Winterfeld U, Le Heuzey M-F, Acquaviva E, Mouren M-C, Brion F, Bourdon O
Pharmacie, hôpital Robert-Debré, AP-HP, université Paris Descartes, Paris, France.
Arch Pediatr. 2009 Sep;16(9):1252-60. doi: 10.1016/j.arcped.2009.06.012. Epub 2009 Jul 28.
The aim of this study was to investigate the use of psychotropic medications for both labeled and off-labeled indications in a French paediatric teaching hospital.
A prospective analysis of all psychotropic drug prescriptions was conducted during a 6-month interval. Details were recorded from the computerized prescription order entry system. They included demographic data (sex, age and weight) and psychotropic medications (name, dosage, schedule, route of administration and indication). The physicians specified the indication when prescribing the psychotropic medication. All prescriptions were assessed for off-label use. Off-label prescriptions were defined as: use of a different dose or dose schedule, use for an indication not included in the license or approved for adults only, drug use outside the age range of the product license, use of medicines for which no paediatric information was available, use when the product was contraindicated, use of drug preparations that were manufactured by the hospital pharmacy, use of licensed drugs that were modified by the hospital pharmacy and use of new drugs available under a special manufacturing license. Each prescription was compared with data available in the National French Formulary.
A total of 1629 drug prescriptions were written for 472 patients. Sixty-eight percent of all drug prescriptions were for off-label uses: indication not included in the license or approved for adults only in 40%, no paediatric information available in 37%, different dose or dose schedule in 7%, licensed drugs that were modified by the hospital pharmacy in 5%, administration to children outside the age range of the product license in 4%, drug preparations that were manufactured by the hospital pharmacy in 4%, contraindication in 2% and new drugs available under a special manufacturing license in 1%. Sixty-six percent of the patients were prescribed a psychotropic drug in an off-label manner. Over half of the off-label prescriptions were given to adolescents (62%), followed by children (29%), infants (8%) and neonates (1%). The percentage of off-label prescriptions by age was: neonates 91%; adolescents 74%; children 59% and infants 58%. The percentage of off-label prescriptions by medication class are presented in decreasing order of prescription frequency: anxiolytics 65%; antipsychotics 69%; antidepressants 92%; antiepileptics 51%; stimulants 30%; antiparkinsonians 100% and hypnotics 100%. The 5 drugs most commonly prescribed off label were risperidone (12%), clobazam (12%), amitriptyline (11%), hydroxyzine (10%) and diazepam (7%). Nearly half (47%) of all off-label prescriptions were associated with 3 indications: anxiety (24%), disruptive behaviour (12%) and pain (11%).
The high rates of off-label prescription documented here and elsewhere highlight the need for further controlled clinical trials to evaluate the risks and benefits of psychotropic medication in children and adolescents.
本研究旨在调查法国一家儿科教学医院中精神类药物用于标签注明适应症和未注明适应症的情况。
对6个月期间所有精神类药物处方进行前瞻性分析。从计算机化处方录入系统记录详细信息。这些信息包括人口统计学数据（性别、年龄和体重）以及精神类药物（名称、剂量、用药时间表、给药途径和适应症）。医生在开具精神类药物处方时注明适应症。评估所有处方的未注明适应症用药情况。未注明适应症处方定义为：使用不同剂量或给药时间表、用于未在药品许可范围内或仅批准用于成人的适应症、在产品许可年龄范围外使用药物、使用无儿科信息的药物、在有禁忌症时使用、使用医院药房生产的药物制剂、使用经医院药房修改的许可药物以及使用根据特殊生产许可提供的新药。将每张处方与法国国家处方集里的可用数据进行比较。
共为472名患者开具了1629张药物处方。所有药物处方中有68%为未注明适应症用药：未在药品许可范围内或仅批准用于成人的适应症占40%，无儿科信息的占37%，不同剂量或给药时间表的占7%，经医院药房修改的许可药物占5%，在产品许可年龄范围外对儿童给药的占4%，医院药房生产的药物制剂占4%，有禁忌症的占2%，根据特殊生产许可提供的新药占1%。66%的患者接受了未注明适应症的精神类药物处方。超过一半的未注明适应症处方开具给了青少年（62%），其次是儿童（29%）、婴儿（8%）和新生儿（1%）。按年龄划分的未注明适应症处方百分比为：新生儿91%；青少年74%；儿童59%；婴儿58%。按药物类别划分的未注明适应症处方百分比按处方频率从高到低排列为：抗焦虑药65%；抗精神病药69%；抗抑郁药92%；抗癫痫药51%；兴奋剂30%；抗帕金森病药100%；催眠药100%。最常被用于未注明适应症的5种药物为利培酮（12%）、氯巴占（12%）、阿米替林（11%）、羟嗪（10%）和地西泮（7%）。所有未注明适应症处方中近一半（47%）与3种适应症相关：焦虑（24%）、破坏性行为（12%）和疼痛（11%）。
此处及其他地方记录的未注明适应症处方的高比例突出表明，需要进一步开展对照临床试验，以评估精神类药物在儿童和青少年中的风险和益处。
