Frontiers in psychiatry · 2026
Treatment non-persistence in children and adolescents with Tourette syndrome newly treated with dopamine D2 receptor modulators.
СтатьяНазвание и аннотация: Перевод в очереди
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Tomczak Kinga K, Swindle Jason P, Dabbous Firas M, Gilbert Donald L, Karkanias George B, Atkinson Sarah D, Munschauer Frederick E, Mazhar Faizan, Pettersson Charlotte A, Wanaski Stephen P, Cunniff Timothy M, Isaacs David A
Аннотация
INTRODUCTION: Dopamine D2 receptor antagonists/partial agonists (D2RAs), including the US Food and Drug Administration-approved Tourette syndrome (TS) agents haloperidol, pimozide, and aripiprazole and other antipsychotics with dopamine D2 receptor-modulating properties, are prescribed for TS. This retrospective real-world study compared adverse events (AEs) and health care resource utilization (HCRU) between pediatric patients with TS newly treated versus not treated with D2RAs.
METHODS: Data were analyzed retrospectively from an electronic health records database (TriNetX Dataworks-USA Network) containing information for >119 million individuals. Two cohorts aged 6 to 17 years, from 2011-2021, were identified: a D2RA-exposed cohort indexed at first D2RA medication record with TS diagnosis during baseline (18 months before and including index) and a D2RA-nonexposed cohort indexed on a randomly selected TS diagnosis record (2011-2021) with no D2RA record during baseline or follow-up (18 months after index). Monthly D2RA use was estimated, assuming 30-day coverage into the subsequent month; incident AEs and HCRU were evaluated during follow-up using medication records, diagnosis codes, anthropometric measurements, and/or laboratory results.
RESULTS: Analyses included 1684 individuals per exact-matched cohort. In the D2RA-exposed cohort, documented D2RA medication records declined by Month 3 (38.8% of patients with a D2RA record) through Month 18 (17.9%). After adjustment for measured demographic and baseline characteristics, the D2RA-exposed cohort had higher recorded odds of incident AEs grouped as mild (e.g., sleep disorder; odds ratio [95% CI], 3.36 [2.68-4.20]), moderate (e.g., QT prolongation; 2.30 [1.65-3.20]), and severe (e.g., tardive dyskinesia; 3.01 [2.18-4.16]; all p <.0001) compared with the D2RA-nonexposed cohort. The D2RA-exposed cohort also had higher rates of all-cause and TS-related HCRU (outpatient, emergency, and inpatient encounters; adjusted incidence rate ratio range, 1.39-4.10; all p <.01).
DISCUSSION: Children and adolescents with TS newly treated with a D2RA showed substantial decline in documented D2RA medication records over follow-up and had higher recorded odds of AEs and HCRU rates than did those without D2RA exposure. These findings should be interpreted as associational rather than causal effects and may reflect residual confounding by indication, differential monitoring, and/or greater underlying disease severity/complexity in the treated cohort.
METHODS: Data were analyzed retrospectively from an electronic health records database (TriNetX Dataworks-USA Network) containing information for >119 million individuals. Two cohorts aged 6 to 17 years, from 2011-2021, were identified: a D2RA-exposed cohort indexed at first D2RA medication record with TS diagnosis during baseline (18 months before and including index) and a D2RA-nonexposed cohort indexed on a randomly selected TS diagnosis record (2011-2021) with no D2RA record during baseline or follow-up (18 months after index). Monthly D2RA use was estimated, assuming 30-day coverage into the subsequent month; incident AEs and HCRU were evaluated during follow-up using medication records, diagnosis codes, anthropometric measurements, and/or laboratory results.
RESULTS: Analyses included 1684 individuals per exact-matched cohort. In the D2RA-exposed cohort, documented D2RA medication records declined by Month 3 (38.8% of patients with a D2RA record) through Month 18 (17.9%). After adjustment for measured demographic and baseline characteristics, the D2RA-exposed cohort had higher recorded odds of incident AEs grouped as mild (e.g., sleep disorder; odds ratio [95% CI], 3.36 [2.68-4.20]), moderate (e.g., QT prolongation; 2.30 [1.65-3.20]), and severe (e.g., tardive dyskinesia; 3.01 [2.18-4.16]; all p <.0001) compared with the D2RA-nonexposed cohort. The D2RA-exposed cohort also had higher rates of all-cause and TS-related HCRU (outpatient, emergency, and inpatient encounters; adjusted incidence rate ratio range, 1.39-4.10; all p <.01).
DISCUSSION: Children and adolescents with TS newly treated with a D2RA showed substantial decline in documented D2RA medication records over follow-up and had higher recorded odds of AEs and HCRU rates than did those without D2RA exposure. These findings should be interpreted as associational rather than causal effects and may reflect residual confounding by indication, differential monitoring, and/or greater underlying disease severity/complexity in the treated cohort.