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Antipsychotic drugs v. barbiturates or benzodiazepines used as active placebos for schizophrenia: a systematic review and meta-analysis

Published online by Cambridge University Press:  18 October 2019

Spyridon Siafis Open the ORCID record for Spyridon Siafis [Opens in a new window] ,
Giacomo Deste ,
Anna Ceraso ,
Christian Mussoni ,
Antonio Vita ,
Senad Hasanagic ,
Johannes Schneider-Thoma Open the ORCID record for Johannes Schneider-Thoma [Opens in a new window] ,
Georgios Papazisis Open the ORCID record for Georgios Papazisis [Opens in a new window] ,
John M Davis  and
Stefan Leucht Open the ORCID record for Stefan Leucht [Opens in a new window]
Spyridon Siafis*
Affiliation:
Department of Psychiatry and Psychotherapy, School of Medicine, Technische Universität München, München, Germany
Giacomo Deste
Affiliation:
Department of Psychiatry, Spedali Civili Hospital, Brescia, Italy
Anna Ceraso
Affiliation:
Department of Psychiatry, Spedali Civili Hospital, Brescia, Italy
Christian Mussoni
Affiliation:
Department of Psychiatry, Spedali Civili Hospital, Brescia, Italy
Antonio Vita
Affiliation:
Department of Psychiatry, Spedali Civili Hospital, Brescia, Italy
Senad Hasanagic
Affiliation:
Medical Center of the University of Sarajevo, Sarajevo, Bosnia and Herzegovina
Johannes Schneider-Thoma
Affiliation:
Department of Psychiatry and Psychotherapy, School of Medicine, Technische Universität München, München, Germany
Georgios Papazisis
Affiliation:
Department of Clinical Pharmacology, School of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece
John M Davis
Affiliation:
Department of Psychiatry, University of Illinois at Chicago, Chicago, USA Illinois and Maryland Psychiatric Research Center, Baltimore, Maryland, USA
Stefan Leucht
Affiliation:
Department of Psychiatry and Psychotherapy, School of Medicine, Technische Universität München, München, Germany
*
Author for correspondence: Spyridon Siafis, E-mail: [email protected]
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Abstract

Background

Comparisons of antipsychotics with placebo can be biased by unblinding due to side effects. Therefore, this meta-analysis compared the efficacy of antipsychotics for acute schizophrenia in trials using barbiturates or benzodiazepines as active placebos.

Methods

Randomized controlled trials (RCTs) in acute schizophrenia with at least 3 weeks duration and comparing any antipsychotic with barbiturates or benzodiazepines were eligible. ClinicalTrials.gov, CENTRAL, EMBASE, MEDLINE, PsycINFO, PubMed, WHO-ICTRP as well as previous reviews were searched up to 9 January 2018. Two separate meta-analyses, one for barbiturates and one for benzodiazepines, were conducted using random-effects models. The primary outcome was response to treatment, and mean values of schizophrenia rating scales and dropouts were analyzed as secondary outcomes. This study is registered with PROSPERO (CRD42018086263).

Results

Seven barbiturate-RCTs (number of participants n = 1736), and two benzodiazepine-RCTs (n = 76) were included in the analysis. The studies were published between 1960 and 1968 and involved mainly chronically ill patients. More patients on antipsychotics in comparison to barbiturates achieved a ‘good’ response (36.2% v. 16.8%; RR 2.15; 95% CI 1.36–3.41; I2 = 48.9) and ‘any’ response (57.4% v. 27.8%; RR 2.07; 95% CI 1.35–3.18; I2 = 68.2). In a single small trial (n = 60), there was no difference between antipsychotics and benzodiazepines on ‘any’ response (74.7% v. 65%; RR 1.15; 95% CI 0.82–1.62).

Conclusions

Antipsychotic drugs were more efficacious than barbiturates, based on a large sample size. Response ratios were similar to those observed in placebo-controlled trials. The results on benzodiazepines were inconclusive due to the small number of studies and participants.

Keywords

First-generationphenobarbitalphenothiazinesrandomizedresponse
Type
Original Articles
Information
Psychological Medicine , Volume 50 , Issue 15 , November 2020 , pp. 2622 - 2633
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Copyright
Copyright © Cambridge University Press 2019

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