Abstract
Objectives: To assess the impact of long-term pharmacotherapy with guanfacine immediate- or extended-release (GXR), administered alone or as an adjunctive to a stimulant, on weight and height in children and adolescents with attention-deficit/hyperactivity disorder (ADHD).Methods: Data were extracted from U.S. Department of Defense medical records for patients 4–17 years of age at index date (initiation of any study medication following a year without ADHD medications, or diagnosis if unmedicated) with weight/height measurements for the analysis period (January 2009–June 2013) and the previous year (baseline). Longitudinal weight and height z-scores were analyzed using multivariable regression in three cohorts: guanfacine (initial period of guanfacine exposure), first-line stimulant monotherapy (initial period of exposure), and unmedicated. Guanfacine cohort subgroups were based on previous/concurrent stimulant exposure.Results: The weight analyses included 47,910 patients (66.8% male) and the height analyses 41,248 (67.2% male). Mean initial exposure in the weight analyses was 237 days (standard deviation [SD] = 258, median = 142) for guanfacine and 257 days (SD = 284, median = 151) for first-line stimulant monotherapy, and was similar in the height analyses. Modeling indicated that guanfacine monotherapy was not associated with clinically meaningful deviations from normal z-score trajectories for weight (first-line, n = 943; nonfirst-line, n = 796) or height (first-line, n = 741; nonfirst-line, n = 644). In patients receiving guanfacine adjunctive to a stimulant, modeled weight (n = 1657) and height (n = 1343) z-scores followed declining trajectories. In this subgroup, mean standardized weight/height had decreased during previous stimulant monotherapy. For first-line stimulant monotherapy, modeled weight (n = 32,999) and height (n = 28,470) z-scores followed declining trajectories during year 1. In the unmedicated cohort, modeled weight (n = 11,515) and height (n = 10,050) z-scores were stable.Conclusions: Guanfacine monotherapy (first-line or nonfirst-line) was not associated with marked deviations from normal growth in this modeling study of children and adolescents with ADHD. In contrast, growth trajectories followed an initially declining course with stimulants, whether given alone or with adjunctive guanfacine.
Highlights
Guanfacine extended release (GXR) is a long-acting nonstimulant treatment for patients with attention-deficit/ hyperactivity disorder (ADHD) (Biederman et al 2008b; Sallee et al 2009b)
In two 2-year U.S clinical trials of GXR administered as monotherapy or adjunctive to a stimulant, mean weight, height, and body mass index (BMI) percentiles in children and adolescents with ADHD were stable at 12 months (Shire US, Inc. 2018), but increases in weight were reported as GXR-related treatment-emergent adverse events (TEAEs) in 7.1% (17/240) and 2.3% (6/259) of participants (Biederman et al 2008a; Sallee et al 2009a)
The primary analyses assessed the impact of guanfacine treatment regimens on change in standardized weight and height z-scores and were based on a data extract of electronic medical records (EMRs) that included a prescription for guanfacine
Summary
Guanfacine extended release (GXR) is a long-acting nonstimulant treatment for patients with attention-deficit/ hyperactivity disorder (ADHD) (Biederman et al 2008b; Sallee et al 2009b). Concerns about weight gain and obesity underlie the EMA recommendation to monitor weight, height, and body mass index (BMI) regularly in patients receiving GXR (European Medicines Agency 2015; Shire Pharmaceuticals Ltd. 2017). In two 2-year U.S clinical trials of GXR (doses up to 4 mg/day) administered as monotherapy or adjunctive to a stimulant, mean weight, height, and BMI percentiles in children and adolescents with ADHD were stable at 12 months (Shire US, Inc. 2018), but increases in weight were reported as GXR-related treatment-emergent adverse events (TEAEs) in 7.1% (17/240) and 2.3% (6/259) of participants (Biederman et al 2008a; Sallee et al 2009a). One participant withdrew as a result of a GXR-related TEAE of weight increase, 13.0% of participants (27/207) shifted to a higher BMI category, and 8.2% (17/207) shifted to a lower category (categories were defined as
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
More From: Journal of child and adolescent psychopharmacology
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.