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Irritability and Emotion Dysregulation Predict Escitalopram Response in Adolescents with Generalized Anxiety Disorder: A Secondary Analysis of a Randomized, Double-Blind, Placebo-Controlled Trial

AI Summary
  • Higher baseline child- and parent-reported irritability predicted lower escitalopram treatment response in adolescents with GAD, independent of baseline anxiety severity.
  • Longitudinal reductions in child- and parent-reported irritability were associated with concurrent reductions in anxiety symptom severity over time.
  • Irritability represents a clinically important illness characteristic and a potential treatment target in paediatric anxiety disorders.
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J Child Adolesc Psychopharmacol. 2026 Sep 23:10445463261490409. doi: 10.1177/10445463261490409. Online ahead of print.

ABSTRACT

OBJECTIVE: Irritability is increasingly recognized as an important aspect of emotion dysregulation in pediatric anxiety disorders. However, the relationship between irritability and treatment outcome in adolescents with generalized anxiety disorder (GAD) remains poorly understood. We examined whether irritability predicts clinical outcome and whether changes in irritability are associated with treatment-related improvement.

METHODS: This secondary analysis utilized data from a randomized, double-blind, placebo-controlled trial of escitalopram in adolescents (12-17 years) with GAD (N = 51). Irritability was assessed longitudinally using child- and parent-reported Affective Reactivity Index (ARI) scores. Clinical outcomes included treatment response (Clinical Global Impressions-Improvement ≤ 2) and anxiety symptom severity measured by the Pediatric Anxiety Rating Scale. Logistic regression and longitudinal mixed-effects models examined associations between irritability and treatment outcome.

RESULTS: Higher baseline child-reported irritability was associated with a lower likelihood of treatment response (adjusted OR per 1-SD increase = 0.51, 95% credible intervals [95% CrI] 0.35-0.73), as was higher parent-reported irritability (adjusted OR per 1-SD increase = 0.58, 95% CrI 0.40-0.83). Additionally, longitudinal reductions in child-reported (adjusted β = 0.27, p < 0.001) and parent-reported irritability (adjusted β = 0.18, p = 0.002) were associated with reductions in anxiety symptoms over time. Baseline irritability was not associated with statistically significant subsequent changes in anxiety symptom severity.

CONCLUSIONS: Irritability is associated with clinical response in adolescents with GAD. Child- and parent-reported irritability predicted treatment response independent of baseline anxiety severity, while reductions in irritability paralleled improvement in anxiety. These findings suggest that irritability may represent a clinically important aspect of illness and a potential treatment target in pediatric anxiety disorders.

PMID:42773855 | DOI:10.1177/10445463261490409

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