Transcript Use of Atypical Antipsychotic Drugs by Children

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,
1993-2000
16000
Prescriptions (x 1000)
14000
12000
10000
Conventional
Atypical
8000
6000
4000
2000
0
1993
1994
1995
1996
1997
Year
Source: Verispan Source Prescription Audit, 1993-2000
1998
1999
2000
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 2001
• 1171 insurance carriers covering all 50 states,
DC, Puerto Rico, and the US Virgin Islands
Data 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 Characteristics
Study Population
(n = 6 213 824)
Characteristic
Male
Female
3 187 077 (51.2)
3 029 747 (48.8)
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)
All
Age, y
Annual Prevalence of the
Use of Atypical Antipsychotics
Characteristic
Subjects with ≥ 1 Claim for an Atypical Antipsychotic
(n = 16 599)
Male
Female
n (%)
Annual
Prevalence*
n (%)
Annual
Prevalence*
11 728 (70.7)
368.3
4871 (29.3)
160.8†
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
All
Age, y†
* Number of subjects per 100 000 with ≥ 1 claim for a drug of interest in 2001.
† P < .0001.
Prevalence of the Use of Atypical
Antipsychotics by Age and Gender
700
600
Prevalence *
Boys
Girls
500
400
300
200
100
0
0 to 4
5 to 9
10 to 14
15 to 19
Age, y
* Number of subjects per 100 000 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 = 16 599)
Male
All
Female
n (%)
Annual
Prevalence*
n (%)
Annual
Prevalence*
11 728 (70.7)
368.3
4871 (29.3)
160.8†
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)
264 (5.4)
8.7†
Clozapine
Concurrent use of
antidepressant
6131 (52.3)
12.5
192.6
3236 (66.3)
* Number of subjects per 100 000 with ≥ 1 claim for a drug of interest in 2001.
† P < .0001.
106.8†
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