Online Resource 1
How effective are drug treatments for children with ADHD at improving on-task behaviour and academic achievement in the school classroom? A systematic review and meta-analysis.
Vibhore Prasad, Ellen Brogan, Caroline A. Mulvaney, Matthew J. Grainge, Wendy Stanton, Kapil Sayal
Division of Primary Care
University of Nottingham
University Park
Nottingham
NG7 2RD
E-mail:
V. Prasad - Division of Primary Care, University of Nottingham
E. Brogan - East Midlands Healthcare Workforce Deanery
C.A. Mulvaney - School of Nursing/Division of Primary Care, University of Nottingham
M. J. Grainge - Division of Epidemiology and Public Health, University of Nottingham
W. Stanton - Information Services, University of Nottingham
K. Sayal - Developmental Psychiatry, University of Nottingham
Online Resource 1: Summary of included studies
Ajibola 1995 / N=6
Age: 9 to 12 years
Sex: male
Setting: Elementary school classroom
(USA) / Score 15 or above on Conners’ Teacher Rating Scale (CTRS) /
- Placebo + non-contingent reinforcer
- Low dose (0.3mg/kg) methylphenidate + non-contingent reinforcer
- High dose (0.7mg/kg) MPH + non-contingent reinforcer
- Low dose (0.3mg/kg) MPH + self reinforcement
- High dose (0.7mg/kg) MPH + self reinforcement
- Placebo + self-reinforcement.
5 day baseline
6 x 10 day treatment phases
1 for each treatment / 1.Amount of academic performance = comprehension questions answered in 30 mins
2.Accuracy of academic performance = number of questions correct/ total number of questions answered / 83% / No
Ballinger 1984 / N = 9
Age: 9-15 Sex: male only
years (mean 11.71)
Setting: classroom (type not specified)
(USA) / Not specified /
- Placebo
- Low dose MPH (0.3mg/kg)
- High dose MPH (0.6mg/kg)
- Durrell Analysis of Reading Difficulty
- Correct word recognition rate
- Correct comprehension rate
- Number of words per minute
Balthazor 1991 / N = 19
Age: 5.5-10.11 years, mean age 7.7 years
Sex: male
Setting: STP,
(USA) / DSM-III /
- Methylphenidate 0.3mg/kg
- Placebo
2.Reading comprehension – workbook with multiple choice questions, data averaged over 5 to 8 days per drug condition. % attempted and % correct in timed 10 min blocks. Completed 1 to 2 hours after medication ingestion. / 100% (Four young children were non-readers) / No
Barkley 1991 / N = 40
Age: 6-11 years
Sex: 36 male, 4 female
Setting: school classroom /clinic,
(USA) / Score above 93rd percentile on Child Attention Problems rating scale. /
- Placebo
- Low dose (L) 5mg methylphenidate bid
- Moderate dose (M) 10mg methylphenidate bid
- High dose (H) 15mg methylphenidate bid
- Off tasks
- Fidgets
- Out of seat
- Vocalises
- Plays with objects
- (Every 30 seconds as seen on videotape)
AND - Number of problems completed
- % of problems correct
Biederman 2007 / N = 52
Age: 6-12 years, mean 9.1 years
Sex: 33M, 19F
Setting: analogue classroom, 4 sites, school laboratory environment , (USA) / DSM-IV TR /
- Placebo (1 week)
- MAS XR (active control, mixed amphetamine salts extended release, 1 week)
- LDX (lisdexamfetamine disemylate, which is converted to dexamphetamine following ingestion)
2.PERMP = secondary measure (Permanent Product Measure of Performance)
- PERMP – A = attempted
- PERMP – C = correct
4.SKAMP attention rating (independent observer) / 96% / No
Brams 2008 / N = 86
Age: 6-12 years, mean 9.5 years
Sex: 53M, 33F
Setting: laboratory classroom (USA) / DSM-IV /
- Dexmethylphenidate ER 20mg/day
- Placebo
2.PERMP – 10 minute pencil and paper maths test
- Attempted
- Correct
Brown RT 2006 / N = 153
Age: 8-12, mean 9.9 years (S.D. 1.3)
Sex: 80.4% M
Setting: classroom; 10 investigational sites,
(USA) / DSM-IV /
- Atomoxetine, mean dose 32mg/kg (S.D. 0.30) with a range of 0.8mg/kg-1.8mg/kg
- Placebo
Carlson 1992 / N = 24
Age: 6 - 12 years
Sex: Male
Setting: Academic classroom, 8 week STP,
(USA) / DSM-III-R /
- Placebo
- Methylphenidate 0.3mg/kg (low dose)
- Methylphenidate 0.6mg/kg (high dose)
2. Timed arithmetic task:
- Number attempted
- % correct
- Number attempted
- % correct
