Therapies for Children With Autism Spectrum Disorders

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Evidence Table. Therapies for children with ASD (continued) Study Inclusion/ Exclusion Baseline Description Intervention Criteria/ Population Measures Outcomes 2009 week 1, increased to 5 diagnosis (DSMIV, ADI- mean (SE): LOCF, mean Country: mg/day for week 2 and R) and demonstrated G1a: 5.0 (0.1) change (SE): US increased in 5 mg tantrums, aggression, (n=44) G1a: -0.9 (0.2) Practice increments until assigned self-injurious behavior, G1b: 4.9 (0.1) (n=44) setting: daily dose (5, 10, 15 or combination (n=52) G1b: -1.0 (0.1) Pharmaceutical mg/day) reached • CGI-S score ≥ 4 at G1c: 5.1 (0.1) (n=52) company Assessments: screening and baseline (n=44) G1c: -1.1 (0.2) Intervention ABC rated by caregiver at • ABC irritability score G2: 4.7 (0.1) (n=44) setting: each visit; CGI-severity ≥ 18 at screening and (n=41) G2: -0.6 (0.2) Multi-site clinics and improvement rated by baseline Social skills: (n=41) Enrollment clinician at each visit, Yale • Weight ≥ 15 kg ABC lethargy/social G1a/G2: P = NS period: Brown Obsessive Com- • Age 6-17 yrs withdrawal score, G1b/G2: P ≤ 0.05 June 2006 to June pulsion Scale (compulsion Exclusion criteria: LOCF, mean (SE): G1c/G2: P = ≤ 2008 scale only, weeks 0,4,8), Current diagnosis of G1a: 17.7 (1.4) 0.05 Funding: administrator/rater NR; bipolar disorder, (n=52) Response rate, Bristol Myers Pediatric QoL Inventory, psychosis, G1b: 16.8 (1.3) week 8, n (%) Sqibb, Otsuka Caregiver Strain schizophrenia, major (n=59) G1a: 29 (55.8) Pharmaceutical Questionnaire assessed depression, or fragile X G1c: 18.9 (1.4) (n=52; P ≤ 0.05) Co. at baseline and week 8. syndrome (n=53) G1b: 29 (49.2) Author industry Simpson-Angus Scale, • Diagnosis of another G2: 18.0 (1.5) (n=59; P = NS) relationship Barnes Akathisia Rating disorder on the autism (n=49) G1c: 28 (52.8) disclosures: Scale, Abnormal spectrum including PDD- Repetitive (n=53; P = NS) 5 of 7 Involuntary Movement NOS, Asperger behavior: G2:17 (34.7) Bristol-Myers Scale used by clinician to syndrome, Rett ABC stereotypy (n=49; P = NS) Squibb (5) rate adverse events syndrome, or childhood score, LOCF, mean Social skills: Forest (1) Groups: disintegrative disorder (SE): ABC lethargy/ Johnson & G1a: aripiprazole 5 • History of neuroleptic G1a: 11.4 (0.8) social withdrawal Johnson (1) mg/day malignant syndrome (n=52) score, week 8, Otsuka (2) G1b: aripiprazole 10 • Significant risk for G1b: 11.6 (0.8) LOCF, mean Design: mg/day suicide (N=59) change (SE): RCT, multicenter G1c: aripiprazole 15 G1c: 11.6 (0.8) G1a: -5.8 (1.2) • Seizure in past year study mg/day (n=53) (n=52) • History of severe head Note: G2: placebo G2: 10.7 (0.8) G1b: -4.9 (1.1) trauma or stroke See related study Co-interventions held (n=49) (n=59) Owen et al. 2009 stable during treatment: • History or evidence of Problem behavior: G1c: -7.9 (1.1) ({#5714}) All psychotropic unstable medical ABC hyperactivity (n=53) medications discontinued conditions score, LOCF, mean G2: -5.2 (1.2) prior to study; sleep aids, • Clinically significant lab (SE): (n=49) anti-anxiety medication or diagnostic test result G1a: 33.1 (1.4) G1a/G2: P = NS diphenhydramine, • Demonstrated resistance (n=52) G1b/G2: P = NS psychotropic medications to antipsychotic G1b: 33.7 (1.3) G1c/G2: P = NS for acute treatment of medication or allergy/ (n=59) unforeseen events, hypersensitivity to G1c: 32.2 (1.4) benztropine, propranolol aripiprazole (n=53) administered at • Unstable/inconsistent G2: 31.0 (1.4) investigators discretion non-pharmacologic (n=49) Frequency of contact therapies during study: Age, years ± SD: Weekly clinic visits; tele- G1a: 9.0 ± 2.8 phone contact at week 7 G1b: 10.0 ± 3.2 G1c: 9.5 ± 3.1 G2: 10.2 ± 3.1 Marcus et al., Concomitant therapies, Mental age: Communication/ Communication/ 2009 %: NR language: language: (continued) Analgesics and Gender, n (%): ABC inappropriate ABC inappropriate antipyretics: Male: speech score, speech score, G1a: 23.1 G1a: 47 (88.7) LOCF, mean (SE): week 8, LOCF, G1b: 30.2 G1b: 50 (84.7) G1a: 5.8 (0.6) mean (SE): C-68
Evidence Table. Therapies for children with ASD (continued) Study Inclusion/ Exclusion Description Intervention Criteria/ Population G1c: 22.2 G1c: 50 (92.6) G2: 17.6 G2: 48 (92.3) Anticholinergics: Race/ethnicity, n (%): G1a: 3.8 White: G1b: 1.7 G1a: 37 (69.8) G1c: 9.3 G1b: 41 (69.5) G2: 0 G1c: 42 (77.8) Anxiolytics: G2: 35 (67.3) G1a: 3.8 Black: G1b: 1.7 G1a: 13 (24.5) G1c: 1.9 G1b: 15 (25.4) G2: 5.9 G1c: 9 (16.7) Hypnotics and sedatives: G2: 13 (25.0) G1a: 3.8 Asian: G1b: 1.7 G1a: 1 (1.9) G1c: 1.9 G1b: 2 (3.4) G2: 3.9 G1c: 0 Propranolol: G2: 3 (5.8) G1a: 3.8 Other: G1b: 0 G1a: 2 (3.8) G1c: 0 G1b: 1 (1.7) G2: 2.0 G1c: 3 (5.6) N at enrollment: G2: 1 (1.9) G1a: 53 SES: G1b: 59 Maternal education: NR G1c: 54 Household income: NR G2: 52 Diagnostic approach: N at follow-up: In Study G1a: 44 Diagnostic tool/method: G1b: 49 ADI-R G1c: 47 Diagnostic category, %: G2: 38 Autistic disorder: G1: 100 G2: 100 Other characteristics: Weight, kg mean ± SD: G1a: 38.9 ± 18.3 G1b: 44.8 ± 22.4 G1c: 42.2 ± 23.0 G2: 45.6 ± 20.0 Marcus et al., 2009 (continued) Previous psychotropic medication, n (%): Any nervous system: G1a: 24/52 (46.2) G1b: 32/59 (54.2) G1c: 31/54 (57.4) G2: 22/51 (43.1) Any psychotic: C-69 Baseline Measures Outcomes (n=52) G1b: 6.8 (0.5) (n=59) G1c: 6.3 (0.5) (n=53) G2: 5.9 (0.6) (n=48) CY-BOCS compulsions score, LOCF, mean (SE): G1a: 13.9 (0.6) (n=52) G1b: 13.5 (0.5) (n=59) G1c: 14.1 (0.5) (n=53) G2: 13.7 (0.6) (n=48) Other: Serum prolactin, ng/mL: G1a: 7.2 G1b: 6.5 G1c: 6.7 G2: 6.9 Weight, kg, mean (SE): G1a: 39.0 (3.1) G1b: 45.2 (2.9) G1c: 42.3 (3.0) G2: 46.3 (3.2) BMI, kg/m 2 G1a: -2.0 (0.5) (n=52) G1b: -1.8 (0.4) (n=59) G1c: -2.3 (0.4) (n=53) G2: -1.1 (0.5) (n=48) G1a/G2: P = NS G1b/G2: P = NS G1c/G2: P ≤ 0.05 Repetitive behavior: ABC stereotypy score, 8 weeks. LOCF, mean change (SE): G1a: -4.5 (0.68) (n=52) G1b: -4.2 (0.63) (n=59) G1c: -4.5 (0.66) (n=53) G2: -1.8 (0.69) (n=49) G1a/G2: P ≤ 0.005 G1b/G2: P ≤ 0.05 G1c/G2: P ≤ , mean 0.005 Problem (SE): behavior: G1a: 20.2 (1.0) ABC hyperactivity G1b: 21.1 (1.0) score, 8 weeks, G1c: 20.8 (1.0) LOCF, mean G2: 21.0 (1.1) change(SE): QTcF interval, G1a: -14.0 (1.6) milliseconds: mean: (n=52) G1a: 373.5 G1b: -13.3 (1.5) G1b: 380.2 (n=59) G1c: 378.2 G1c: -16.3 (1.6) G2: 384.6 (n=53) G2: -7.7 (1.7) (n=49) G1a/G2: P ≤ 0.005 G1b/G2: P ≤ 0.05 G1c/G2: P ≤ 0.001 CY-BOCS compulsions, 8 weeks, LOCF, mean change (SE): G1a: -2.6 (0.5) (n=52) G1b: -2.4 (0.4) (n=59)
