Evidence map›Paper›PMID 31860457›Full record

SynthesisThe lancet. Psychiatry2020

Comparative effects of 18 antipsychotics on metabolic function in patients with schizophrenia, predictors of metabolic dysregulation, and association with psychopathology: a systematic review and network meta-analysis.

Toby Pillinger, Robert A McCutcheon, Luke Vano, Yuya Mizuno, Atheeshaan Arumuham, Guy Hindley, Katherine Beck, Sridhar Natesan, Orestis Efthimiou, Andrea Cipriani and 1 more

2 registry-linked trialsOpen access · hybridAbstract readComparative StudyNetwork Meta-AnalysisSystematic Review
PubMed Full text at PMC Publisher
In one paragraph

Synthesis in The lancet. Psychiatry, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 555 papers, 18 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
555citing papers in PubMed, 18 pooled it
56.2field-weighted citation impact, top 1% of its field
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.

NCT07045142 phase3recruitingnot on this mapstarted 2025, after this paper: background citation

Metformin Alleviates Abnormal Glucose Metabolism Induced by Statins in Schizophrenia Patients: A Randomized, Double-Blind, Placebo-Controlled Multicenter Clinical Study

TypeinterventionalSponsorCentral South UniversityRan2025 to 2028Enrolled400ConditionsSchizophreniaArmsAtorvastatin, Metformin, Placebo
NCT07371325 nacompletednot on this mapstarted 2024, after this paper: background citation

Efficacy of Pediococcus Acidilactici as add-on to Antipsychotic Drugs on Metabolic Syndrome Disturbances in First-episode Psychosis and Schizophrenia Spectrum Disorders. A Double-blind Placebo-controlled Trial.

TypeinterventionalSponsorManuel Jesús Cuesta ZuritaRan2024 to 2026Enrolled36ConditionsSCHIZOPHRENIA 1 (Disorder), Metabolic Abnormalities, Postbiotic SupplementArmsPediococcus acidilactici, pA1c®HI postbiotic supplementation taking participants, Atypical antipsychotics (AAP)
3 · Its place in the literature

Who cites it

555 citing papers in PubMed, 18 syntheses or guidelines pooled it, 955 citations in OpenAlex.

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  10. The Australian and New Zealand journal of psychiatry · 2026
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495 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

11 authors at 6 institutions in 3 countries.

Toby PillingerInstitute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK; MRC London Institute of Medical Sciences, Faculty of Medicine, Imperial College London, Hammersmith Hospital Campus, London, UK. Electronic address: toby.pillinger@kcl.ac.uk.
Robert A McCutcheonInstitute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK; MRC London Institute of Medical Sciences, Faculty of Medicine, Imperial College London, Hammersmith Hospital Campus, London, UK.
Luke VanoInstitute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK; MRC London Institute of Medical Sciences, Faculty of Medicine, Imperial College London, Hammersmith Hospital Campus, London, UK.
Yuya MizunoInstitute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK; MRC London Institute of Medical Sciences, Faculty of Medicine, Imperial College London, Hammersmith Hospital Campus, London, UK; Department of Neuropsychiatry, Keio University School of Medicine, Tokyo, Japan.
Atheeshaan ArumuhamInstitute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK; MRC London Institute of Medical Sciences, Faculty of Medicine, Imperial College London, Hammersmith Hospital Campus, London, UK.
Guy HindleyInstitute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK; MRC London Institute of Medical Sciences, Faculty of Medicine, Imperial College London, Hammersmith Hospital Campus, London, UK.
Katherine BeckInstitute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK; MRC London Institute of Medical Sciences, Faculty of Medicine, Imperial College London, Hammersmith Hospital Campus, London, UK.
Sridhar NatesanInstitute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK; MRC London Institute of Medical Sciences, Faculty of Medicine, Imperial College London, Hammersmith Hospital Campus, London, UK.
Orestis EfthimiouInstitute of Social and Preventive Medicine, University of Bern, Bern, Switzerland.
Andrea CiprianiDepartment of Psychiatry, University of Oxford, Oxford, UK; Oxford health NHS Foundation Trust, Warneford Hospital, Oxford, UK.
Oliver D HowesInstitute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK; MRC London Institute of Medical Sciences, Faculty of Medicine, Imperial College London, Hammersmith Hospital Campus, London, UK.
King's College London · GBImperial College London · GBMRC London Institute of Medical Sciences · GBHammersmith Hospital · GBOxford Health NHS Foundation Trust · GBUniversity of Bern · CH

Funding

Medical Research Council G0700995Medical Research Council MC_PC_17215Medical Research Council MC_U120097115Medical Research Council MR/L022176/1Medical Research Council MR/N026063/1Medical Research Council MR/N027078/1Wellcome TrustWellcome Trust 09489/Z/10/ZWellcome Trust 200102/Z/15/Z
6 · The paper itself

Abstract

backgroundAntipsychotic treatment is associated with metabolic disturbance. However, the degree to which metabolic alterations occur in treatment with different antipsychotics is unclear. Predictors of metabolic dysregulation are poorly understood and the association between metabolic change and change in psychopathology is uncertain. We aimed to compare and rank antipsychotics on the basis of their metabolic side-effects, identify physiological and demographic predictors of antipsychotic-induced metabolic dysregulation, and investigate the relationship between change in psychotic symptoms and change in metabolic parameters with antipsychotic treatment.

methodsWe searched MEDLINE, EMBASE, and PsycINFO from inception until June 30, 2019. We included blinded, randomised controlled trials comparing 18 antipsychotics and placebo in acute treatment of schizophrenia. We did frequentist random-effects network meta-analyses to investigate treatment-induced changes in body weight, BMI, total cholesterol, LDL cholesterol, HDL cholesterol, triglyceride, and glucose concentrations. We did meta-regressions to examine relationships between metabolic change and age, sex, ethnicity, baseline weight, and baseline metabolic parameter level. We examined the association between metabolic change and psychopathology change by estimating the correlation between symptom severity change and metabolic parameter change.

findingsOf 6532 citations, we included 100 randomised controlled trials, including 25 952 patients. Median treatment duration was 6 weeks (IQR 6-8). Mean differences for weight gain compared with placebo ranged from -0·23 kg (95% CI -0·83 to 0·36) for haloperidol to 3·01 kg (1·78 to 4·24) for clozapine; for BMI from -0·25 kg/m

interpretationMarked differences exist between antipsychotics in terms of metabolic side-effects, with olanzapine and clozapine exhibiting the worst profiles and aripiprazole, brexpiprazole, cariprazine, lurasidone, and ziprasidone the most benign profiles. Increased baseline weight, male sex, and non-white ethnicity are predictors of susceptibility to antipsychotic-induced metabolic change, and improvements in psychopathology are associated with metabolic disturbance. Treatment guidelines should be updated to reflect our findings. However, the choice of antipsychotic should be made on an individual basis, considering the clinical circumstances and preferences of patients, carers, and clinicians.

fundingUK Medical Research Council, Wellcome Trust, National Institute for Health Research Oxford Health Biomedical Research Centre.

Indexed as

Antipsychotic AgentsLipid MetabolismSchizophreniaBlood GlucoseBody Mass IndexHumansRandomized Controlled Trials as TopicWeight GainAntipsychotic AgentsBlood Glucose

Identifiers

PMID31860457
PMCPMC7029416
OpenAlexW2982167270

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

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.