Weight and Height in Children and Adolescents with Attention-Deficit/Hyperactivity Disorder: A Longitudinal Database Study Assessing the Impact of Guanfacine, Stimulants, and No Pharmacotherapy

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.

Keywords: attention-deficit/hyperactivity disorder; guanfacine; height; stimulant; weight.

FIG. 1.

Study cohorts. ^aFirst study medication is guanfacine monotherapy; subsequent stimulant prescriptions permissible. ^bStimulant exposure ended before or up to 28 days after first guanfacine prescription. Index date (stimulant initiation) could predate the start of the baseline period. Stimulant exposure before guanfacine initiation need not be continuous. ^cFirst guanfacine prescription simultaneous with a stimulant prescription or concurrent with stimulant exposure for more than 28 days. Initial period of exposure ends at discontinuation of guanfacine and/or stimulant. Index date (stimulant initiation) could predate the start of the baseline period and stimulant exposure before guanfacine initiation need not be continuous. ^dFirst study medication is stimulant monotherapy; no guanfacine prescription at any time. ^eNo prescriptions for any ADHD medication (a study medication or atomoxetine). ^fBaseline measurement is the most recent weight or height measurement during the baseline period (the 12 months before time = 0). ^gGuanfacine initiation date in the guanfacine cohort, index date in other cohorts. ADHD, attention-deficit/hyperactivity disorder.

FIG. 2.

Calculation of prescribed amount (in days) of a study medication for different drugs or for different doses of the same drug: with no overlaps between prescriptions (a), with overlaps ≤90 days (b), or with overlaps >90 days (c). ^aStudy medications: guanfacine (any formulation of GXR or GIR); stimulant (any formulations of amphetamine or methylphenidate). ^bFor example, GXR 4 mg/day. ^cFor example, GXR <> 4 mg/day or GIR any dose. GIR, guanfacine immediate release; GXR, guanfacine extended release.

FIG. 3.

Modeled z-scores for weight (a–c) and height (d–f) in the guanfacine cohort for all patients (a, d), males (b, e), and females (c, f). Solid lines show the trajectories when all other predictor variables are held constant to their overall means for patients in the guanfacine cohort, apart from “stimulant supply preguanfacine,” which is held constant to the mean of each subgroup. Traces show a random sample of patients. Numbers below the x axes indicate the numbers of patients with weight/height measurements on or after each time point.

FIG. 4.

Modeled z-scores for weight (a–c) and height (d–f) in the first-line stimulant monotherapy and unmedicated cohorts for all patients (a, d), males (b, e), and females (c, f). Solid lines show the trajectories when all other predictor variables are held constant to the mean of each cohort. Traces show a random sample of patients. Numbers below the x axes indicate the numbers of patients with weight/height measurements on or after each time point.