Research Article: Serum ferritin critical threshold fluctuations predict antipsychotic treatment discontinuation in pediatric Tic disorders: a retrospective cohort study
Abstract:
To determine whether dynamic fluctuations in serum ferritin below a critical threshold (30?ng/mL) independently predict antipsychotic treatment discontinuation in children with tic disorders, and to evaluate effect modification by antipsychotic class.
A single-center retrospective cohort study analyzed electronic medical records (2022–2024) of 228 children (aged 6–16 years) with Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5)-diagnosed tic disorders receiving first-line antipsychotics. Participants were stratified by ferritin fluctuation patterns: high-fluctuation (coefficient of variation [CV] ?25% with ?1 value <30?ng/mL; n =?78) vs. low-fluctuation (CV <25% or all values ?30?ng/mL; n =?150). The primary outcome was treatment discontinuation. Cox regression models were sequentially adjusted for demographic/clinical factors and an extended set of covariates (including nutritional and socioeconomic proxies).
Over a 22.4-month median follow-up, high-fluctuation patients showed significantly higher discontinuation rates (60.3% vs. 24.0%; P <?0.001), with lack of efficacy being a more frequent reason in this group. After full adjustment, high ferritin fluctuation predicted a >2-fold discontinuation risk (hazard ratio [HR]?=?2.24, 95% confidence interval [CI]: 1.43–3.52; P <?0.001), which remained significant after further adjustment for extended covariates (HR?=?2.11, 95% CI: 1.34–3.33, P =?0.001). An exploratory analysis indicated that high fluctuation was also associated with a slower rate of tic symptom improvement over time ( P =?0.002). Subgroup analysis revealed a stronger association with typical antipsychotics (HR?=?4.12) vs. atypical agents (HR?=?1.87; P interaction?=?0.021). Results were robust across sensitivity analyses, including assessment of potential monitoring bias. Baseline ferritin <30?ng/mL alone was non-predictive (HR?=?1.18; P =?0.42).
Dynamic ferritin fluctuations below 30?ng/mL independently predict antipsychotic discontinuation and poorer symptomatic improvement in pediatric tic disorders, with heightened risk for typical antipsychotic users. Serial ferritin monitoring may identify high-risk patients for early intervention.
Introduction:
Tic disorders are among the most common neurodevelopmental conditions in childhood, typically manifesting as sudden, recurrent, non-rhythmic motor or vocal tics. Epidemiological surveys estimate that up to 25% of children experience tics at some point during development, particularly between the ages of 5 and 12 years, though most cases are transient in nature ( 1 ). Chronic tic disorders, including Tourette syndrome (TS), are more persistent and affect approximately 0.6% of children worldwide ( 2 ). In the United…
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