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Comparative Effectiveness Review Nu
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This report is based on research co
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Acknowledgments We are indebted to
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Therapies for Children With Autism
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Dietary and Other Medical Intervent
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Figures Figure A. Analytic framewor
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Table A. Description of interventio
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Analytic Framework Figure A. Analyt
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Strength of evidence. The degree of
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epetitive behavior showed improveme
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subgroups of children, although the
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We encourage investigators to provi
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9. Remington B, Hastings RP, Kovsho
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46. Green J, Charman T, McConachie
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82. Reaven JA, Blakeley-Smith A, Ni
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120. Masi G, Cosenza A, Mucci M, et
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157. Evangeliou A, Vlachonikolis I,
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Introduction Need for Evidence for
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Interventions intended primarily to
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Table 1. Description of behavioral
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Serotonin reuptake inhibitors. Sero
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Table 3. Description of medical and
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Table 4. Description of allied heal
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Key Questions and Analytic Framewor
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Chapter 4 discusses the results in
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Methods This chapter documents proc
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• Did not present aggregated resu
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Additional behavioral interventions
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1. Did the study employ a group des
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Scoring: Studies minimally had to h
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These ratings of applicability do n
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Figure 2. Disposition of articles a
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• ABA-based approaches including
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education, children in the intensiv
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abilities. This finding is further
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Table 10. Outcomes of early intensi
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forecast behavior; perspective taki
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interaction with peers; outcome mea
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hyperactivity, inattention, challen
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Table 12. Outcomes of RCTs assessin
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Schedule for Affective Disorders an
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SCAS-P=Spence Child Anxiety Scale-P
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Summary of the literature. Jarusiew
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Table 14. Overview of educational s
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on the Ankara Developmental Screeni
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Checklist scores decreased by 8.4 f
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Table 15. Outcomes of studies asses
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evaluated the effects of risperidon
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that this somnolence improved over
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Table 17. Outcomes of RCTs of antip
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Serotonin Reuptake Inhibitors SRIs
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One prospective case series of esci
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Most participants were recruited fr
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Dietary and Other Medical Intervent
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Summary of the literature-other int
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withdrew after the first six weeks;
