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Review
. 2023 Jun;46(2):261-275.
doi: 10.1016/j.psc.2023.02.012. Epub 2023 Mar 25.

Pharmacotherapy for Treatment-Resistant Depression: Antidepressants and Atypical Antipsychotics

Collin Vas  1 , Ayush Jain  2 , Mili Trivedi  3 , Manish Kumar Jha  4 , Sanjay J Mathew  5
Affiliations
Review

Pharmacotherapy for Treatment-Resistant Depression: Antidepressants and Atypical Antipsychotics

Collin Vas et al. Psychiatr Clin North Am. 2023 Jun.

Abstract

Treatment-resistant depression (TRD) affects one in three patients with major depressive disorder and is associated with increased risk of all-cause mortality. Studies of real-world practices suggest that antidepressant monotherapy continues to be the most widely used treatment after inadequate response to a first-line treatment. However, rates of remission with antidepressants in TRD are suboptimal. Atypical antipsychotics are the most widely studied augmentation agent and aripiprazole, brexpiprazole, cariprazine, quetiapine extended-release, and olanzapine-fluoxetine combination are approved for depression. Benefits of using atypical antipsychotics for TRD has to be weighted against their potential adverse events, such as weight gain, akathisia, and tardive dyskinesia.

Keywords: Antidepressants; Aripiprazole; Atypical antipsychotics; Brexpiprazole; Cariprazine; Major depressive disorder; Quetiapine; Treatment-resistant depression.

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Conflict of interest statement

Disclosure Dr C. Vas, A. Jain, and M. Trivedi have no conflicts to disclose. Dr M.K. Jha has received contract research grants from Acadia Pharmaceuticals, Neurocrine Bioscience, Navitor/Supernus and Janssen Research & Development; educational grant to serve as Section Editor of the Psychiatry & Behavioral Health Learning Network; consultant fees from Eleusis Therapeutics US, Inc, Janssen Global Services, Janssen Scientific Affairs, Worldwide Clinical Trials/Eliem and Inversargo, Boehringer Ingelheim, and Guidepoint Global; and honoraria from North American Center for Continuing Medical Education, Medscape/WebMD, Clinical Care Options, and Global Medical Education. Dr S.J. Mathew has served as a consultant to Allergan, Alkermes, Almatica Pharma, Axsome Therapeutics, Biohaven, BioXcel Therapeutics, Clexio Biosciences, COMPASS Pathways, Delix Therapeutics, Eleusis, EMA Wellness, Engrail Therapeutics, Greenwich Biosciences, Intra-Cellular Therapies, Janssen, Levo Therapeutics, Perception Neurosciences, Praxis Precision Medicines, Neumora, Neurocrine, Relmada Therapeutics, Sage Therapeutics, Seelos Therapeutics, Signant Health, and Sunovion; and received research support from Biohaven Pharmaceuticals, Boehringer Ingelheim, Janssen, Merck, Neurocrine, Sage Therapeutics, and Vistagen Therapeutics.

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