Therapies for Children With Autism Spectrum Disorders

Evidence Table. Therapies for children with ASD (continued)
Study
Description Intervention
Author:
Owen et al., 2009
Country:
US
Practice
setting:
Pharmaceutical
company
Intervention
setting:
Multi-site clinics
Enrollment
period:
June 2006 to
February 2008
Funding:
Bristol Myers
Sqibb, Otsuka
Pharmaceutical
Co.
Author industry
relationship
disclosures:
8 of 8
Abbott (1)
Addrenex (1)
Astra Zeneca (1)
Bristol Myers
Squibb (6)
Curemark (1)
Forest (1)
GlaxoSmithKline
(1)
Janssen (1)
Johnson &
Johnson (1)
KemPharm (1)
Lilly (2)
Lundbeck (1)
Neuropharm (2)
Novartis (1)
Organon (1)
Otsuka (4)
Pfizer (2)
Sanofi-Aventis (1)
Seaside Pharma
(1)
Sepracore (1)
Shire (1)
Solvay (1)
Intervention: An 8 week
treatment phase with
Aripiprazole, 2 mg/day
with target dosage of
5,10, or 15 mg/day
(maximum 15 mg/day)
Assessments:
ABC rated by caregiver at
each visit; CGI severity
and improvement rated by
clinician at each visit, CY-
BOCS (compulsion scale
only, weeks 0, 4, and 8),
administrator/rater NR;
Pediatric QoL Inventory,
Caregiver Strain
Questionnaire assessed
at baseline and week 8.
Simpson-Angus
Scale, Barnes Akathisia
Rating Scale, Abnormal
Involuntary Movement
Scale used by clinician to
rate adverse events
Groups:
G1: aripiprazole
G2: placebo
Co-interventions held
stable during treatment:
All psychotropic
medications discontinued
prior to study; lorazepam
or alprazolam, sleep aids,
diphenhydramine,
benztropine, propranolol
administered at
investigators discretion
Frequency of contact
during study:
Weekly clinic visits; telephone
contact at week 7
Concomitant therapies,
%:
Analgesics/anti-pyretics:
G1: 19.1
G2: 22.0
Hypnotics/sedatives:
G1: 2.1
G2: 12.0
N at enrollment:*
Inclusion/ Exclusion
Criteria/ Population
Inclusion criteria:
• Autistic disorder
diagnosis (DSM-IV, ADI-
R) and demon-strated
tantrums, aggression,
self- injurious behavior,
or a combination thereof
• CGI-S score ≥ 4 at
screening and baseline
• ABC irritability score
≥ 18 at screening and
baseline
• Weight ≥ 15 kg
• Age 6-17 years
Exclusion criteria:
• Current diagnosis of
bipolar disorder, psychosis,
schizophrenia,
major depression, or
fragile X syndrome
• Diagnosis of another
disorder on the autism
spectrum including PDD-
NOS, Asperger
syndrome, Rett
syndrome, or childhood
disintegrative disorder
• History of neuroleptic
malignant syndrome
• Significant risk for
suicide
• Seizure in past year
• History of severe head
trauma or stroke
• History or evidence of
unstable medical
conditions
• Clinically significant lab
or diagnostic test result
• Demonstrated resistance
to antipsychotic
medication or allergy/
hypersensitivity to
aripiprazole
• Unstable/inconsistent
non-pharmacologic
therapies
Age 6-17y, mean ± SD:
G1: 9.7 ± 3.2
C-74
Baseline
Measures Outcomes
G1c: -4.4
G2: -2.0
G1a/G2: P = NS
G1a/G2: P = NS
G1a/G2: P = NS
Modifiers:
NR
Overall ratings:*
CGI-S, mean:
G1: 4.9 (n=40)
G2: 4.8 (n=40)
Serum prolactin,
ng/ml, mean:
G1: 9.8
G2: 6.8
QTcF interval,
milliseconds, mean:
G1: 377.6
G2: 376.3
Social skills:
ABC lethargy/social
withdrawal score,
mean:
G1: 19.9
G2: 18.1
Communication/
language:
ABC inappropriate
speech score,
mean:
G1: 7.0
G2: 7.0
Repetitive
behavior:
ABC stereotypy
score, mean:
G1: 11.9
G2: 10.7
Problem behavior:
ABC irritability
score, mean:
G1: 29.6
G2: 30.8
ABC hyperactivity
score, mean:
G1: 34.1
G2: 34.7
CY-BOCS score
(compulsions only),
mean:
G1: 12.8 (n=43)
G2: 13.7 (n=44)
Overall ratings:
CGI-I at week 8,
LOCF, efficacy
sample, %:
Very much/much
improved:
G1: 67
G2: 16
Minimally
improved:
G1: 15
G2: 20
No change:
G1:13
G2:45
Minimally worse:
G1:4
G2:10
Much/very much
worse:
G1: 0
G2: 8
CGI-I score, week
8, mean:
G1: 2.2
G2: 3.6
G1/G2: P < 0.001
LSQ mean treatment
difference
(95% CI):
-1.4 (-1.9,-1.0)
CGI-S, week 8,
mean change:
G1: -1.2 (n=40)
G2: -0.4 (n=40)
G1/G2: P < 0.001
LSQ mean treatment
difference
(95% CI):
-0.8 (-1.2,-0.4)
Serum prolactin,
ng/ml, week 8,
mean change:
G1: -6.3
G2: 1.6
G1/G2: P < 0.001
Weight gain, week
8, %
G1: 28.9
G2: 6.1