5.Children’s self rating questionnaire for classroom behaviour and academic performance, 8 questions rated 1-10. / NR / Yes
Chacko 2005 / N = 36
Age: 5-6 years
Sex: 32M, 4F
Setting: STP
(USA) / DSMIII-R or DSM-IV /
- Placebo
- Methylphenidate 0.3mg/kg
- Methylphenidate 0.6mg/kg
2. Productivity (% seatwork completed)
3.Accuracy (% seatwork correct) / NR / Yes
Dopfner 2004 / N = 82
Age: 8-14 years, mean = 10.00 years, (SD 1.6)
Sex: 71M, 8F
Setting: analogue classrooms, 7 centres, (Germany) / ICD-10 or DSM-IV /
- Once daily extended release methylphenidate
- Twice daily immediate release methylphenidate
- Placebo
2. PERMP 15 minute, age appropriate math test
- Number attempted
- % correct
Douglas 1986 / N = 16
Age: 7.0-11.6 years, mean 9.2, SD 1.65
Sex: 15M, 1F
Setting: laboratory/regular school classroom, (Canada) / DSM-III /
- Placebo
- Methylphenidate 0.3 mg/kg
- number attempted
- number completed correctly
- accuracy score based on % correct out of number attempted
- efficiency: number completed per minute spent
- number correct
- accuracy score (items correctly corrected out of those identified as wrong)
- time spent
- effort
- number correct
- time spent studying
- effort
DuPaul 1993 / N = 56
Age: 6-11 years,
Sex: 46M, 10F
Setting: regular elementary school classroom (USA) / DSM-III /
- MPH 5mg
- MPH 10mg
- MPH 15mg
- MPH 20mg
- Placebo
- % of observations on-task.
Elia 1992 / N = 33
Age: mean 111.2 months, SD 16.51
Sex: Male
Setting: out-patient unit school, special education classroom
(USA) / DSM-III or 2 standard deviations above normal on CTRS /
- Placebo
- Methylphenidate (max daily dose 90mg)
- Dextroamphetamine (max daily dose 45mg)
- Number attempted
- % correct
- Subtest scores for reading (number attempted and % correct)
- Number attempted
- % correct
- Subtest scores for arithmetic (number attempted and % correct):
- Addition
- Subtraction
- Addition and subtraction
- Addition with carrying
- Subtraction with borrowing
- Addition and subtraction with carrying or borrowing
- Multiplication
- Division
Evans 1991 / N = 9
(9 in analysis, initially recruited 21)
Age: 11.6-15.0 years
Sex: Male
Setting: Lecture classroom, STP,
(USA) / DSM-IIIR / 1.Placebo
2.Low dose MPH (0.3mg/kg or 0.15mg/kg in overweight)
3. 3. High dose MPH (0.6mg/kg or 0.3mg/kg in overweight)
/ 6 weeks / 1.Daily quiz score % answered correctly
2. Lecture Q/A assignment % answered correctly
3.Lecture summary assignment % of main ideas produced
4.Cumulative test % correct
5.Classroom observations of conflict and attention deficit disorders (COCAAD) % of intervals with on-task behaviour / 43% / Yes
Evans 2001 / N = 45
Age: mean = 13.8, SD =1.2
Sex: 40M, 5F
Setting: Junior High School class in STP, (USA) / DSM-III-R / 1.Placebo
2.10mg MPH twice and 5mg MPH once
3.20mg MPH twice and 10mg MPH once
4.30mg MPH twice and 15mg MPH once / 8 weeks, 2 unmedicated, 6 medicated crossover / 1.History worksheet: % correct
2. History quiz: % correct
3.Notes :
- % main ideas recorded
- % details recorded
- Words written
- Sequence length
- Idea (rated 1 poor – 5 superior)
6.Homework completed: % of days in drug condition / NR / Yes
Fabiano 2007 / Age: 5-12 years mean 9.35, SD 1.98
Sex: 44M, 4F
N = 48
Setting: analogue classroom setting, USA / DSM-IV /
- Placebo
- MPH 0.15mg/kg
- MPH 0.30mg/kg
- MPH 0.60mg/kg
Gorman 2006 / N = 77
Age: 6-12 years
Sex: 56M, 19F (2 unspecified)
Setting: regular school classroom
(US) / DSM-IV /
- Placebo
- Methylphenidate dose increased over 21 days from 0.25mg/kg to 0.4mg/kg plus half-dose afternoon dose
- Z score representing number correct, based on no-medication baseline
- Task incompatible behaviours (proportion of observed behaviours: off-task, fidgeting, vocalises, out of seat)
James 2001 / N = 35
Age: mean = 9.1 SD 1.5, range 6.9-12.2 years
Sex: 21M, 14F
Setting: research school
(US) / DSM-IV / 1.Placebo
2.Adderall
3.Immediate-release dextroamphetamine
4.Dextroamphetamine Spansules. / 8 weeks (plus 3 weeks unmedicated observation) / 1.5 minute timed math task (4 hours post medication), difficulty level selected for each child’s ability.
