“Prevalence, incidence, modifiable and non-modifiable factors associated with tardive dyskinesia in children and adolescents exposed to antipsychotics: a systematic review and meta-analysis”

Abstract Background. Antipsychotics are increasingly prescribed to children and adolescents, yet the cumulative risk of tardive dyskinesia (TD) in this developmentally vulnerable population is poorly quantified. We aimed to estimate the prevalence and annualized incidence of TD in youth exposed to antipsychotics and identify clinically relevant moderators. Methods. We conducted a PRISMA 2020-compliant systematic review and random-effects meta-analysis (PubMed/PsycINFO/Embase, 13 July 2026, no language restrictions). We included cross-sectional studies, prospective and retrospective cohorts, and randomized or non-randomized trials enrolling >=10 children or adolescents (<=18 years) with an ICD or DSM mental disorder and exposed to any first-generation (FGA) or second-generation antipsychotic (SGA), with longitudinal studies requiring >=6 months follow-up. Primary outcomes were point or lifetime prevalence and annualized incidence rate (per 1,000 person-years) of TD. Pre-specified subgroup analyses examined antipsychotic generation, study design, mental disorder category, study quality, and sample size; meta-regression examined age, sex, race, chlorpromazine-equivalent dose, follow-up duration, year of data collection, and sample size. Methodological quality was rated with NIH tools. Random-effects models used a generalized linear mixed model with logit transformation. Results. We pooled 44 prevalence studies (n=18,173; 194 events) and 27 incidence studies (62 events; 40,893 person-years). Pooled prevalence of TD was 0.67% (95% CI 0.30-1.51; I2=88.8%) and pooled annualized incidence was 1.91 per 1,000 person-years (95% CI 0.59-6.22; I2=88.3%). Prevalence differed significantly by antipsychotic generation: 0.32% (0.13-0.81; k=31) with SGA, 7.53% (3.15-16.95; k=5) with FGA, 2.18% (0.47-9.61; k=8) with mixed FGA/SGA (subgroup p<0.0001); by study design (RCT 0.30% [0.11-0.80; k=25] to cross-sectional studies 6.77% [1.23-29.63; k=3]; p=0.0024); and by disorder, ranging from 0.29% (0.12-0.68; k=7) in disruptive disorders to 20.39% (13.69-29.26) in the intellectual-disability study (p<0.0001). Incidence differed significantly by study design (prospective cohorts 22.15 [4.50-108.99; k=4] vs RCT 1.08 [0.16-7.43; k=18]; p=0.035) and by disorder (from 0.27 [0.02-4.50; k=6] in schizophrenia-spectrum through 4.01 [1.10-14.62; k=10] in neurodevelopmental, 14.14 [2.10-95.27; k=2] in bipolar, to 65.91 [47.33-91.80; k=2] in mixed mental/behavioral/neurodevelopmental disorders; p<0.0001). Meta-regression: prevalence increased with the proportion of FGA exposure (β=0.034, 95% CI 0.017 to 0.050; k=38; p<0.0001) and the proportion of Black participants (β=0.076, 95% CI 0.017 to 0.134; k=17; p=0.011), and decreased with later year of data collection (β=−0.123, 95% CI −0.194 to −0.053; k=44; p=0.00062). Incidence decreased with longer mean follow-up, potentially reflecting low estimates in retrospective studies (β=−0.019, 95% CI −0.033 to −0.005; k=27; p=0.0058). Interpretation. The risk of TD in antipsychotic-treated children and adolescents is higher with FGA exposure, in neurodevelopmental disorders, and in samples with a higher proportion of Black participants, and is likely under-measured and under-diagnosed in real-world clinical practice.