Pozzi Marco, Pisano Simone, Marano Giuseppe, Carnovale Carla, Bravaccio Carmela, Rafaniello Concetta, Capuano Annalisa, Rossi Francesco, Rizzo Renata, Bernardini Renato, Nobile Maria, Molteni Massimo, Clementi Emilio, Biganzoli Elia, Radice Sonia
1 Scientific Institute IRCCS Eugenio Medea , Lecco, Italy .
2 Department of Neurosciences, AORN Santobono-Pausilipon , Naples, Italy .
J Child Adolesc Psychopharmacol. 2019 Mar;29(2):133-140. doi: 10.1089/cap.2018.0092. Epub 2018 Nov 16.
Second-generation antipsychotics (SGAs) increase appetite and weight, leading toward a metabolic syndrome. Risperidone and aripiprazole, the most widely used pediatric SGAs, have been studied predominantly in short-term clinical trials, where risperidone leads to a rapid weight increase and aripiprazole to a slower one, while long-term effects are not yet elucidated. Factors that may influence weight gain are likewise not clarified, although baseline weight, previous SGA exposure, pubertal status, and type of SGA have been suggested as moderators. We analyzed weight gain induced by risperidone and aripiprazole in a sample of pediatric outpatients enrolled into a 2-year observational study.
We assessed at several time points their body mass index (BMI)-Z scores (age and sex-corrected and referred to national norms). We used hierarchical mixed-effects modeling to design BMI-Z trajectories and observed the effects of several variables on determining them.
The study group comprised of 127 patients, predominantly males (79%), of 12.6 years on average, treated with risperidone (81%) and aripiprazole (19%) for disruptive behavioral symptoms in patients with and without neurodevelopmental disorders. Overall, BMI-Z was 1.2 at first and 1.4 at last visit (no significant change). We could design four weight-change trajectories, determined by the factors: drug (risperidone/aripiprazole) and age status (children/adolescent). Additional factors not retained in the model but possibly explanatory include the previous duration of SGA treatment and a progressive patient-selection effect due to dropouts in this observational study. Risperidone treatment was associated with trends of BMI-Z increase in children and decrease in adolescents. Aripiprazole treatment was associated with significant BMI-Z increase, higher in children than in adolescents. Results are probably due to longer previous drug exposure in adolescents.
Children were at risk of weight gain more than adolescents, for both risperidone and, of note, aripiprazole. Adolescents and patients with long previous drug exposure tend to reach stable BMI-Z, although in the range between excessive weight and obesity.
第二代抗精神病药物（SGA）会增加食欲和体重，进而引发代谢综合征。利培酮和阿立哌唑是儿科最常用的SGA，此前主要在短期临床试验中进行研究，其中利培酮会导致体重快速增加，阿立哌唑则使体重增加较慢，而长期影响尚未阐明。尽管基线体重、既往SGA暴露情况、青春期状态和SGA类型被认为是调节因素，但可能影响体重增加的因素同样未得到明确。我们分析了纳入一项为期2年观察性研究的儿科门诊患者样本中，利培酮和阿立哌唑引起的体重增加情况。
我们在多个时间点评估了他们的体重指数（BMI）-Z评分（根据年龄和性别校正并参照全国标准）。我们使用分层混合效应模型来设计BMI-Z轨迹，并观察了几个变量对确定轨迹的影响。
研究组包括127名患者，主要为男性（79%），平均年龄12.6岁，因行为紊乱症状接受利培酮（81%）和阿立哌唑（19%）治疗，患者伴有或不伴有神经发育障碍。总体而言，首次就诊时BMI-Z为1.2，末次就诊时为1.4（无显著变化）。我们可以设计出四种体重变化轨迹，由以下因素决定：药物（利培酮/阿立哌唑）和年龄状态（儿童/青少年）。模型中未保留但可能具有解释作用的其他因素包括既往SGA治疗持续时间以及由于本观察性研究中的患者退出而产生的渐进性患者选择效应。利培酮治疗与儿童BMI-Z升高趋势以及青少年BMI-Z降低趋势相关。阿立哌唑治疗与BMI-Z显著升高相关，儿童升高幅度高于青少年。结果可能是由于青少年既往药物暴露时间更长。
利培酮以及值得注意的阿立哌唑，使儿童比青少年面临更高的体重增加风险。青少年和既往药物暴露时间长的患者往往会达到稳定的BMI-Z，尽管处于超重和肥胖之间的范围。
