Use of Atypical Antipsychotic Drugs by Children and Adolescents in the United States: A Retrospective Cohort Study Lesley H. Curtis, PhD Center for Clinical and Genetic Economics Duke Clinical Research Institute Duke University Medical Center

Research Team Lesley H. Curtis Leah E. Masselink Truls Østbye Steve Hutchison Peter E. Dans Alan Wright Ranga R. Krishnan Kevin A. Schulman

Funding/Support Supported in part by a Centers for Education and Research on Therapeutics (CERTs) cooperative agreement with the Agency for Healthcare Research and Quality.

Background Pediatric use of psychotropic medications has received considerable attention in scientific literature and news media Documented use of CNS stimulants, SSRIs, tricyclic and other antidepressants, and antipsychotics Most studies predate atypical antipsychotics, but there is evidence of increasing use of these drugs in pediatric populations

Atypical Antipsychotics FDA-approved atypical antipsychotics for treatment of schizophrenia: –risperidone –olanzapine –quetiapine –clozapine –ziprasidone In adults, atypical antipsychotics are at least as efficacious as traditional antipsychotics and have a lower risk of extrapyramidal side effects

Prescriptions for Antipsychotics, Source: Verispan Source Prescription Audit,

Atypical Antipsychotics in Children and Adolescents No atypical antipsychotic drugs are approved for use in pediatric populations Data supporting safety and efficacy of atypical antipsychotics for children and adolescents are limited –9 randomized controlled trials in children aged 10 years and younger –small sample sizes (≤ 120 patients) –short follow-up (≤ 10 weeks)

Atypical Antipsychotics in Children and Adolescents Adverse effects (ie, weight gain, sedation, and extrapyramidal symptoms) may be more prevalent and more severe in children and adolescents than in adults

Study Objective To examine the use of atypical antipsychotic drugs by children and adolescents in a large national database of prescription drug claims for patients with prescription drug insurance

Data Source Outpatient prescription claims database of AdvancePCS –Largest pharmaceutical benefit manager in the United States, covering 30 million lives –More than 98% of claims processed electronically at point of sale

Study Population Individual-level claims Subjects aged ≤ 19 years and enrolled continuously throughout 2001 Subjects filed at least 1 claim for any prescription drug in insurance carriers covering all 50 states, DC, Puerto Rico, and the US Virgin Islands

Data Analysis “Annual Prevalence” Number of children and adolescents per with at least 1 prescription drug claim for a drug of interest in 2001 Calculated annual prevalence for each atypical antipsychotic drug individually Also calculated annual prevalence for concurrent use of antidepressant drugs

Data Analysis (cont.) Stratified by gender to explore gender differences in the use of atypical antipsychotics Used chi-square or Fisher exact tests to test for differences in proportions and prevalence rates

Subject Characteristics Characteristic Study Population (n = ) MaleFemale All (51.2) (48.8) Age, y 0 to (22.7) (22.6) 5 to (26.0) (25.9) 10 to (26.5) (26.5) 15 to (24.9) (25.1)

Annual Prevalence of the Use of Atypical Antipsychotics Characteristic Subjects with ≥ 1 Claim for an Atypical Antipsychotic (n = ) MaleFemale n (%) Annual Prevalence*n (%) Annual Prevalence* All (70.7) (29.3)160.8† Age, y† 0 to 4223 (1.9) (1.0)7.0 5 to (23.9) (15.6) to (42.7) (38.0) to (31.5) (45.4)291.0 * Number of subjects per with ≥ 1 claim for a drug of interest in † P <.0001.

Prevalence of the Use of Atypical Antipsychotics by Age and Gender * Number of subjects per with ≥ 1 claim for an atypical antipsychotic in 2001.

Annual Prevalence of the Use of Atypical Antipsychotics by Drug Characteristic Subjects with ≥ 1 Claim for an Atypical Antipsychotic (n = ) MaleFemale n (%) Annual Prevalence*n (%) Annual Prevalence* All (70.7) (29.3)160.8† Clozapine58 (0.5)1.827 (0.6)0.9† Olanzapine3151 (27.1) (28.1)45.2† Quetiapine1849 (16.1) (25.8)41.5† Risperidone8121 (69.4) (61.2)98.4† Ziprasidone398 (3.5) (5.4)8.7† Concurrent use of antidepressant6131 (52.3) (66.3)106.8† * Number of subjects per with ≥ 1 claim for a drug of interest in † P <.0001.

Limitations Filed claims, not drugs actually taken Does not capture out-of-pocket payments or alternative sources of payment Persons of lower socioeconomic status may be underrepresented Clinical variables not directly available in data set

Importance Increasing use of atypical antipsychotics Long-term effects of early and prolonged exposure are unknown; data in pediatric populations are limited Preliminary evidence that side effects may be more common and more severe in children

Relevance to Clinical Practice Off-label use of prescription drugs in children and adolescents is common, despite lack of data Primary care physicians may be more likely than pediatric psychopharmacologists to prescribe psychotropic drugs Implications for safety and efficacy of extrapolating from adult dosages and schedules?

Relevance to Policy Medicaid provides coverage for drug therapy but limited reimbursement for psychiatric evaluation Incentive to treat behavioral problems using drug therapy?

Relevance to Health Services Research Potential for using large PBM databases for postmarketing surveillance of prescription drugs Potential to examine “real-time” use of prescription drugs May also be useful for exploring associations observed in case reports

Relevance to Health Services Research However, must move beyond claims data toward understanding the clinical circumstances