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

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

Open access
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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  • Antipsychotic medication is first line for SSD, effective for positive symptoms but limited for negative symptoms and cognitive impairment.

    “Antipsychotic medication is the first line of treatment for SSD, showing effectiveness in managing positive symptoms like hallucinations and delusions but showing limited efficacy in addressing negative symptoms and cognitive impairment.10–12”

    From Yoga-Based Group Intervention for Inpatients with Schizophrenia Spectrum Disorders—Feasibility, Acceptability, and Preliminary Outcomes of a Rater-Blinded Randomized Controlled Trial. (2026) · cites this paper as [10]

    The Summary and conclusions call antipsychotics a cornerstone of schizophrenia treatment and state that no medications are approved for cognitive impairment or negative symptoms in schizophrenia. The acute-efficacy section reports a larger effect on positive than negative symptoms, while also finding some benefit for negative symptoms. The claim extends these conclusions from schizophrenia to SSD as a whole, which the cited passages do not establish. (LLM, conf=0.82)

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Research works printed but not linked: 5

  1. A full list of the papers available in the Special Collection on Antipsychotics: Advances, Limitations, and Alternatives in Therapeutic Advances in Psychopharmacology is available at: http://journals.sagepub.com/page/tpp/special- collection/antipsychotics
  2. Kane JM, Kishimoto T and Correll CU. Factors contributing to non-adherence in patients with psychotic disorders. World Psychiatry 2013; 12: 216-226.
  3. Ackenheil M and Hippius H. Clozapine. In: Usdin E and Forrest IS (eds) Psychotherapeutic drugs: part II. New York: Marcel Dekker; 1977, pp.923-956.
  4. Kane JM and Correll CU. What is the role of clozapine in schizophrenia? JAMA Psychiatry 2016; 73: 187-188.
  5. Lieberman JA, Safferman AZ, Pollack S, et al. Clinical effects of clozapine in chronic schizophrenia: response to treatment and predictors of outcome. Am J Psychiatry 1994; 151: 1744-1752.

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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
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 · 2017: 1
FWCI
2.58
Type
journal article
Language
en
Open access
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 › 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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