Use of Atypical Antipsychotic Drugs by Children Use of Atypical Antipsychotic Drugs by Children and Adolescents in the United States:and Adolescents in the United States:

A Retrospective Cohort StudyA Retrospective Cohort Study

Lesley H. Curtis, PhDLesley H. Curtis, PhD

Center for Clinical and Genetic EconomicsCenter for Clinical and Genetic EconomicsDuke Clinical Research InstituteDuke Clinical Research InstituteDuke University Medical CenterDuke 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.

BackgroundBackground

• 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 AntipsychoticsAtypical 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,1993-2000

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12000

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16000

1993 1994 1995 1996 1997 1998 1999 2000

Year

Pre

sc

rip

tio

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(x

10

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Conventional Atypical

Source: Verispan Source Prescription Audit, 1993-2000

Atypical Antipsychotics inAtypical Antipsychotics inChildren and AdolescentsChildren 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 inAtypical Antipsychotics inChildren and AdolescentsChildren 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 2001• 1171 insurance carriers covering all 50 states,

DC, Puerto Rico, and the US Virgin Islands

Data AnalysisData Analysis

“Annual Prevalence”

• Number of children and adolescents per 100 000 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 CharacteristicsSubject Characteristics

CharacteristicStudy Population

(n = 6 213 824)

Male Female

All 3 187 077 (51.2) 3 029 747 (48.8)

Age, y

0 to 4 722 971 (22.7) 683 352 (22.6)

5 to 9 826 626 (26.0) 784 492 (25.9)

10 to 14 842 486 (26.5) 802 853 (26.5)

15 to 19 791 994 (24.9) 759 050 (25.1)

Annual Prevalence of theAnnual Prevalence of theUse of Atypical AntipsychoticsUse of Atypical Antipsychotics

CharacteristicSubjects with ≥ 1 Claim for an Atypical Antipsychotic

(n = 16 599)

Male Female

n (%)Annual

Prevalence* n (%)Annual

Prevalence*

All 11 728 (70.7) 368.3 4871 (29.3) 160.8†

Age, y†

0 to 4 223 (1.9) 30.8 48 (1.0) 7.0

5 to 9 2798 (23.9) 338.5 761 (15.6) 97.0

10 to 14 5007 (42.7) 594.3 1853 (38.0) 230.8

15 to 19 3700 (31.5) 467.2 2209 (45.4) 291.0

* Number of subjects per 100 000 with ≥ 1 claim for a drug of interest in 2001.† P < .0001.

Prevalence of the Use of Atypical Prevalence of the Use of Atypical Antipsychotics by Age and GenderAntipsychotics by Age and Gender

0

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700

0 to 4 5 to 9 10 to 14 15 to 19

Age, y

Pre

va

len

ce

*

Boys Girls

* Number of subjects per 100 000 with ≥ 1 claim for an atypical antipsychotic in 2001.

Annual Prevalence of the Use ofAtypical Antipsychotics by Drug

CharacteristicSubjects with ≥ 1 Claim for an Atypical Antipsychotic

(n = 16 599)

Male Female

n (%)Annual

Prevalence* n (%)Annual

Prevalence*

All 11 728 (70.7) 368.3 4871 (29.3) 160.8†

Clozapine 58 (0.5) 1.8 27 (0.6) 0.9†

Olanzapine 3151 (27.1) 99.0 1369 (28.1) 45.2†

Quetiapine 1849 (16.1) 58.1 1257 (25.8) 41.5†

Risperidone 8121 (69.4) 255.1 2980 (61.2) 98.4†

Ziprasidone 398 (3.5) 12.5 264 (5.4) 8.7†

Concurrent use of antidepressant 6131 (52.3) 192.6 3236 (66.3) 106.8†

* Number of subjects per 100 000 with ≥ 1 claim for a drug of interest in 2001.† 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