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therefore described separately belo
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addressed, 85 typically involves on
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In the second paper, 89 treatment s
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Table 25. Overview of CAM studies a
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Teacher and Parent Scales, behavior
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Because of the potentially increase
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Educational Interventions Child cha
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showed diminished response to escit
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oom as the other assessments, so it
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contrast group (n=18) on three meas
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and are based on consideration of f
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Few studies directly comparing the
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Strength of evidence. The strength
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While individual studies of CBT and
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Table 32. Summary of results of edu
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Table 33. Summary of results of med
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strength of this reviewed literatur
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Table 36. Intervention, strength of
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Table 37. Interventions/outcomes wi
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gains. 104 Other studies have seen
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percent of behavioral studies repor
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limited followup, lack of comparati
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individual intervention is warrante
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selecting participants for their st
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studies lacked an arm that consider
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23. Kanner L. Autistic Disturbances
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62. Dosman CF, Drmic IE, Brian JA,
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104. Ben-Itzchak E and Zachor DA. T
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142. Tyminski RF and Moore PJ. The
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177. Aman MG, McDougle CJ, Scahill
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214. Correia CT, Almeida JP, Santos
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252. Akhondzadeh S, Tajdar H, Moham
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290. Dawson G, Rogers S, Munson J,
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Acronyms/Abbreviations ABA Applied
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Appendix A. Exact Search Strings an
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Table A2. PsycINFO search strategie
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Therapies for Children with Autism
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Therapies for Children with ASD Sys
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Appendix C. Evidence Tables Tables
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Evidence Table. Therapies for child
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Country: US Practice setting: Clini
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Dunn-Geier et al., 2000 (continued)
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Evidence Table: Therapies for Child
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Appendix D. List of Excluded Studie
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31. Aarsland D, Cummings JL and Lar
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59. Ahearn WH, Clark KM, Gardenier
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89. Allison DB, Basile VC and MacDo
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118. Ando H, Yoshimura I and Wakaba
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146. Atkinson RP, Jenson WR, Rovner
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177. Bakare MO, Agomoh AO, Ebigbo P
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233. Bebko JM, Perry A and Bryson S
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262. Bergmann F, Stepp H, Metzger R
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291. Birkan B, McClannahan LE and K
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319. Boddy F, Rowan EN, Lett D, et
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348. Bouma R and Schweitzer R. The
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376. Broadstock M, Doughty C and Eg
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404. Brudnak MA. Application of gen
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432. Buitelaar JK. Why have drug tr
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460. Butler DE, Nordin IC, L’Ital
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489. Campbell M, Locascio JJ, Choro
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517. Caronna EB, Augustyn M and Zuc
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546. Case-Smith J and Miller H. Occ
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574. Charlop MH, Burgio LD, Iwata B
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602. Cheng CW, Cho SH, Taylor M, et
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662. Collier D and Reid G. A compar
