Changing Patterns of Alpha Agonist Medication Use in Children and Adolescents 2009–2011

Abstract

Objectives: The purpose of this study was to describe rates and patterns of long-and short-acting alpha agonist use for behavioral problems in a primary care population following Food and Drug Administration (FDA) approval of the long-acting alpha agonists guanfacine and clonidine. Methods: Children and adolescents 4-18 years of age, who received an alpha agonist prescription between 2009 and 2011, were identified from a sample of 45 United States primary care practices in two electronic health record-based research networks. Alpha agonist receipt was identified using National Drug Codes and medication names. The proportion of subjects receiving long-and short-acting prescriptions in each year was calculated and examined with respect to reported mental health diagnoses, and whether indications for use were on-label, had evidence from clinical trials, or had no trial evidence. Results: In a cohort of 282,875 subjects, 27,671 (10%) received any psychotropic medication and only 4,227 subjects (1.5%) received at least one prescription for an alpha agonist, most commonly a short-acting formulation (83%). Only 20% of alpha agonist use was on-label (use of long-acting formulations for attention-deficit/hyperactivity disorder [ADHD]). Most subjects (68%) received alpha agonists for indications with evidence of efficacy from clinical trials but no FDA approval, primarily short-acting formulations for ADHD and autism; 12% received alpha agonists for diagnoses lacking randomized clinical trial evidence in children, including sleep disorders and anxiety, or for which there was no documented mental health diagnosis. Rates of long-acting alpha agonist use increased more than 20-fold from 0.2% to 4%, whereas rates of short-acting alpha agonist use grew only slightly between 2009 and 2011 from 10.6% to 11.3%. Conclusions: Alpha agonist use was uncommon in this population, and most subjects received short-acting forms for conditions that were off-label, but with clinical trial evidence. The safety and efficacy of use for conditions, including sleep disorders and anxiety, lacking evidence from randomized trials, warrant further investigation.

Identification, Evaluation, and Management of Children With Autism Spectrum Disorder

“…a-adrenergic agents (eg, clonidine) and antihistamines (eg, diphenhydramine) are often prescribed to help with sleep onset or to address night-waking in children, but the literature provides little support for their use. 444,445 Disordered sleep is associated with challenging daytime behaviors in children with ASD 446 ; addressing one may help with the other.…”

A randomized, placebo-controlled trial of extended-release guanfacine in children with autism spectrum disorder and ADHD symptoms: an analysis of secondary outcome measures

“…Parents also reported mid-sleep awakening in 9 of 32 subjects taking GEXR compared to 2/32 for placebo [10]. In clinical practice, the alpha 2 receptor agonizts, clonidine and guanfacine, are commonly used off-label to help children fall asleep [42]. We included the CSHQ to assess the impact of GEXR on sleep.…”

Extended Release Guanfacine in Pediatric Anxiety Disorders: A Pilot, Randomized, Placebo-Controlled Trial

“…The results from this pilot study suggest that GXR is well tolerated in pediatric subjects with anxiety disorders, and they provide preliminary support to consider pursuing an adequately powered future efficacy study of guanfacine and potentially other antiadrenergics in youth with anxiety disorders. In addition, these data raise the possibility that GXR might be evaluated more thoroughly in patients with ADHD and cooccurring tic disorders, particularly given that a 2 agonists (1) are frequently prescribed (Fiks et al 2015); (2) reduce ADHD and tic symptoms in this population (Bloch et al 2009) and (3) that patients with tic disorders commonly present with anxiety symptoms (Coffey et al 2000). Broadly, these results suggest that the evaluation of anti-adrenergics will be of particular importance given that many youth do not respond adequately to first-line psychopharmacologic (e.g., SSRIs and SNRIs) or psychotherapeutic (e.g., CBT) interventions.…”