Cited by 408Schizophrenia research and treatmentNeurotransmitter Receptor Influence on BehaviorTreatment of Major Depression

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Delayed-Onset Hypothesis of Antipsychotic Action: A Hypothesis Tested and Rejected

Agid, Ofer, Kapur, Shitij, Arenovich, Tamara, Zipursky, Robert B.·2003·Archives of General Psychiatry

DOI 10.1001/archpsyc.60.12.1228

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Abstract

Context To understand the mechanism of action of antipsychotic drugs, it is critical to recognize the time course over which these medications take effect. Current models of antipsychotic action presume a "delayed onset" of action. Objective To test the delayed-onset hypothesis of antipsychotic action via a meta-analytic study. Data sources and study selection Double-masked studies that reported results from active or placebo-controlled trials of antipsychotic response during the first 4 weeks of treatment were selected. These studies were identified by searching MEDLINE, 1996 to 2001; the Cumulative Index to Nursing and Allied Health, 1982 to 2001; EMBASE, 1980 to 2001; the ACP Journal Club; the Cochrane Database of Systematic Reviews; and the Database of Abstracts of Reviews of Effectiveness. Leads from these sources were followed up by manual searches. Data synthesis Forty-two published studies, including 7450 patients and 119 independent response vs time curves, were identified. Reductions in total scores on the Brief Psychiatric Rating Scale and the Positive and Negative Syndrome Scale were 13.8% during week 1, 8.1% during week 2, 4.2% during week 3, and 4.7% during week 4. This pattern of "early-onset" improvement was present even after the estimated effect of placebo treatment was removed and when results were restricted to the psychotic subscales of the scales. Conclusions This analysis rejects the commonly held hypothesis that antipsychotic response is delayed. Rathe…

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Authors: Agid, O., Kapur, S., Arenovich, T., & Zipursky, R. B.
Affiliations: Centre for Addiction and Mental Health (CA)
ORCID: Agid, Ofer
Kapur, Shitij
Zipursky, Robert B.
Venue: Archives of General Psychiatry
Publisher: American Medical Association (AMA)
Published: 2003-12-01
Volume: 60
Issue: 12
Pages: 1228
ISSN: 0003-990X (ISSN-L)
DOI: 10.1001/archpsyc.60.12.1228
OpenAlex: W2000636120
Cited by: 408
References: 86
Citations by year: 2026: 5 · 2025: 10 · 2024: 9 · 2023: 5 · 2022: 14 · 2021: 8 · 2020: 14 · 2019: 10 · 2018: 21 · 2017: 16 · 2016: 16 · 2015: 20 · 2014: 24 · 2013: 26 · 2012: 31
FWCI: 8.77
Type: journal article
Language: en
Open access: closed
Locations: Archives of General Psychiatry (publishedVersion)
PubMed (publishedVersion)
Research Portal (King's College London) (submittedVersion)
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 (medical) › Treatment of Major Depression
Keywords: antipsychotic drugs, mechanism of action, schizophrenia, Brief Psychiatric Rating Scale, PANSS, placebo response
MeSH terms: Adolescent, Adult, Aged, Double-Blind Method, Female, Humans, Male, Middle Aged, Psychiatric Status Rating Scales, Psychotic Disorders, Time Factors, Antipsychotic Agents, Treatment Outcome, Controlled Clinical Trials as Topic

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Delayed-Onset Hypothesis of Antipsychotic Action: A Hypothesis Tested and Rejected

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