- Total responses
- Correct responses (both summed weekly)
Klein 1991 / N = 83
Age: 6-12 years, mean 8.55 (SD 2.02)
Sex: NR
Setting: NR / American Psychological Association (APA) 1968 criteria /
- Placebo (42 children)
- MPH (41 children)
- (Thioridazine*
- MPH + thioridazine)*
- Reading
- Arithmetic
- Spelling
- Gray Oral Reading Test
McCracken 2003 / N = 51
Setting: analog classroom, 4 academic sites, USA
Age: 6-12, mean 9.5, SD 1.9
Sex: 44M, 7F
(US) / DSM-IV /
- Placebo
- SLI381 10mg
- SLI381 20mg
- SLI381 30mg
- Adderall® - active control
- Attention
- Deportment
- Number attempted
- Number correct
McGough 2006 / N = 80
Age: 6-12 years mean 9.1, SD 1.7
Sex: 57M 22F (I LTF unspecified)
Setting: laboratory classroom sessions,
(USA) / DSM-IV-TR /
- Placebo Transdermal System (PTS)
- Methylphenidate Transdermal System (MTS)
- Deportment (primary measure)
- Attention
- Number attempted
- Number correct
Pelham 1985 / N = 29
Age: 5.5-11.5,
Setting: STP classroom (day) USA / DSM-III /
- Placebo
- Methylphenidate 0.15mg/kg
- Methylphenidate 0.30mg/kg
- Methylphenidate 0.60mg/kg
- Number attempted
- Number correct
- Number attempted
- Number correct
4.Classroom observations:
On-task behaviour, observed in 1st 15 mins of class proportion of intervals on-task, averagerecorded over the week. / 100% / No
Pelham 1987 / N = 13
Age: mean 8.8, (SD 1.50), range 6 years and 7 months to 11 years
Sex: male
Setting: STP (USA) / DSM-III /
- Placebo
- MPH (standard release)
- SR-20
2. 2 minute timed arithmetic drill
- Number attempted
- % completed correctly
- Number attempted
- % completed correctly
- Accuracy (% correct)
- Productivity (% completed)
Pelham 1989 / N = 24
Age: 5 years. 3
months – 11 years 3 months
Sex: 12 male 12 female
Setting: STP classroom / DSM-III /
- Placebo
- MPH 0.3mg/kg
- On-task behaviour
- Number attempted
- Percentage correct
- Number attempted
- Percentage correct.
