Therapies for Children With Autism Spectrum Disorders

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Table 20. Outcomes of studies of stimulants for the treatment of hyperactivity in ASDs Author, year, country Groups, N enrollment / N final Study quality RUPP, 228 Posey et al. 229 & Jahromi et al. 230 2005, 2007, & 2009, US Total N=66 G1: low dose MPH (n=45) G2: medium dose MPH (n=52) G3: high dose MPH (n=33) G4: optimal dose MPH (n=58) G5: placebo (n=46) Mean age, years ± SD 7.5 ± 2.2 Mean IQ ± SD Slosson IQ: 62.6 ± 32.9 Outcome measure/ Baseline scores, mean ± SD Teacher ABC- Hyperactivity: 30.9 ± 7.9 72 Outcome measure/Posttreatment scores a , mean ± SD G1: 22.9 ± 12.8, p=0.03 G2: 23.6 ± 12.5, p=0.008 G3: 20.3 ± 11.9, p=0.002 G4: 20.1 ± 12.4, p
Dietary and Other Medical Interventions Additional studies in the medical literature addressed the use of dietary interventions (including special diets) as well as medical therapies for sleep and gastrointestinal dysfunction, hyperbaric oxygen, and other agents. Content of the literature-dietary interventions. We identified eight studies conducted in the clinic setting that addressed the use of various oral dietary supplements to treat ASDs in children, including ages ranging from one to 18 years; interventions included iron, 242 magnesium-vitamin B6, 243 melatonin, 244 ketogenic diet, 245 and fish oil and evening primrose oil. 246 Two studies focused on amino acid derivatives, including L-carnosine 247 and N,N dimethylglycine, 248 and one on a digestive enzyme supplement. 249 Studies measured a wide range of outcomes, with little overlap in instruments utilized among the studies. Most studies analyzed outcomes after 18 days to 3 months; 242,246-249 one study assessed outcomes after 6 months, 245 one study after a mean of eight months, 243 and one examined data at a mean of 1.8 years of followup. 244 Five studies reported adverse events. 242,245,248-250 Table 17 includes additional study information. Summary of the literature-dietary interventions. Two RCTs explored dietary supplementation with amino acid derivatives in ASDs. The 8-week RCT of daily L-carnosine supplementation was conducted at a specialty clinic and included 31 children ages three to twelve years with ASDs. 247 Significant changes on the CGI at 2 weeks compared with 6 weeks were observed in the L-carnosine group; significant effects on receptive vocabulary and GARS scores were also observed before vs. after treatment in this group. However, no significant changes were observed between groups in the Gilliam Autism Rating Scale measure of ASDs severity, Receptive and Expressive Picture Vocabulary scores, or parent-rated CGI measure of overall improvement. Adverse effects in the L-carnosine group included sporadic hyperactivity and were alleviated by dose reduction. The 4-week randomized controlled trial of daily N,N-dimethylglycine treatment was conducted at an academic clinic and included 37 children with ASDs ages three to eleven years. 248 The dimethylglycine group did not improve more than the placebo group on any behavioral measure (VABS, ABC-C). There was no significant effect on neurologic examination of motor skills, muscle tone, or coordination. Adverse effects in the dimethylglycine group were similar to placebo. A six month, double blind, crossover RCT of a digestive enzyme supplement (Peptizyde) which combines the enzymes peptidase, protease 4.5, and papain, included 43 children between the ages of 3 and 8 years (mean= 69.4 months). 249 Most participants (84 percent) were diagnosed with autistic disorder. Participants were randomized to either enzyme for three months followed, after a one-week washout period, by placebo (n=21) or placebo for three months (one-week washout period) followed by enzyme (n=22). Sixteen participants (10 in the enzyme/placebo group and 6 in placebo/enzyme) dropped out of the study for reasons including a parentperceived increase in negative behavior and child refusal to eat food with contents of enzyme capsules added. In intention to treat analyses, investigators reported significant differences between enzyme and placebo only on a measure of food selectivity, which was not sustained over the study period. Investigators noted no serious adverse effects though four children withdrew from the study because of behavioral deterioration perceived by parents. The authors also assessed potential effects of alternative therapies, multivitamins, prescription medications, 73
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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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Page 145 and 146: strength of this reviewed literatur
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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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204. Baron-Cohen S, Scott FJ, Allis
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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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631. Cicero FR and Pfadt A. Investi
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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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777. DeLeon IG, Fisher WW and Marhe
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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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979. Faja S, Aylward E, Bernier R,
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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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1066. Fragala-Pinkham M, Haley SM a
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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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1268. Guptill JT, Booker AB, Gibbs
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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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1673. Kelly AB, Garnett MS, Attwood
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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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1761. Koegel RL and Frea WD. Treatm
