National trends in pediatric use of anticonvulsants: On and off-label

Background. Anticonvulsant (ATC) use for psychiatric disorders in youth dramatically increased during the last decade. This off-label use, particularly by divalproex, is a growing concern because of its doubtful efficacy (Pavuluri MN et al. 2010; Wagner KD, et al. 2006) and safety concerns (Bryant AE, et al. 1996; Wisner et al. 2011). Objectives. To assess 13-year national trends in ATC use for seizure and psychiatric disorders in the pediatric population. Methods. In a cross-sectional design, outpatient visit data were analyzed from the National Ambulatory Medical Care Surveys (NAMCS) and the National Hospital Ambulatory Surveys (NHAMCS). Data were organized by year (1996-1997, 2000-2001, 2004-2005, and 2007-2008). ATC visit records were collected for youth less than 18 years old. Six ATCs were examined: divalproex, oxcarbazepine, carbamazepine, lamotrigine, topiramate, and gabapentin. Diagnoses were identified by ICD-9-CM codes 290.xx-319.xx for psychiatric diagnoses and 345.xx and 780.3 for seizure and convulsion diagnoses, respectively. Concomitant ATC medication patterns were defined by ATC use with two or more of six psychotropic classes: antidepressants, antipsychotics, stimulants, anxiolytics, hypnotics, and alpha-agonists. The main outcome measure was percent prevalence of ATC visits as a proportion of annual U.S. Census data. Measures included total visits, standard error and confidence intervals of percent prevalence. All statistical analyses were conducted with SAS 9.2. Results. Pediatric ATC visits increased two- fold from 0.97% in 1996 to 1.96% in 2008. ATC visits with any psychiatric diagnosis increased two-fold from 34% (95% CI=20-49%) in 1996 to 68% (95% CI=59-77%) in 2005, but decreased to 41% (95% CI=31-51%) in 2008. Concomitant psychotropic use increased more than two-fold from 25% in 1996 to 52% in 2008. The rank order of ATC use in those with a psychiatric disorder throughout all survey years was divalproex (60.1%), carbamazepine (12.5%), lamotrigine (12.3%), oxcarbazepine (10.0%), topiramate (6.6%), and gabapentin (4.4%). Divalproex use has gone from 70.8% in 1996-1997 to 35.2% in 2007-2008. The major psychiatric diagnosis was behavior disorders, which included attention-deficit/hyperactivity disorder and conduct disorder/oppositional defiant disorder. Conclusions. While ATC use for seizure disorders remained stable across 13 years, anticonvulsant use for psychiatric conditions initially rose but then decreased from 2005 to 2008. Nevertheless, concomitant regimens including ATCs have increased steadily over the last decade. With studies disputing the efficacy of ATCs in pediatric patients for psychiatric disorders, the continued off-label use of ATCs in the U.S. remains a concern for both efficacy and safety.