutaneous formulations, with some being already in development.

Declaration of interest

M Højlund has been consultant or has received honoraria: H. Lundbeck, The Lundbeck Foundation and Otsuka.

C U Correll has been a consultant and/or advisor to or have received honoraria from: AbbVie, Acadia, Alkermes, Allergan, Angelini, Aristo, Boehringer-Ingelheim, Cardio Diagnostics, Cerevel, CNX Therapeutics, Compass Pathways, Darnitsa, Gedeon Richter, Hikma, Holmusk, IntraCellular Therapies, Janssen/J&J, Karuna, LB Pharma, Lundbeck, MedAvante-ProPhase, MedInCell, Merck, Mindpax, Mitsubishi Tanabe Pharma, Mylan, Neurocrine, Newron, Noven, Novo Nordisk,Otsuka, Pharmabrain, PPD Biotech, Recordati, Relmada, Reviva, Rovi, Seqirus, SK Life Science, 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 Compass, Lundbeck, Relmada, Reviva, Rovi, Supernus, 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, LB Pharma and Quantic.

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.