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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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2043. Luiselli JK, Kane A, Treml T,
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2071. MacFarlane JR and Kanaya T. W
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2099. Malone RP, Maislin G, Choudhu
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2127. Marin FZ. CAM versus nucleopl
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2157. Martineau J, Roux S, Adrien J
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2185. Matson JL and Lo Vullo SV. A
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2213. McCabe H. The Importance of P
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2240. McDougle CJ, Holmes JP, Carls
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2267. McHale SM, Olley JG, Marcus L
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2296. Merlo LJ, Lehmkuhl HD, Geffke
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2325. Minderaa RB, Anderson GM, Vol
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2354. Montgomery JM, Duncan CR and
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2385. Morrison RS, Sainato DM, Benc
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2413. Munesue T, Ono Y, Mutoh K, et
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2445. Napolitano DA, Tessing JL, Mc
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2474. Niederhofer H and Pittschiele
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2501. Nwora AJ and Gee BM. A case s
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2530. Olive ML, Lang RB and Davis T
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2559. Owens JA, Rosen CL and Mindel
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2589. Pansegrouw I and Alant E. Com
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2618. Paul C, Williams KE, Riegel K
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2646. Perry R, Nobler MS and Campbe
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2675. Piazza CC, Hagopian LP, Hughe
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2704. Poon L, Partika N and Bolman
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2734. Prizant BM. Speech-language p
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2764. Rapp JT, Vollmer TR, St. Pete
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2792. Reed P, Broomfield L, McHugh
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2819. Remington G, Sloman L, Konsta
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2849. Ringdahl JE, Kitsukawa K, And
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2877. Rogers SJ. Interventions that
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2908. Rossignol DA. Novel and emerg
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2939. Rutter M, Kreppner J, Croft C
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2967. Sandt D. Social Stories for S
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2994. Scanlon K. Art therapy with a
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3023. Schneider CK, Melmed RD, Bars
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3054. Schwartz IS, Sandall SR, Garf
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3085. Shafer MS, Egel AL and Neef N
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3115. Shipley-Benamou R, Lutzker JR
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3143. Siller M and Sigman M. The be
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3173. Smith C, Felce D, Jones E, et
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3202. Snyder A, Bossomaier T and Mi
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3230. Spero MH. The emancipation of
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3259. Stephens CE. Spontaneous imit
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3289. Strambi M, Longini M, Hayek J
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3318. Suzumura K. How an autistic b
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3346. Tager-Flusberg H and Calkins
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3376. Taylor I, O’Reilly M and La
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3407. Thunberg G, Ahlsen E and Sand
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3435. Trembath D, Balandin S, Toghe
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3464. Turner-Brown LM, Perry TD, Di
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3492. Van Der Putt R, Dineen C, Jan
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3522. Vitiello B. Recent NIMH clini
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3553. Walenski M, Mostofsky SH, Gid
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3581. Weber RC and Thorpe J. Teachi
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3610. Wheeler JJ, Baggett BA, Fox J
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3637. Williams B. Mental handicap n
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3669. Wimpory D, Chadwick P and Nas
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3698. Worth S and Reynolds S. The A
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3728. Young JM, Krantz PJ, McClanna
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3759. Zuddas A, Di Martino A, Mugli
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Appendix F. Approach to Categorizin
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APPENDIX G. Discussion of Recent Sy
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one a casein free regime. Diets wer
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outcome data as Type 6, defined as
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Yes—no disclosures to make G7 Bai
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Table G1. Characteristics of recent
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Random assignment Appropriate compa
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Study Group design Random assignmen
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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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