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Meta-Analysis
. 2025 Apr 11;4(4):CD011885.
doi: 10.1002/14651858.CD011885.pub2.

Switching antipsychotics versus continued current treatment in people with non-responsive schizophrenia

Myrto T Samara  1   2 , Elisabeth Kottmaier  3 , Bartosz Helfer  4   5 , Claudia Leucht  6 , Nikos G Christodoulou  2 , Maximilian Huhn  7   8 , Philipp H Rothe  9 , Johannes Schneider-Thoma  1 , Stefan Leucht  1   10
Affiliations
Meta-Analysis

Switching antipsychotics versus continued current treatment in people with non-responsive schizophrenia

Myrto T Samara et al. Cochrane Database Syst Rev. .

Abstract

Background: Many people with schizophrenia do not respond to an initially prescribed antipsychotic drug. In such cases, one treatment strategy could be to switch to a different antipsychotic drug.

Objectives: To examine the effects of switching antipsychotic drugs in treating people with schizophrenia who have not responded to initial antipsychotic treatment.

Search methods: We searched the Cochrane Schizophrenia Group Trials Register (to December 2022). We inspected the references of all included studies for further relevant trials.

Selection criteria: We included all relevant randomised controlled trials (RCTs) comparing switching to a different antipsychotic drug rather than continuing treatment with the same antipsychotic drug for people with schizophrenia who did not respond to their initial antipsychotic treatment.

Data collection and analysis: At least two review authors independently extracted data. The primary outcomes were: clinically relevant response as defined by study authors; tolerability (participants leaving the study early due to adverse effects); and quality of life assessed by the change score in the 36-Item Short Form survey. We analysed dichotomous data using the risk ratio (RR) and its 95% confidence interval (CI). We analysed continuous data using mean differences (MD) and corresponding 95% CI. We assessed the risk of bias of the included studies and used GRADE to evaluate the certainty of evidence for the following outcomes: clinically relevant response, tolerability (leaving the study early due to adverse effects), quality of life score change, acceptability (leaving the study early for any reason), general mental state (average change in general mental state scores), duration of hospitalisation, and number of participants experiencing at least one adverse effect.

Main results: We included 10 RCTs with 997 participants in the review. Nine studies used a parallel design, and one used a cross-over design. Seven studies were double-blind, two were single-blind and one did not provide any detail regarding blinding. All studies included people who were non-responsive to ongoing antipsychotic treatment. The minimum duration of the ongoing antipsychotic treatment ranged from three days to two years. The length of the comparison phase varied from two weeks to six months. The studies were published between 1993 and 2022. In about half of the studies, the methods of randomisation, allocation and blinding were poorly reported. The evidence is very uncertain regarding the effect of switching antipsychotics on clinically relevant response (RR 1.25, 95% CI 0.77 to 2.03; I² = 43%; 7 studies, 693 participants), quality of life (MD -1.30, 95% CI -3.44 to 0.84; 1 study, 188 participants), Positive and Negative Syndrome Scale (PANSS) score change (MD -0.92, 95% CI -4.69 to 2.86; I² = 47%; 6 studies, 777 participants), duration of hospitalisation (in days) (MD 9.19, 95% CI -8.93 to 27.31; I² = 0%; 2 studies, 34 participants) and the number of people experiencing at least one adverse effect (RR 1.29, 95% CI 0.81 to 2.05; I² = 36%; 3 studies, 412 participants). Compared to continuing current treatment, switching antipsychotics may result in little to no difference in tolerability, defined as the number of participants leaving the study early due to adverse effects (RR 0.73, 95% CI 0.24 to 2.26; I² = 31%; 6 studies, 672 participants; low-certainty evidence) and leaving the study early for any reason (RR 0.91, 95% CI 0.71 to 1.17; I² = 0%; 6 studies, 672 participants; low-certainty evidence).

Authors' conclusions: This review synthesises currently available RCT evidence on switching antipsychotics versus continuing the same antipsychotic in individuals with schizophrenia who did not respond to their initial treatment. Overall, the evidence remains highly uncertain regarding the effects of either strategy on efficacy and safety outcomes, and no definitive recommendations can currently be made. There is an urgent need for larger, well-designed trials to identify the optimal treatment strategy for these cases.

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Conflict of interest statement

Myrto Samara ‐ in the last 36 months, MS has received honoraria as advisor and/or for lectures and/or for educational material from Lundbeck A S, Viatris and Recordati Inc.

Elisabeth Klupp ‐ nothing to declare.

Bartosz Helfer ‐ nothing to declare.

Claudia Leucht ‐ is the spouse of Stefan Leucht and thus shares his conflicts; she has nothing else to declare.

Maximilian Huhn ‐ in the last 36 months, MH has received honoraria as advisor and/or for lectures and/or for educational material from Recordati Inc. and ROVI.

Philipp Rothe ‐ nothing to declare.

Nikos Christodoulou ‐ nothing to declare.

Johannes Schneider‐Thoma ‐ nothing to declare.

Stefan Leucht ‐ in the last 36 months, SL has received honoraria as advisor and/or for lectures and/or for educational material from Angelini Pharma, Apsen, Ekademia, Eisai, Gedeon Richter, F. Hoffmann‐La Roche, Janssen Biotech, Karuna, Kynexis, Medscape, H. Lundbeck A S, Lundbeckfonden, Medichem, Merck, Mitsubishi Pharma, Novo Nordisk, Otsuka Pharmaceutical, ROVI, Recordati Inc., Sanofi‐Aventis, and Teva Pharmaceutical Industries.

Update of

  • doi: 10.1002/14651858.CD011885

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Suzuki 2013 {published data only}
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Velligan 2003 {published data only}
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Weiden 2001 {published data only}
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Weiden 2014 {published data only}
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References to ongoing studies

NCT00231101 {published data only}
    1. NCT00231101. Quetiapine decreases smoking in patients with chronic schizophrenia. http://clinicaltrials.gov/show/NCT00231101 (accessed 16 December 2015).

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