- Productivity (amount completed)
- Accuracy (amount correct)
Pelham 1990 / N = 22
Age: 8.08 to 13.17 years; mean 10.39, SD 1.38
Sex: Male
Setting: STP, (USA) / DSM-III-R / 1.Placebo
2.10mg standard MPH
3. Comparable dose SR-20
4.56.25mg pemoline
5.10mg Dexedrine spansules (DS) / 6.5 weeks (medicated/ placebo) plus 1.5 weeks previous adaptation / 1.10 minute timed reading task
- Number attempted
- % correct
- % completed (productivity)
- % correct (accuracy)
Pelham 1993 / N = 31
Age: 5.42-9.92 years, mean 8.23
Sex: male
Setting: STP, (USA) / DSM-III-R /
- Placebo
- Low dose MPH (0.3mg/kg except in 4 obese = 0.15mg/kg)
- High dose MPH (0.6mg/kg except in 4 obese = 0.3mg/kg)
- % observed intervals on-task
- % completed (productivity)
- % correct (accuracy)
Pelham 1999 (April) / N = 27
Age: mean = 9.6, SD .6, range 5.8 to 12.7 years
Sex: 21M, 4F (2 unspecified)
Setting: 8 week, weekday STP,
(USA) / DSM-IV /
- Placebo
- Ritalin (MPH) 10mg
- Ritalin (MPH) 17.5mg
- Adderall 7.5mg
- Adderall 12.5mg twice daily
- Productivity (% complete)
- Accuracy (% correct)
- % observations on task
Pelham 1999 (Dec) / N = 21
Age: 6-12 years, mean 10.26 (SD 1.9)
Sex: 19M, 1F
Setting: STP, (USA) / DSM-IV /
- Placebo
- 0.3mg/kg MPH three times daily
- 0.3mg/kg MPH twice daily
- 0.3mg/kg MPH morning only
- 0.3mg/kg Adderall twice daily
- 0.3mg/kg Adderall morning plus 0.15mg/kg late afternoon
- 0.3mg/kg Adderall morning only
- Productivity (% complete)
- Accuracy (% correct)
Pelham Jr 2005 / N = 36
Age: 6-13, mean 9.6
Sex: 33M, 3F
Setting: STP at 3 sites,
(US A) / NIMH Diagnostic Interview Schedule for Children /
- Placebo (patch)
- MTS 6.25cm2 (0.45mg/h)
- MTS 12.5cm2 (0.9mg/h)
- MTS 25cm2 (1.8mg/h)
- % completion
- % correct (accuracy)
Rapport 1985 / N = 12
Age: 6-10 years
Sex: male
Setting: regular school classroom (and laboratory, but lab results not used in this extraction)
(USA) / DSM-III /
- Placebo
- 5mg MPH
- 10mg MPH
- 15mg MPH
2.Academic seatwork (arithmetic and language arts) recorded daily:
- % complete
- % accurate
Rapport 1986 / N = 14
Age: 6-10 years (mean 7.75 years)
Sex: 12 male, 2 female
Setting: Child’s regular classroom / DSM-III /
- Placebo
- MPH 5mg
- MPH 10mg
- MPH 15mg
- Behavioural observation – on-task or off-task
- Morning assignment (arithmetic &/or phonic)
- % completed
- % accurate
Rapport 1987 / N = 42
Age:6-11 years, mean 8.5 years.
Sex: M=37, and F=5
Setting: regular classroom / DSM-III /
- Placebo
- MPH 5mg fixed doseMPH10mg fixed dose
- MPH 15mg fixed dose
- MPH 20mg fixed dose
2.Seatwork
- Percentage completed
- Percentage accurate.
- AES (academic efficiency score)
Rapport 1994 / N = 104
Age: 6-11 years,
Sex: 86M, 15F (3 unspecified, drop outs)
Setting: regular classroom
(USA) / DSM-III /
- Placebo
- 2. 5mg MPH
- 10mg MPH
- 15mg MPH
- 20mg MPH
2. Assigned seatwork – consistent with child’s ability level (1.5-2 hours post-dose)
- % complete
- % accurate/correct
Richardson 1988 / N = 58
Age: 7-13
Sex: NR
Setting: regular classroom with some laboratory measures? Not explicitly described / DSM-III /
- Placebo
- 0.3mg/kg MPH
- 0.5mg/kg MPH
- 0.7mg/kg MPH
2.Peabody Individual Achievement Test (subsets including Reading Recognition, Comrehension and Math)
3.Achievement rate: estimated grade equivalent reading score (RGL) (averaging from above tests) / 72% / No
Silva 2005 / N = 54 (53 completed)
Age: 6-12 years, mean 9.4 years
Sex: 34M, 20F
Setting: Laboratory classroom
(USA) / DSM-IV /
- Placebo
- ER-MPH 20mg
- ER-MPH 40mg
- OROS-MPH 18mg
- OROS-MPH 36mg
- attention rating (primary measure)
- deportment rating (secondary measure)
- objective measure of academic productivity
- 400 problems, children instructed to work through as many as possible in 10 minutes.
