Cited by 259Schizophrenia research and treatmentMental Health and PsychiatryTreatment of Major Depression

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The acute efficacy of antipsychotics in schizophrenia: a review of recent meta-analyses

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Haddad, Peter M., Correll, Christoph U.·2018·Therapeutic Advances in Psychopharmacology

DOI 10.1177/2045125318781475PMC PMC6180374

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Abstract

Schizophrenia is the eighth leading cause of disability worldwide in people aged 15–44 years. Before antidopaminergic antipsychotics were introduced in the 1950s, no effective medications existed for the treatment of schizophrenia. This review summarizes key meta-analytic findings regarding antipsychotic efficacy in the acute treatment of schizophrenia, including clozapine in treatment-resistant patients. In the most comprehensive meta-analysis of randomized controlled trials conducted in multi-episode schizophrenia, antipsychotics outperformed placebo regarding total symptoms, positive symptoms, negative symptoms, depressive symptoms, quality of life and social functioning. Amongst these outcomes, the standardized mean difference for overall symptoms was largest, that is, 0.47 (95% credible interval = 0.42–0.51), approaching a medium effect size, being reduced to 0.38 when publication bias and small-trial effects were accounted for. A comparison of two meta-analyses indicated that first-episode patients, compared with multi-episode patients, were more likely to have at least minimal treatment response [⩾20% Positive and Negative Syndrome Scale (PANSS)/Brief Psychiatric Rating Scale (BPRS) score reduction: 81% versus 51%] and good response (⩾50% PANSS/BPRS score reduction: 52% versus 23%). In multi-episode schizophrenia, no response or worsening after 2 weeks of a therapeutic antipsychotic dose was highly predictive of not achieving a good response at endpoint (median treatment = 6 weeks: specificity = 86%; positive predictive value = 90%), suggesting a change in treatment should be considered in such cases. In first-episode psychosis, adequately dosed antipsychotic treatment trials for more than 2 weeks are recommended before using no response or worsening as a decision point for aborting a given antipsychotic. In clearly defined treatment-resistant schizophrenia, clozapine generally outperformed other antipsychotics, especially when dosed appropriately (target = 3–6 months’ duration; trough clozapine level ⩾350–400 μg/L) with a response rate (⩾20% PANSS/BPRS) of 33% by 3 months of treatment. High antipsychotic doses and psychotropic combinations are unlikely to be superior to standard doses of antipsychotic monotherapy. Acute antipsychotic efficacy in schizophrenia depends on the targeted symptom domain (greater efficacy: total and positive symptoms, lesser efficacy: negative symptoms, depressive symptoms, social functioning and quality of life). Greater antipsychotic efficacy is associated with higher total baseline symptom severity, treatment-naïveté/first-episode status, shorter illness duration, and trials that are nonindustry sponsored and that have a lower placebo effect. The heterogeneity of antipsychotic response across individuals and key symptom domains, the considerable degree of nonresponse/treatment resistance in multi-episode patients, and the adverse effect potential of antipsychotics are major limitations, underscoring the need to develop new medications for the treatment of schizophrenia. Drug development should include matching patient subgroups, which are identified by means of clinical and biomarker variables, to mechanisms of action of novel medications, targeting specific symptom domains, and investigating mechanisms of action other than dopaminergic blockade.

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Authors: Haddad, P. M., & Correll, C. U.
Affiliations: University of Manchester (GB)
Hofstra University (US)
Corresponding author: Haddad, Peter M.
ORCID: Haddad, Peter M.
Correll, Christoph U.
Venue: Therapeutic Advances in Psychopharmacology
Publisher: SAGE Publications
Published: 2018-10-08
Volume: 8
Issue: 11
Pages: 303-318
ISSN: 2045-1253 (ISSN-L)
2045-1261
DOI: 10.1177/2045125318781475
PMC: PMC6180374
OpenAlex: W2897156727
Cited by: 259
References: 74
Citations by year: 2026: 31 · 2025: 36 · 2024: 45 · 2023: 46 · 2022: 31 · 2021: 33 · 2020: 23 · 2019: 12
FWCI: 2.58
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: journals.sagepub.com/page/policies/text-and-data-mining-license (tdm)
Locations: Therapeutic Advances in Psychopharmacology (publishedVersion)
Europe PMC (PubMed Central) (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
Social Sciences › Arts and Humanities › Philosophy › Mental Health and Psychiatry
Health Sciences › Medicine › Pharmacology (medical) › Treatment of Major Depression
Keywords: schizophrenia, antipsychotic drugs, clozapine, treatment-resistant schizophrenia, first-episode psychosis, treatment response prediction, antipsychotic dosing, antipsychotic monotherapy, positive symptoms, negative symptoms, depressive symptoms, quality of life, social functioning, publication bias

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The acute efficacy of antipsychotics in schizophrenia: a review of recent meta-analyses

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