Tolerability and safety outcomes of first-line oral second-generation antipsychotics in patients with schizophrenia

ABSTRACT

Introduction

Antipsychotics are the foundation of pharmacologic treatment for schizophrenia. There are many oral antipsychotics available and given that these medications are generally considered comparably efficacious when titrated to an adequate dose, their varied tolerability, and safety profiles become critically important for medication selection.

Areas covered

This paper reviews tolerability and safety considerations for first-line second-generation oral antipsychotics currently approved for the treatment of schizophrenia in the USA. Excluded from consideration are clozapine and non-oral formulations.

Expert Opinion

Among antipsychotics, there are many differences in adverse reactions observed in clinical trials, such as variable likelihood to cause sedation vs insomnia, weight gain and abnormalities in glucose/lipid metabolism, hyperprolactinemia, potential for impact on the QT interval, and motoric adverse effects. Additional safety data that can help with medication selection include safety in pregnancy and lactation, and potential for drug–drug interactions. Ultimately, working with patients to personalize treatment by focusing on safety and individual tolerability considerations for various adverse effects can help in building a therapeutic alliance and improving patients’ outcomes.

KEYWORDS:

• Medication safety
• metabolic syndrome
• movement disorders
• psychosis
• antipsychotics
• adverse events

Article highlights

• Oral antipsychotics, with the exception of clozapine, are generally considered equally effective for the treatment of schizophrenia.

• For patients early in therapy, second generations antipsychotics (SGAs) are preferred due to their lower risk of motoric adverse events, as compared to first generation antipsychotics (FGAs).

• There are many oral formulations of SGAs approved by the Food and Drug Administration for the treatment of schizophrenia, and their side effect profiles vary significantly.

• Tailoring medication selection for individual patients should include consideration of common side effects and safety concerns such as risk for weight gain and safety in pregnancy.

• Collaborating with patients to personalize medication selection can improve the therapeutic alliance and treatment outcomes.

Reviewer disclosures

Kristen Ward: Advisory board: BioXcel Therapeutics:

Leslie Citrome: Consultant: AbbVie/Allergan, Acadia, Adamas, Alkermes, Angelini, Astellas, Avanir, Axsome, Biogen, BioXcel, Boehringer Ingelheim, Cadent Therapeutics, Cerevel, Clinilabs, COMPASS, Delpor, Eisai, Enteris BioPharma, HLS Therapeutics, Idorsia, INmune Bio, Impel, Intra-Cellular Therapies, Janssen, Karuna, Lundbeck, Luye, Lyndra, MapLight, Marvin, Medavante-ProPhase, Merck, Mitsubishi-Tanabe Pharma, Neumora, Neurocrine, Neurelis, Noema, Novartis, Noven, Otsuka, Ovid, Praxis, Recordati, Relmada, Reviva, Sage, Sumitomo/Sunovion, Supernus, Teva, University of Arizona, Vanda, Wells Fargo, and one-off ad hoc consulting for individuals/entities conducting marketing, commercial, or scientific scoping research; Speaker: AbbVie/Allergan, Acadia, Alkermes, Angelini, Axsome, BioXcel, Eisai, Idorsia, Intra-Cellular Therapies, Janssen, Lundbeck, Neurocrine, Noven, Otsuka, Recordati, Sage, Sunovion, Takeda, Teva, and CME activities organized by medical education companies such as Medscape, NACCME, NEI, Vindico, and Universities and Professional Organizations/Societies; Stocks (small number of shares of common stock): Bristol-Myers Squibb, Eli Lilly, J & J, Merck, Pfizer purchased > 10 years ago, stock options: Reviva; Royalties/Publishing Income: Taylor & Francis (Editor-in-Chief, Current Medical Research and Opinion, 2022-date), Wiley (Editor-in-Chief, International Journal of Clinical Practice, through end 2019), UpToDate (reviewer), Springer Healthcare (book), Elsevier (Topic Editor, Psychiatry, Clinical Therapeutics)

Author contribution statement

L Citrome and KM Ward were both involved in conceptualization, drafting, and revision of the manuscript.

Additional information

Funding

This paper was not funded.