Schneider Gary, Banaschewski Tobias, Feldman Brian L, Gustafsson Per A, Murphy Brian, Reynolds Matthew, Coghill David R, Spalding William M
1 Evidera, Waltham, Massachusetts.
2 Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
J Child Adolesc Psychopharmacol. 2019 May;29(4):285-304. doi: 10.1089/cap.2018.0132. Epub 2019 Apr 3.
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). 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 -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. 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 -score trajectories for weight (first-line, = 943; nonfirst-line, = 796) or height (first-line, = 741; nonfirst-line, = 644). In patients receiving guanfacine adjunctive to a stimulant, modeled weight ( = 1657) and height ( = 1343) -scores followed declining trajectories. In this subgroup, mean standardized weight/height had decreased during previous stimulant monotherapy. For first-line stimulant monotherapy, modeled weight ( = 32,999) and height ( = 28,470) -scores followed declining trajectories during year 1. In the unmedicated cohort, modeled weight ( = 11,515) and height ( = 10,050) -scores were stable. 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.
评估单独使用或作为兴奋剂辅助药物使用的胍法辛速释或缓释制剂(GXR)长期药物治疗对注意力缺陷多动障碍(ADHD)儿童和青少年体重及身高的影响。数据取自美国国防部医疗记录,涉及索引日期(在无ADHD药物治疗一年后开始使用任何研究药物,或未用药时的诊断日期)年龄在4至17岁的患者,分析期(2009年1月至2013年6月)及前一年(基线期)有体重/身高测量值。在三个队列中使用多变量回归分析纵向体重和身高分数:胍法辛组(胍法辛暴露初期)、一线兴奋剂单药治疗组(暴露初期)和未用药组。胍法辛组亚组基于既往/同时使用兴奋剂的情况。体重分析纳入47,910例患者(66.8%为男性),身高分析纳入41,248例(67.2%为男性)。体重分析中胍法辛的平均初始暴露时间为237天(标准差[SD]=258,中位数=142),一线兴奋剂单药治疗为257天(SD=284,中位数=151),身高分析情况类似。模型显示,胍法辛单药治疗与体重(一线治疗,=943;非一线治疗,=796)或身高(一线治疗,=741;非一线治疗,=644)的正常分数轨迹无临床意义的偏差。在接受胍法辛作为兴奋剂辅助药物的患者中,模型化的体重(=1657)和身高(=1343)分数呈下降轨迹。在该亚组中,既往兴奋剂单药治疗期间平均标准化体重/身高有所下降。对于一线兴奋剂单药治疗,模型化的体重(=32,999)和身高(=28,470)分数在第1年呈下降轨迹。在未用药队列中,模型化的体重(=1,1515)和身高(=10,050)分数稳定。在这项针对ADHD儿童和青少年的模型研究中,胍法辛单药治疗(一线或非一线)与正常生长无明显偏差。相比之下,无论单独使用还是与胍法辛联合使用,兴奋剂治疗后的生长轨迹最初均呈下降趋势。