- Math-Attempted score
- Math-Correct score
Silva 2006 / N = 54
Age: 6-12 years, mean 9.4, SD 1.6
Sex: 38M, 16F
Setting: laboratory classroom
(USA) / DSM-IV / 1.Placebo
2.d-MPH-ER 20mg per day / 12 days / 1.SKAMP (1 hour post-dose)
- Combined score
- Deportment
- Attention
- Number attempted
- Number correct
Swanson 1998 / N = 33
Age: 7-14 years, mean 10.58, SD 1.81
Sex: 26M, 7F
Setting: laboratory classroom
(USA) / DSM-IV /
- Placebo
- Active control (MPH, average dose 12.5mg)
- Adderall® 5mg
- Adderall® 10mg
- Adderall® 15mg
- Adderall® 20mg
- Attention
- Deportment
- Number attempted
- Number correct
Swanson 2004 / N=184[†]
Age: 6-12 years, mean 9.6
Sex: 135M, 48F
Setting: Laboratory classroom
(USA) / DSM-IV /
- Placebo
- Concerta (MPH extended release)
- Metadate (MPH extended release)
- SKAMP
- 6 Deportment items (interacting with other children, interacting with adults, remaining quiet, staying seated, complying with the teacher’s directions, and following the classroom rules)
- 7 attention items (getting started, sticking with tasks, attending to an activity, making activity transitions, completing assigned tasks, performing work accurately, and being neat and careful while writing or drawing)
- PERMP
- PERMP – A = attempted
- PERMP – C = correct
Tannock 1989 / N = 12
Age: 6-11 years, mean 8.4 (SD 1.4)
Sex: 10M, 2F
Setting: laboratory classroom, (Canada) / DSM-III /
- Placebo
- Low dose MPH (0.3mg/kg)
- High dose MPH (1.0mg/kg)
- Total correct
- Total errors
- Total correct
- Total errors
Vyse 1989 / N = 26
Age: 6-12 years, mean 8.5 years, SD 1.4
Sex: 24M, 2F
Setting: Children’s Learning Clinic/regular school classroom
(USA) / DSM-III /
- Placebo
- 5mg MPH
- 10mg MPH
- 15mg MPH
- 20mg MPH
- On-task behaviour (% intervals on-task)
- Regularly assigned academic work (arithmetic problems or language arts, 1.5-2 hours post-dose)
- % complete
- % correct
- AES (% completed correctly)
Wietecha et al. 2009 / N = 178 (267 in acute phase, 178 in maintenance phase)
Age: 13-16 years, mean 14.45
Sex: 111 male, 67 female
Setting: laboratory classroom
(USA) / DSM-IV-TR / Acute phase:
Number of groups = 2
- Fast titration – 0.5mg/kg/day for 3 days, 1.2mg/kg/day for remainder,
- Slow titration 0.5mg/kg/day for 7-9 days, then 1.0mg/kg/day for 7-9 days, then 1.2mg/kg/day for remainder
Number of groups = 2
- Low-dose 0.8mg/kg/day
- High-dose 1.4mg/kg/day (not exceeding 100mg/day regardless of pt weight).
2. Grade point average (in English, Math, Science & Social Studies) / 56/178
31% / No
Wigal 2009 / N = 129
Age: 6-12 years, mean age 10.1 (SD 1.5) years.
Sex: 98 males, 31 female
Setting: laboratory school, multicenter
(USA) / DSM-IV-TR /
- Placebo
- Lisdexamfetamine dimesylate
- SKAMP deportment rating (SKAMP-D)
- SKAMP attention rating (SKAMP-A)
- SKAMP-quality of work
- PERMP – A = attempted
- PERMP – C = correct
Worrall 1993 / N = 63
Age: 5 years 8 month 10 years
Sex: 52 male, 11 female
Setting: not described.
(South Africa) / DSM-III / 1.Placebo (lactose)
2.MPH / 10 days /
- Language task
- % attempted
- % correct
- Effort deployed on task (1 = no effort to 7 = excellent effort)
- Maths task
- % attempted
- % correct
- Effort deployed on task (1 = no effort to 7 = excellent effort)
NR: Not reported
STP: Summer Treatment Programme