Psychopharm Paper

R E V I E W

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 Mulvaney •

Matthew Grainge • Wendy Stanton • Kapil Sayal

Received: 25 March 2012 / Accepted: 7 November 2012 / Published online: 21 November 2012

� Springer-Verlag Berlin Heidelberg 2012

Abstract Attention-deficit hyperactivity disorder (ADHD)

has a significant impact on children’s classroom behaviour,

daily functioning and experience of school life. However,

the effects of drug treatment for ADHD on learning and

academic achievement are not fully understood. This

review was undertaken to describe the effects of methyl-

phenidate, dexamfetamine, mixed amfetamine salts and

atomoxetine on children’s on-task behaviour and their

academic performance, and to perform a meta-analysis to

quantify these effects. Nine electronic databases were

systematically searched for randomized controlled trials

comparing drug treatment for ADHD against (i) no drug

treatment, (ii) baseline (in crossover trials), or (iii) placebo;

reporting outcomes encompassing measures of educational

achievement within the classroom environment. Forty-

three studies involving a pooled total of 2,110 participants

were identified for inclusion. Drug treatment benefited

children in the amount of school work that they completed,

by up to 15 %, and less consistently improved children’s

accuracy in specific types of academic assignments, such as

arithmetic. Similar improvements were seen in classroom

behaviour, with up to 14 % more of children’s time spent

‘‘on task’’. Methylphenidate, dexamfetamine and mixed

amfetamine formulations all showed beneficial effects on

children’s on-task behaviour and academic work comple-

tion. Atomoxetine was examined in two studies, and was

found to have no significant effect. These review findings

suggest that medication for ADHD has the potential to

improve children’s learning and academic achievement.

Keywords ADHD � Attention-deficit hyperactivity disorder � Medication � Education � Achievement

Introduction

Attention-deficit hyperactivity disorder (ADHD) affects an

estimated 5 % of schoolchildren worldwide, and typically

presents in early childhood [1–3]. Symptoms characteristic

of ADHD include hyperactivity, impulsivity and inatten-

tion, which are more pronounced than might be expected

for a child’s developmental age [4]. The impairments at

school and in academic achievement caused by these

symptoms are some of the most profound and common

difficulties faced by children and adolescents with ADHD

[5]. Studies by Fergusson et al. [6] have suggested an

association between attentional difficulties and these aca-

demic impairments. Such impairments have been shown to

affect a child’s quality of life in the short [7, 8] and long

[8–10] term. Studies show that children with ADHD have a

lower IQ in comparison to peers [11, 12] and a study by

Duric and Elgen [13] found that one-third of clinically

referred children with ADHD had low IQ, although the

effect of ADHD on IQ appears less prominent in adults

with ADHD and in non-clinical samples [14]. Children

with ADHD also have lower academic attainment after

adjusting for IQ [15–17]. These children are likely to

underachieve at school, complete less work and reach

lower grades [16]; a review by Polderman et al. [18]

demonstrated that children with attention problems are at

risk for lower academic achievement and subsequent

adverse outcomes later in life.

Electronic supplementary material The online version of this article (doi:10.1007/s00787-012-0346-x) contains supplementary material, which is available to authorized users.

V. Prasad (&) � E. Brogan � C. Mulvaney � M. Grainge � W. Stanton � K. Sayal University of Nottingham, Nottingham, Nottinghamshire, UK

e-mail: [email protected]

123

Eur Child Adolesc Psychiatry (2013) 22:203–216

DOI 10.1007/s00787-012-0346-x

Studies to date have utilized a range of settings and

measures to assess the impact of treatment for ADHD

children’s classroom behaviour and academic performance.

The measure of on-task behaviour (the length of time

during observed intervals that children spend paying

attention to their task) has been widely used in studies. A

variety of studies have similarly examined out-of-seat

behaviour (the amount of observed intervals that children

spend away from their assigned seat or work area), as well

as other behavioural measures and measures of attention.

Measures of academic performance are more variable,

with many authors utilizing measures of ‘seatwork com-

pletion/productivity’: the percentage of a child’s assigned

seatwork that they completed, and ‘seatwork accuracy’: the

percentage of a child’s assigned seatwork that they

answered correctly), others using academic results from

tasks such as arithmetic and reading tests.

Common settings for such studies include children’s

regular classrooms, or alternatively the Laboratory School

Protocol classroom [19]: a controlled environment

designed for the evaluation of medications, in which it is

possible to examine dosing, safety, attention, behaviour

and classroom productivity by the administration of

activities tailored to children’s age and development, as

well as other simulated classrooms.

Drug treatment is typically used for severe ADHD and

for ADHD refractory to behavioural and psychological

interventions [20]. Several literature reviews have evalu-

ated the effects of drugs on academic outcomes for children

with ADHD. Swanson [21] concluded that stimulants

improve attention, concentration and motivation, but found

no clear effect on academic performance. Similarly, a

review by Jadad et al. [22] determining the effectiveness

and safety of pharmacological interventions concluded that

drug interventions did not result in improved academic

performance. Schachar et al. [23] undertook a systematic

review on the long-term treatment of ADHD and from 14

Randomized controlled trials (RCTs) in which treatment

was administered for 12 weeks or more. They concluded

that there was little evidence for improved academic per-

formance with stimulants. However, Backman and Fire-

stone’s literature review [24] suggested that stimulant

medication is more effective than behaviour therapy in

improving classroom behaviours and attentional processes

in hyperactive children. Carlson and Kruer [25] reviewed

the level of support for prescription stimulants (methyl-

phenidate-based), a prescription non-stimulant (atomoxe-

tine) and a readily available/consumed stimulant (caffeine).

