ArticleWorld psychiatry : official journal of the World Psychiatric Association (WPA)2018
Tardive dyskinesia risk with first- and second-generation antipsychotics in comparative randomized controlled trials: a meta-analysis.
Article in World psychiatry : official journal of the World Psychiatric Association (WPA), 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 76 papers, 12 of them syntheses that pooled it.
What it found
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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.
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.
Who cites it
76 citing papers in PubMed, 12 syntheses or guidelines pooled it, 194 citations in OpenAlex.
- Integrating genome-wide and epigenome-wide associations for antipsychotic induced extrapyramidal side effects.Psychopharmacology · 2026Pooled it
- Initial physical health assessment for psychosis in Australia and New Zealand: 2026 recommendations.The Australian and New Zealand journal of psychiatry · 2026Guideline
- Strategies for Switching between Oral Postsynaptic Antidopaminergic Antipsychotics in Patients with Schizophrenia: A Systematic Review.CNS drugs · 2025Pooled it
- Efficacy and acceptability of pharmacological interventions for tardive dyskinesia in people with schizophrenia or mood disorders: a systematic review and network meta-analysis.Molecular psychiatry · 2025Pooled it
- Tardive Dyskinesia with Antipsychotic Medication in Children and Adolescents: A Systematic Literature Review.Drug safety · 2024Pooled it
- Antidepressant and antipsychotic side-effects and personalised prescribing: a systematic review and digital tool development.The lancet. Psychiatry · 2023Pooled it
- Pharmacological interventions for antipsychotic-related sialorrhea: a systematic review and network meta-analysis of randomized trials.Molecular psychiatry · 2023Pooled it
- Antipsychotics for schizophrenia spectrum disorders with catatonic symptoms.The Cochrane database of systematic reviews · 2022Pooled it
- Examination of Dosing of Antipsychotic Drugs for Relapse Prevention in Patients With Stable Schizophrenia: A Meta-analysis.JAMA psychiatry · 2021Pooled it
- Adjunctive metformin for antipsychotic-induced dyslipidemia: a meta-analysis of randomized, double-blind, placebo-controlled trials.Translational psychiatry · 2020Pooled it
- Treatment Recommendations for Tardive Dyskinesia.Canadian journal of psychiatry. Revue canadienne de psychiatrie · 2019Pooled it
- Treatment of tardive dyskinesia with VMAT-2 inhibitors: a systematic review and meta-analysis of randomized controlled trials.Drug design, development and therapy · 2018Pooled it
- Trial
- Tardive Dyskinesia in Patients Receiving Continuous Versus Intermittent Oral Metoclopramide: A Retrospective Real World Study.Neurogastroenterology and motility · 2026Article
- A Case Report: Successful Management of Mixed Tardive Syndrome With Combination Pharmacotherapy in a 19-Year-Old Female With Schizophrenia.Clinical case reports · 2026Article
- Clinical and neurobiological correlates of tardive dyskinesia in schizophrenia spectrum disorders and mood disorders.Schizophrenia (Heidelberg, Germany) · 2026Article
- Real-world comprehensive care of people living with schizophrenia: recommendations across different settings and clinical stages.World psychiatry : official journal of the World Psychiatric Association (WPA) · 2026Article
- Predicting functional remission after antipsychotic discontinuation: a real-world study in schizophrenia.Psychological medicine · 2026Article
- Development of a patient decision aid prototype on the decision to continue, reduce or discontinue antipsychotic medication following remission of first-episode psychosis.BJPsych open · 2026Article
- Budget impact of xanomeline and trospium chloride for the treatment of adults with schizophrenia in the United States.Journal of managed care & specialty pharmacy · 2026Article
16 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Tardive dyskinesia (TD) risk with D2/serotonin receptor antagonists or D2 receptor partial agonists (second-generation antipsychotics, SGAs) is considered significantly lower than with D2 antagonists (first-generation antipsychotics, FGAs). As some reports questioned this notion, we meta-analyzed randomized controlled studies (RCTs) to estimate the risk ratio (RR) and annualized rate ratio (RaR) of TD comparing SGAs vs. FGAs and SGAs vs. SGAs. Additionally, we calculated raw and annualized pooled TD rates for each antipsychotic. Data from 57 head-to-head RCTs, including 32 FGA and 86 SGA arms, were meta-analyzed, yielding 32 FGA-SGA pairs and 35 SGA-SGA pairs. The annualized TD incidence across FGA arms was 6.5% (95% CI: 5.3-7.8%) vs. 2.6% (95% CI: 2.0-3.1%) across SGA arms. TD risk and annualized rates were lower with SGAs vs. FGAs (RR=0.47, 95% CI: 0.39-0.57, p<0.0001, k=28; RaR=0.35, 95% CI: 0.28-0.45, p<0.0001, number-needed-to-treat, NNT=20). Meta-regression showed no FGA dose effect on FGA-SGA comparisons (Z=-1.03, p=0.30). FGA-SGA TD RaRs differed by SGA comparator (Q=21.8, df=7, p=0.003), with a significant advantage of olanzapine and aripiprazole over other non-clozapine SGAs in exploratory pairwise comparisons. SGA-SGA comparisons confirmed the olanzapine advantage vs. non-clozapine SGAs (RaR=0.66, 95% CI: 0.49-0.88, p=0.006, k=17, NNT=100). This meta-analysis confirms a clinically meaningfully lower TD risk with SGAs vs. FGAs, which is not driven by high dose FGA comparators, and documents significant differences with respect to this risk between individual SGAs.
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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.