Table 2.

Clinical Trials Evaluating Effects of Stimulants on Academic Outcomes in Children with Coexisting ADHD and Reading Disorder

Source and Study Design	Sample Size of Children with ADHD+LD and Characteristics	Duration and Dose of Medication Treatment	Efficacy Measures	Findings	Comments	Oxford Quality Rating
Bental B et al (2008) Controlled clinical trialb with DBPC crossover methodology	-N=25 had ADHD+RD -7-11 years old -100% male, race not specified -RD criteria: <25th percentile in both NDB single word decoding and text reading subtests, or <15th percentile on either one	-Trial with single MPH dose -MPH dose was 0.3-0.4 mg/kg	-Word and non-word decoding accuracy (NDB) -Spelling (NDB) -Phonemic synthesis and deletion (NDB)	-MPH improved word and non-word decoding accuracy but not spelling accuracy, phonemic synthesis, or phonemic deletion.	-No correction for multiple comparisons	1b-
Dykman RA et al (1991) Cohort analytica	-N=82 had ADHD+RD -7-11 years old -Analyzed sample was 100% male and Caucasian -RD criteria: IQ≥90 AND WRAT reading and spelling subtest SS <90	-4 week trial -Treatment with low MPH dose (0.3mg/kg BID) and high MPH dose (0.6mg/kg BID)	-20-minute arithmetic task with addition and subtraction problems	-MPH improved arithmetic performance.	-Data on MPH effects analyzed for only 78% (N=64) of the ADHD+RD group	2b
Hechtman L et al (2005) Randomized controlled trial	-N=82 had ADHD+RD at study baseline (N=576 for whole sample) -7-9 years old -Whole sample: 80% male, 61% Caucasian -RD criteria: discrepancy between IQ and WIAT reading SS at the 5% significance level	-14 month trial -Children randomized to get rigorously titrated MPH (mean=38 mg/kg/day), combined MPH (mean=31 mg/kg/day), + behavior parent training, behavior parent training only, or usual community care (67% got ADHD medications: among those on MPH, mean=23 mg/kg/day)	-Meeting criteria for reading disorder (discrepancy between ability and reading achievement at the 5% significance level, as measured by the WISC-III and WIAT)	-Among those with LD at baseline, there was a borderline significant decrease in likelihood of meeting criteria for LD at the end of the trial in: 1) the MPH group compared to the community care group, 2) in the combined (MPH + behavior parent training) group compared to the community care group, 3) the behavioral parent training group compared to the community care group.	-Data was from the Multimodal Treatment Study of Children with ADHD (landmark trial of MPH efficacy in pediatric ADHD)	1b
Keulers EH et al (2007) Cohort analytica	-N=24 had ADHD+RD (N=9 had ADHD-only) -7-13 years old -71% male, race not specified -RD criteria: met DSM-IV criteria for RD and not improving in reading skills despite adequate remedial instruction for at least 6 months	-Study duration varied between 0.3 to 1.4 years -Mean MPH dose was 0.48 mg/kg/day	-Word reading/decoding (EMT and DMT) -Non-word decoding (Klepel Test)	-MPH produced larger improvements in word decoding and non-word decoding skills in the ADHD+RD than the ADHD-only group.	-Duration between pre- and post-assessments varied from 0.3 to 1.4 years -Limited description of inclusion criteria and MPH dosing protocol	2b
Tamm L et al (2017) Controlled clinical trialb	-N=78 had ADHD+RD -Grades 2-5 -68% male and 71% African American -RD criteria: IQ≥70 AND SS <90 on WJIII Letter Word Identification subtest, Word Attack subtest, or Basic Reading Skills composite.	-16 week trial -Ultimate/final medications prescribed were MPH for 46%, AMPH and/or DEX for 42%, ATX for 4%, and guanfacine for 6% (mean doses not reported)	-Word Reading and Pseudoword Decoding (WIAT-3)	-Word reading and pseudoword decoding skills improved more with a reading intervention than with medication treatment.	-Families also attended an average of 4.8 behavior training sessions in addition to child receiving ADHD medication	1b-
Tannock R et al (2018) Controlled clinical trialb with DBPC methodology	-N=65 had ADHD+RD -Ages 7-11 years old -75% male and 90% Caucasian -RD criteria: IQ>80 AND SS on ≥2 reading subtests [WRAT-3 Reading, WRMT-R Word Identification, WRMT-R Word Attack] at least 1.5 SD below age level or SS on all 3 reading subtests at least 1 SD below age level	-4 month trial -Maximum MPH dose was 0.7mg/kg BID or 20mg BID (whichever achieved first), mean dose not specified	-Speech-sound discrimination (GFW Sound Analysis subtest) -Word attack and word identification (WRMT-R) -Word decoding (KT and TOT -Passage comprehension (WRMT-R) -Arithmetic (WRMT-R)	-MPH improved speech-sound discrimination and arithmetic performance, but not word attack, word identification, decoding, or passage comprehension.	-Children with a history of poor response to stimulant medications excluded	2bc
Williamson D et al (2014) Controlled clinical trialb with DBPC crossover methodology	-N=46 had ADHD+LD (N=31 had RD, N=9 had MD, N=6 had RD+MD) -9-12 years old -69% male and 40% minority (African American or Hispanic) -RD criteria: scores 1-2 SD below the mean on the CTOPP Elision subtest and the GORT-4 fluency subtest -MD criteria: scores 1-2 SD below the mean on the WIAT-II-A Numerical Operations subtest	-6 week trial -MPH was titrated upward until clinician rated children as “much” or “very much” improved: best dose was 18mg for 13%, 36mg for 26%, and 54mg for 61% of ADHD+LD group	-Handwriting (THS-R) -Math computation (PERMP) -Reading Fluency (DIBELS) -Reading Comprehension (GSRT)	-MPH improved reading fluency, handwriting, and math computation skills, and had borderline significant beneficial effects on reading comprehension.	-No correction for multiple comparisons -Children with a history of stimulant non-response excluded	2bc

^aNaturalistic, open label study, with pre- and post-measures

^bDescribed as randomized by authors but classified as a controlled clinical trial rather than a randomized control trial due to lack of detail regarding randomization procedures

^cQuality rating downgraded from 1b due to exclusion of children with history of poor response to stimulants

ADHD=attention-deficit/hyperactivity disorder

AMPH=Amphetamine

ATX=Atomoxetine

DBPC=Double-blind placebo-controlled

DEX=Dextroamphetamine

DIBELS=Dynamic Indicators of Basic Early Literacy Skills

DMT=Three Minutes Test

DSM-IV=Diagnostic and Statistical Manual for Mental Disorders-4^th edition

EMT=One Minute Test

GFW=Goldman-Fristoe-Woodcock

GORT-4=Gray Oral Reading Test-4^th edition

GSRT – Gray Silent Reading Test

KT=Keyword Test

LD=Learning Disorder

MD=Math Disorder

MPH=Methylphenidate

NDB=Nitzan Diagnostic Battery for Reading Performance in Hebrew

PB=Placebo

PERMP – Permanent Product Math Test

RD=Reading disorder

SS=Standard score

THRS-R=Test of Handwriting Skills-Revised

TOT=Test of Transfer

WIAT=Wechsler Individual Achievement Test

WISC=Weschler Intelligence Scale for Children

WJIII=Woodcock Johnson III Tests of Achievement

WRAT=Wide Range Achievement Test

WRMT-R=Woodcock Reading Mastery Tests-Revised