Extended-Release Guanfacine Hydrochloride is Safe and Effective as Mono- and Adjunctive Therapy in Children and Adolescents with ADHD: A Naturalistic, Multi-Center, Patient-Reported Outcome Measures–Based Study

Aims: Attention-deficit hyperactivity disorder (ADHD) is characterized by impairing and age-inappropriate inattention, hyperactivity, and impulsivity. Extended-release guanfacine hydrochloride (GXR) is a selective α2A-adrenergic agonist approved as mono- and adjunctive therapy to psychostimulant medications for ADHD. This multicenter retrospective study aimed to assess patients with ADHD initiating treatment with GXR as mono- and adjunctive therapy in a non-Western, real-world clinical setting. Methods: The study was designed as a naturalistic, Patient-Reported Outcome Measures (PROMs)-based, clinic-based, multi-center study; thirty-two child and adolescent psychiatry clinics from 26 cities located in seven geographical regions of Türkiye were included. Clinicians evaluated ADHD symptom severity at baseline and at the end of the 6th month with Clinical Global Impressions (CGI)-Severity, Improvement, and Adverse Effect scales while parents evaluated symptoms with the DSM-IV-Based Screening Scale for Disruptive Behavior Disorders. Adverse effects after GXR treatment were determined from patient records. Dose equivalents for stimulants, antidepressants, antipsychotics, and mood stabilizers used concurrently with GXR were calculated. Univariate and bivariate analyses along with linear mixed models were used to model change. Logistic regression was used to evaluate predictors of treatment response in sensitivity analysis. Results: Five hundred and sixty-seven patients ( n = 437, 77.1% male) with a mean age of 11.2 ( SD = 2.8) years were enrolled. Comorbid diagnoses were common (82.4%) along with combination therapy (85.0%). GXR at a median dose of 2.0 to 3.0 mg/day was associated with improvement and the rate of adverse effects was low. GXR showed differential symptom-domain effects, with greater improvement in hyperactive-impulsive (HI) compared to inattentive (IA) symptoms. Children with comorbid autism spectrum disorder (ASD; n = 175, 30.0% of the sample) showed notable clinical improvement. Response was modified by baseline symptom severity. Conclusion: GXR may be a viable treatment option for children and adolescents with ADHD and various comorbidities among Turkish youth in real-world clinical populations, with baseline symptom severity as a potential modifier of response. The differential response favoring HI symptoms and notable effectiveness in comorbid ASD represent clinically important findings of this naturalistic, PROM-based study.