Treatments for schizophrenia: a critical review of pharmacology and mechanisms of action of antipsychotic drugs
Abstract
The treatment of schizophrenia has evolved over the past half century primarily in the context of antipsychotic drug development. Although there has been significant progress resulting in the availability and use of numerous medications, these reflect three basic classes of medications (conventional (typical), atypical and dopamine partial agonist antipsychotics) all of which, despite working by varying mechanisms of actions, act principally on dopamine systems. Many of the second-generation (atypical and dopamine partial agonist) antipsychotics are believed to offer advantages over first-generation agents in the treatment for schizophrenia. However, the pharmacological properties that confer the different therapeutic effects of the new generation of antipsychotic drugs have remained elusive, and certain side effects can still impact patient health and quality of life. Moreover, the efficacy of antipsychotic drugs is limited prompting the clinical use of adjunctive pharmacy to augment the effects of treatment. In addition, the search for novel and nondopaminergic antipsychotic drugs has not been successful to date, though numerous development strategies continue to be pursued, guided by various pathophysiologic hypotheses. This article provides a brief review and critique of the current therapeutic armamentarium for treating schizophrenia and drug development strategies and theories of mechanisms of action of antipsychotics, and focuses on novel targets for therapeutic agents for future drug development.
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ADHD is not unique in this regard; many psychiatric disorders present with similar heterogeneity that arises from a complexity of neurological dysfunction not clearly directly related to current treatments.
“Indeed it should be pointed out that ADHD is not unique in this regard. Many psychiatric disorders present with similar heterogeneity that arises from a complexity of neurological dysfunction not clearly directly related to current treatments (e.g. schizophrenia [74]).”
From Linking ADHD to the Neural Circuitry of Attention (2017) · cites this paper as [74]
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- Authors
- Miyamoto, S., Duncan, G. E., Marx, C. E., & Lieberman, J. A.
- Affiliations
- St. Marianna University School of Medicine (JP)
- University of North Carolina at Chapel Hill (US)
- Duke Medical Center (US)
- Corresponding author
- Lieberman, J A
- Venue
- Molecular Psychiatry
- Published
- 2004-08-03
- Volume
- 10
- Issue
- 1
- Pages
- 79-104
- ISSN
- 1359-4184 (ISSN-L)
- 1476-5578
- OpenAlex
- W2132980997
- Cited by
- 988
- References
- 393
- Citations by year
- 2026: 23 · 2025: 25 · 2024: 32 · 2023: 40 · 2022: 37 · 2021: 40 · 2020: 45 · 2019: 42 · 2018: 40 · 2017: 41 · 2016: 54 · 2015: 52 · 2014: 46 · 2013: 72 · 2012: 66
- FWCI
- 4.72
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Molecular Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Mental Health (MH064065, P50MH064065)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Keywords
- schizophrenia, antipsychotic drugs, dopamine D2 receptor, atypical antipsychotics, partial dopamine agonist, typical antipsychotics, mechanism of action, antipsychotic adverse effects, adjunctive pharmacotherapy, antipsychotic drug development, schizophrenia pathophysiology
- MeSH terms
- Behavioral Symptoms, Humans, Schizophrenia, Antipsychotic Agents, Drug Design, Dopamine Agents, Receptors, Dopamine D2, Receptors, Glutamate, Excitatory Amino Acid Agents
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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