Current and emerging long-acting antipsychotics for the treatment of schizophrenia

ABSTRACT

Introduction: In this review, the authors discuss the role of long-acting injectable antipsychotics (LAIs) for schizophrenia, focusing on the effectiveness and new perspectives introduced by such treatment strategy. Despite their promising pharmacokinetic features and their potential advantages in medication adherence, clinical outcomes, and medical costs, LAIs are not habitually presented as an option for patients, especially in the early phase of schizophrenia.

Areas covered: This review explores the panorama of available LAIs for the treatment of schizophrenia, first-episode of psychosis, approved indications, medical costs, medication adherence, side effects, effectiveness and differences between first-generation (FGA)-LAIs and second-generation (SGA)-LAIs.

Expert Opinion: LAIs differ in terms of specific indications, approved injection sites, needle size, injection volume, injection interval as well as potential drug–drug interactions, and commonly reported adverse reactions. The approved indications have expanded beyond schizophrenia to include bipolar and schizoaffective disorder. SGA-LAIs are often preferred to FGA-LAIs. FGA-LAIs although are less chosen in new patients due to the induction of cognitive and extrapyramidal side effects, even if, on the other hand, many SGA-LAIs are burden by hyperprolactinemia and weight gain. After a review of the available evidence, insight is provided into the potential and current therapeutic opportunities offered by LAI antipsychotic formulations.

KEYWORDS:

• Antipsychotic treatment
• depot formulation
• drug safety
• first-generation antipsychotic (fga)
• long-acting injectable (lai)
• psychopharmacology
• schizophrenia (sz)
• second-generation antipsychotic (sga)
• tolerability
• treatment management

Article highlights

• Schizophrenia is one of the top 25 major causes of disability worldwide. It is a chronic and disabling psychiatric disorder with substantial human and financial costs. Antipsychotic drugs are a milestone of current psychiatric treatment, but non-adherence is a significant problem for many patients.

• Long-term continuous antipsychotic therapy is desirable for patients with schizophrenia to control symptoms and reduces relapse rates. Long-acting injectable (LAIs) antipsychotics reduce the risk of relapse or re-hospitalization, and they eliminate the guesswork about adherence status.

• Despite the numerous and significant advantages of LAIs, they are not routinely offered as a treatment option to patients.

• LAIs offer lower adherence requirements than daily oral drugs, and more real-world observational studies have shown that patients receiving LAI therapy have a reduced risk of relapse and hospitalization.

• First-generation antipsychotics (FGA)-LAIs are burdened with numerous side effects, such as movement-related side effects and long-term cognitive impairment that limit their use, especially in first-episode or young patients.

• Second-generation antipsychotics (SGA)-LAIs such as risperidone, paliperidone palmitate at 1 or 3 months, aripiprazole at 1 or 2 months, and olanzapine pamoate provide better tolerance and less frequent adverse neurological side effects than FGA-LAI. Moreover, LAIs represent a valid option compared to oral antipsychotics also in youth and in the first-episode psychosis, where possible.

• It is desirable to consider LAIs for young patients or patients with recent-onset schizophrenia or first-episode psychosis, and those with several risk factors for poor drug adherence, such as a history of non-adherence, severe symptoms, cognitive impairment, ambivalence or negative attitudes towards drugs, and poor insight.

This box summarizes key points contained in the article.

Declaration of interest

The authors have no 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. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

A reviewer on this manuscript has received manuscript or speaker’s fees from Astellas, Dainippon Sumitomo Pharma, Eisai, Eli Lilly, Elsevier Japan, Janssen Pharmaceuticals, Kyowa Yakuhin, Meiji Seika Pharma, Mitsubishi Tanabe Pharma, MSD, Nihon Medi-Physics, Novartis, Otsuka Pharmaceutical, Shionogi, Shire, Tsumura, Wiley Japan, and Yoshitomi Yakuhin, and research grants from Eisai, Mochida Pharmaceutical, Meiji Seika Pharma and Shionogi. All other peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.