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Cited by 41Schizophrenia research and treatmentMental Health and PsychiatryTreatment of Major Depression

Maximizing response to first-line antipsychotics in schizophrenia: a review focused on finding from meta-analysis

Smith, Robert C., Leucht, Stefan, Davis, John M.·2019·Psychopharmacology
DOI 10.1007/s00213-018-5133-z
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Abstract

Rationale There are many psychotropic drugs available for treatment of schizophrenia. The clinician's choice of the most effective first-line antipsychotic treatment for patients with schizophrenia should balance considerations of differential efficacy of antipsychotics against the relative risk of different side effects.Method We reviewed recent studies using meta-analytic techniques and additional studies of new antipsychotics which quantitatively evaluate the efficacy of side effects of first- and second-generation antipsychotics and studies of the efficacy on add-on secondary medications. We present an integrated summary of these results to guide a clinician's decision-making.Results Recent meta-analyses have suggested that antipsychotics are not equivalent in efficacy. Clozapine (effect size [SMD] 0.88 vs. placebo), amisulpride (effect size 0.6 vs placebo), olanzapine (effect size 0.59 vs. placebo), and risperidone (effect size 0.56 vs placebo) show small but statistically significant differences compared to a number of other antipsychotics on measures of overall efficacy (effect sizes 0.33-0.50). However, increasing placebo response remains a concern in interpreting these data. Amisulpride (effect size 0.47 vs placebo) and cariprazine (effect size in one trial compared to risperidone 0.29) have the strongest evidence indicating greater efficacy for treating primary negative symptoms relative to other antipsychotics. In terms of side effects, clozapine and olanzapine have among the highest weight gain potential and sertindole and amisulpride have more effects on QTc prolongation than other commonly used antipsychotics. Prolactin elevation is highest with paliperidone, risperidone, and amisulpride. Adjunctive treatment with an antidepressant drug may improve response in patients with schizophrenia who also have severe depressive or negative symptoms. For multi-episode patients with an inadequate response to an adequate dose and duration of the initial antipsychotic choice, switching to another antipsychotic, with a different receptor profile, may improve response, although evidence is very limited. In first-episode patients, a recent study on switching to another antipsychotic, with a different receptor profile after 4 weeks demonstrated no beneficial effects. There is little evidence to support using doses above the therapeutic range other than in exceptional circumstances.Conclusions Our review of recent studies using meta-analytic techniques has provided evidence that all antipsychotics are not equal in the severity of different side effects and in some measures of clinical efficacy. Comparative analysis and rankings from network meta-analyses can provide guidance to clinicians in choosing the most appropriate antipsychotic for first-line treatment, if used in conjunction with available information of the patient's history of previous clinical response or higher risks for specific side effects.

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Crossref · 10.1007/s00213-018-5133-z

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  • LAIs have more restrictive dose limitations than oral treatments; however, high-dose LAI treatment has not been shown to be superior to LAI treatment at doses within the identified therapeutic range.

    “Also, LAIs have more restrictive dose limitations than oral treatments; however, high-dose LAI treatment has not been shown to be superior to LAI treatment at doses within the identified therapeutic range [106–108].”

    From Pharmacokinetic Characteristics of Long-Acting Injectable Antipsychotics for Schizophrenia: An Overview (2021) · cites this paper as [108]

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Authors
Smith, R. C., Leucht, S., & Davis, J. M.
Affiliations
  • Nathan Kline Institute for Psychiatric Research (US)
  • Technical University of Munich (DE)
  • Johns Hopkins University (US)
Corresponding author
Smith, Robert C.
ORCID
Venue
Psychopharmacology
Publisher
Springer Science and Business Media LLC
Published
2018-11-30
Volume
236
Issue
2
Pages
545-559
ISSN
  • 0033-3158 (ISSN-L)
  • 1432-2072
DOI
10.1007/s00213-018-5133-z
OpenAlex
W2902252387
Cited by
41
References
72
Citations by year
2025: 2 · 2024: 5 · 2023: 6 · 2022: 7 · 2021: 11 · 2020: 9 · 2017: 1
FWCI
0.77
Type
journal article
Language
en
Open access
closed
Licence
www.springer.com/tdm (tdm)
Locations
  • Psychopharmacology (publishedVersion)
  • PubMed (publishedVersion)
  • mediaTUM – the media and publications repository of the Technical University Munich (Technical University Munich) (submittedVersion)
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 efficacy, antipsychotic adverse effects, clozapine, amisulpride, olanzapine, risperidone, cariprazine, weight gain, QTc prolongation, prolactin elevation, negative symptoms, depressive symptoms, antipsychotic switching
MeSH terms
Olanzapine, Amisulpride, Antidepressive Agents, Clozapine, Depression, Humans, Imidazoles, Indoles, Piperazines, Schizophrenia, Schizophrenic Psychology, Antipsychotic Agents, Treatment Outcome, Risperidone

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