Real-world Adverse Event Profile and Comorbidity Index in Children and Adolescents with Tourette Syndrome (TS) Treated with Dopamine D2 Receptor Antagonists
David Isaacs1, Jason Swindle2, Firas Dabbous2, Donald Gilbert3, George Karkanias4, Sarah Atkinson4, Frederick Munschauer4, Faizan Mazhar2, Charlotte Pettersson2, Stephen Wanaski5, Timothy Cunniff5, Kinga Tomczak6
1Vanderbilt University Med Center, 2Thermo Fisher Scientific, 3Cincinnati Children's Hospital Med. Ctr., 4Emalex Biosciences, Inc., 5Paragon Biosciences, 6Boston Children's Hospital Tic Disorders and Tourette Syndrome Program
Objective:
This study explored real-world adverse events (AEs) in children and adolescents with TS treated with dopamine D2 receptor antagonists/partial agonists (D2RAs).
Background:
Psychiatric comorbidities are prevalent in TS populations. D2RAs reduce tic severity but pose a substantial risk of AEs.
Design/Methods:
This was a retrospective health records database (TriNetX Dataworks-USA Network) analysis. A D2RA-exposed cohort was indexed at first D2RA medication record (2011-2021) with prior TS diagnosis (ICD-9-CM:307.23/ICD-10-CM:F952). A nonexposed cohort was indexed at a randomly selected record with TS diagnosis (2011-2021). Individuals (6-17 years) had ≥1 provider encounter during baseline/follow-up (18 months before/after index). Cohorts were exact-matched (age group/index year/region/sex). Baseline comorbidity index was calculated using a validated pediatric comorbidity index (higher scores represented increased hospitalization risk). Incident AEs (per diagnosis codes/anthropometric data/laboratory results) were identified during follow-up and cohorts compared using standardized mean difference (SMD; ≥|0.10| indicated meaningful imbalance).
Results:
1684 matched individuals were included in each cohort. Mean (SD) baseline comorbidity index was higher for D2RA-exposed versus nonexposed cohort (3.4 [3.5] vs 2.1 [2.5]; SMD=0.44). During follow-up, the D2RA-exposed cohort was more likely to experience sleep disorders (7.7% vs 2.4%; SMD=0.24), obsessive-compulsive disorder (6.2% vs 2.6%; SMD=0.18), mild (15.0% vs 3.9%; SMD=0.39) and moderate (6.9% vs 1.1%; SMD=0.30) metabolic AEs, depression (6.3% vs 2.7%; SMD=0.18), and suicidal ideation/behavior/attempt (5.8% vs 2.1%; SMD=0.19). Dystonia, akathisia, and tardive dyskinesia were reported in 0.5% (n=8), 0.2% (n=3), and 0.1% (n=1) of patients, respectively, in the D2RA-exposed cohort; none were reported in the nonexposed cohort.
Conclusions:
In this real-world study of children and adolescents with TS, metabolic and neuropsychiatric AEs were more common among those treated with D2RAs. Alternative treatment strategies and pharmacologic interventions are needed that can provide sustained relief of symptoms with minimal risk of AEs.
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