Evidence map›Paper›PMID 25841041›Full record

ReviewSchizophrenia bulletin2015

Dose Equivalents for Second-Generation Antipsychotic Drugs: The Classical Mean Dose Method.

Stefan Leucht, Myrto Samara, Stephan Heres, Maxine X Patel, Toshi Furukawa, Andrea Cipriani, John Geddes, John M Davis

Abstract readReview
PubMed Full text at PMC Publisher
In one paragraph

Review in Schizophrenia bulletin, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 161 papers, 8 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
161citing papers in PubMed, 8 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

161 citing papers in PubMed, 8 syntheses or guidelines pooled it.

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  7. Bayesian Meta-analysis of Multiple Continuous Treatments with Individual Participant-Level Data: An Application to Antipsychotic Drugs.Medical decision making : an international journal of the Society for Medical Decision Making · 2019
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  10. Antipsychotics cause reversible structural brain changes within one week.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2025
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101 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors.

Stefan LeuchtDepartment of Psychiatry and Psychotherapy, Technische Universität München Klinikum rechts der Isar, Ismaningerstr. 22, 81675 Munich, Germany; Institute of Psychiatry, Psychology and Neuroscience, King's College London, Department of Psychosis Studies, London, UK; Stefan.Leucht@lrz.tum.de.
Myrto SamaraDepartment of Psychiatry and Psychotherapy, Technische Universität München Klinikum rechts der Isar, Ismaningerstr. 22, 81675 Munich, Germany;
Stephan HeresDepartment of Psychiatry and Psychotherapy, Technische Universität München Klinikum rechts der Isar, Ismaningerstr. 22, 81675 Munich, Germany;
Maxine X PatelInstitute of Psychiatry, Psychology and Neuroscience, King's College London, Department of Psychosis Studies, London, UK;
Toshi FurukawaDepartments of Health Promotion and Human Behavior and of Clinical Epidemiology, Kyoto University Graduate School of Medicine/School of Public Health, Kyoto, Japan;
Andrea CiprianiDepartment of Psychiatry, University of Oxford, Oxford, UK;
John GeddesDepartment of Psychiatry, University of Oxford, Oxford, UK;
John M DavisPsychiatric Institute, University of Illinois at Chicago, Chicago, IL.

Funding

Department of Health NIHR/CS/009/010
6 · The paper itself

Abstract

backgroundThe concept of dose equivalence is important for many purposes. The classical approach published by Davis in 1974 subsequently dominated textbooks for several decades. It was based on the assumption that the mean doses found in flexible-dose trials reflect the average optimum dose which can be used for the calculation of dose equivalence. We are the first to apply the method to second-generation antipsychotics.

methodsWe searched for randomized, double-blind, flexible-dose trials in acutely ill patients with schizophrenia that examined 13 oral second-generation antipsychotics, haloperidol, and chlorpromazine (last search June 2014). We calculated the mean doses of each drug weighted by sample size and divided them by the weighted mean olanzapine dose to obtain olanzapine equivalents.

resultsWe included 75 studies with 16 555 participants. The doses equivalent to 1 mg/d olanzapine were: amisulpride 38.3 mg/d, aripiprazole 1.4 mg/d, asenapine 0.9 mg/d, chlorpromazine 38.9 mg/d, clozapine 30.6 mg/d, haloperidol 0.7 mg/d, quetiapine 32.3mg/d, risperidone 0.4 mg/d, sertindole 1.1 mg/d, ziprasidone 7.9 mg/d, zotepine 13.2 mg/d. For iloperidone, lurasidone, and paliperidone no data were available.

conclusionsThe classical mean dose method is not reliant on the limited availability of fixed-dose data at the lower end of the effective dose range, which is the major limitation of "minimum effective dose methods" and "dose-response curve methods." In contrast, the mean doses found by the current approach may have in part depended on the dose ranges chosen for the original trials. Ultimate conclusions on dose equivalence of antipsychotics will need to be based on a review of various methods.

Indexed as

Drug Dosage CalculationsRandomized Controlled Trials as TopicAntipsychotic AgentsHumansSchizophreniaAntipsychotic Agentsantipsychotic drugsdoseequivalenceschizophrenia

Identifiers

PMID25841041
PMCPMC4601707

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.