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

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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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Authors and Affiliations

  1. Department of Psychiatry, New York University School of Medicine, New York, NY, USA

    Robert C. Smith

  2. Nathan Kline Institute for Psychiatric Research, Orangeburg, NY, USA

    Robert C. Smith

  3. Department of Psychiatry and Psychotherapy, Technische Universität München, Munich, Germany

    Stefan Leucht

  4. Department of Psychiatry, College of Medicine, University of Illinois at Chicago, Chicago, IL, USA

    John M. Davis

  5. Johns Hopkins University School of Medicine, Baltimore, MD, USA

    John M. Davis

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Smith, R.C., Leucht, S. & Davis, J.M. Maximizing response to first-line antipsychotics in schizophrenia: a review focused on finding from meta-analysis. Psychopharmacology 236, 545–559 (2019). https://doi.org/10.1007/s00213-018-5133-z

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