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691. Coskun M, Karakoc S, Kircelli
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718. Cullen LA, Barlow JH and Cushw
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748. Davidovitch M, Holtzman G and
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805. Devlin SD, Harber MM. Collabor
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834. Doherty K, Fitzgerald M and Ma
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863. Dudley LL, Johnson C and Barne
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893. Dybvik AC. Autism and the Incl
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924. Elder JH. In-home communicatio
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953. Erickson CA, Posey DJ, Stigler
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1008. Ferri R, Elia M, Agarwal N, e
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1037. Fisher W, Kerbeshian J and Bu
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1095. Furneaux B. Keeping the balan
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1124. Garcaa-Villamisar D, Wehman P
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1152. Ghezzi PM. Discrete Trials Te
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1180. Goin-Kochel RP, Myers BJ and
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1210. Gordon R, Handleman JS and Ha
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1239. Grimaldi BL. The central role
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1296. Hamdan-Allen G. Brief report:
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1324. Hare DJ, Jones JPR and Paine
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1356. Harrison S and Berry L. Valui
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1386. Heilbrun AB, Jr., Blum N and
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1414. Hetzroni OE and Shalem U. Fro
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1443. Holburn CS. Counter the mistr
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1473. Horner RH, Carr EG, Strain PS
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1504. Hughes C, Soares-Boucaud I, H
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1533. Ijichi S and Ijichi N. Beyond
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1562. James SJ, Cutler P, Melnyk S,
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1591. Johnson CR, Butter EM, Handen
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1619. Joyce PR. The medical model-w
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1647. Karmali I, Greer RD, Nuzzolo-
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1702. Kielinen M, Linna SL and Moil
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1731. Klin A, Lin DJ, Gorrindo P, e
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1790. Kolmen BK, Feldman HM, Handen
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1819. Kratochvil CJ, Findling RL, M
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1846. Lam MK and Rao N. Developing
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1874. Lattimore LP, Parsons MB and
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1903. Lee PC. Verification of a sim
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1932. Lerman DC, Vorndran C, Addiso
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1960. Licciardello CC, Harchik AE a
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1989. Liptak GS, Orlando M, Yinglin
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2015. Lorimer PA, Simpson RL, Myles
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3173. Smith C, Felce D, Jones E, et
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3202. Snyder A, Bossomaier T and Mi
Page 831 and 832:
3230. Spero MH. The emancipation of
Page 833 and 834:
3259. Stephens CE. Spontaneous imit
Page 835 and 836:
3289. Strambi M, Longini M, Hayek J
Page 837 and 838:
3318. Suzumura K. How an autistic b
Page 839 and 840:
3346. Tager-Flusberg H and Calkins
Page 841 and 842:
3376. Taylor I, O’Reilly M and La
Page 843 and 844:
3407. Thunberg G, Ahlsen E and Sand
Page 845 and 846:
3435. Trembath D, Balandin S, Toghe
Page 847 and 848:
3464. Turner-Brown LM, Perry TD, Di
Page 849 and 850:
3492. Van Der Putt R, Dineen C, Jan
Page 851 and 852:
3522. Vitiello B. Recent NIMH clini
Page 853 and 854:
3553. Walenski M, Mostofsky SH, Gid
Page 855 and 856:
3581. Weber RC and Thorpe J. Teachi
Page 857 and 858:
3610. Wheeler JJ, Baggett BA, Fox J
Page 859 and 860:
3637. Williams B. Mental handicap n
Page 861 and 862:
3669. Wimpory D, Chadwick P and Nas
Page 863 and 864:
3698. Worth S and Reynolds S. The A
Page 865 and 866:
3728. Young JM, Krantz PJ, McClanna
Page 867 and 868:
3759. Zuddas A, Di Martino A, Mugli
Page 869 and 870:
Appendix F. Approach to Categorizin
Page 871 and 872:
APPENDIX G. Discussion of Recent Sy
Page 873 and 874:
one a casein free regime. Diets wer
Page 875 and 876:
outcome data as Type 6, defined as
Page 877 and 878:
Yes—no disclosures to make G7 Bai
Page 879 and 880:
Table G1. Characteristics of recent
Page 881 and 882:
Random assignment Appropriate compa
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Page 887 and 888:
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Page 891 and 892:
Page 893 and 894:
Study Group design Random assignmen
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Page 899 and 900:
Page 901 and 902:
Page 903 and 904:
Page 905 and 906:
APPENDIX I. Applicability Summary T
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Social skills (continued) Domain De
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Therapies for Children With Autism Spectrum Disorders

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