They found strong empirical support for methylphenidate-

based medications, and emerging support for atomoxetine,

but a lack of evidence for beneficial effects of caffeine, and

stressed the need for further examination of the effects of

pharmacological approaches to ADHD treatment within

school settings to better understand the benefits for chil-

dren’s academic, social and behavioural challenges.

Recent empirical studies have shown medication-related

improvements in the school domain, including academic

productivity, reading and mathematics scores and working

memory [26, 27]. Hale et al. [28] suggested that cognitive

function and academic achievement can be improved by

an optimized medication dose, and a study by Semrud-

Clikeman et al. [29] demonstrated that children who had a

history of medication use for ADHD displayed better

executive and academic function than children who were

treatment naı̈ve, even if they subsequently stopped medica-

tion. Chronic academic and educational underachievement

due to ADHD have been demonstrated to have long-term

implications for children’s future health, socioeconomic

and employment outcomes and occupational functioning

[7–10, 30–33].

Thus, the effect of drugs on academic outcomes for

children with ADHD, whilst of high importance, remains

unclear, and there is a lack of systematic data in this area.

Hence, this systematic review was undertaken to identify

studies describing the effects of four common drug treat-

ments for ADHD—namely, methylphenidate, dexamfeta-

mine, mixed amfetamine salts and atomoxetine—on

out-of-seat and on-task behaviour, and academic achieve-

ment; a meta-analysis was performed to quantitatively

determine the effect of these drug treatments on on-task

behaviour, school grades and related measures of academic

performance.

Methods

An electronic search was undertaken of the following

databases from the earliest of 1980 or the date of inception

to June 2010: (1) MEDLINE, (2) EMBASE, (3) PsycINFO,

(4) CINAHL, (5) Web of Knowledge, (6) Education

Resources Information Center (ERIC), (7) British Educa-

tion Index (BEI), (8) Australian Education Index (AEI) and

(9) CAB Abstracts. Databases were searched using the

following search string ‘‘ADHD AND drug treatment AND

(Educational achievement or social behaviour) AND edu-

cational/school environment’’ as shown in Table 1. Lists of

references from publications identified as being relevant to

the review were examined. Grey literature and potentially

relevant unpublished literature were searched via CAB

Abstracts. No language restrictions were used.

Studies were then selected for inclusion based upon

criteria outlined in Table 2.

Studies using clinician or teacher rating scales were

included if the rating focussed specifically on on-task

behaviour, or out-of-seat behaviour, in a classroom or

analogue classroom setting, or on academic achievement in

204 Eur Child Adolesc Psychiatry (2013) 22:203–216

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these settings. Ratings of broader ADHD symptoms and

parental ratings were excluded.

Titles and abstracts were independently reviewed by two

authors (EB and CM) according to the inclusion criteria.

Where there was disagreement, this was resolved by dis-

cussion with a third reviewer (VP). The full text of retained

papers was then independently reviewed by two authors

(EB and CM), with any disagreements again resolved by

discussion with the third reviewer (VP). Data extraction

was performed by EB using a data collection form, which

included risk of bias assessment. A second reviewer (CM)

reviewed all data collection forms.

For studies that used a within-subject crossover design, the

mean and standard error of the participant-specific differences

between experimental and control measurements was calcu-

lated [34]. Where this was stated, standard errors for the mean

difference were calculated or imputed using the correlation

coefficient if either the t-statistic (or F-statistic), p value, or

95 % confidence interval from the paired analysis was avail-

able, as outlined in the Cochrane Handbook section 16.4.6

[34]. Data were entered into Review Manager (The Cochrane

Collaboration) [35]. Where data were incomplete, authors

were contacted by email. If data remained incomplete, find-

ings were summarized descriptively.

Meta analyses were performed where complete data

were presented for the comparison in two or more studies.

For each intervention seatwork productivity, seatwork

accuracy and the percentage of intervals during classroom

observation in which the participants displayed on-task

behaviour were analysed. A random-effects model was

used for all analyses to allow for heterogeneity. As all

outcomes included in the meta-analyses produced contin-

uous data (mean percentages) the results from the meta-

analyses are expressed as pooled mean differences (MDs)

with a 95 % confidence interval. Heterogeneity across

studies was measured using the Chi-squared test, and

Table 1 Search strategy to identify studies for inclusion

Searches:

1. Attention Deficit Disorder with Hyperactivity OR ADHD OR Attention-deficit hyperactivity disorder OR Attention deficit hyperactivity

disorder OR attention deficit disorder OR Attention Deficit and Disruptive Behaviour Disorders OR hyperactive OR ADDH

2. Drug treatment OR drug therapy OR drug OR pharmacological OR stimulant OR Central Nervous System Stimulants OR medication OR

methylphenidate OR Ritalin OR atomoxetine OR dexamfetamine OR Dextroamphetamine OR dexamphetamine OR concerta XL OR

equasym XL OR medikinet OR Strattera

3. Learning disorders OR learning OR ability OR aptitude OR achievement OR educational OR academic achievement OR attainment OR

exam results OR examination results OR work OR schoolwork OR classwork OR academic work OR performance OR literacy OR

numeracy

4. Education OR special education OR school OR class OR teaching OR mathematics OR GCSE OR reading OR SATS OR academic

5. Children OR child OR p?ediatric

6. 1 AND 2 AND 3 AND 4 AND 5

7. Limit 6 to humans

? is a wildcard character

Table 2 Criteria used to select studies for inclusion

Criteria:

1. Study subject is ADHD as core condition (including all ADHD subtypes). Studies that primarily focused on the co-morbidity between

ADHD and other conditions (e.g. autistic spectrum disorders, learning disability, conduct disorder, oppositional defiant disorder) were

excluded

2. Intervention is drug treatment for ADHD compared with no drug treatment OR baseline OR placebo; drug treatment to include

Methylphenidate, Dexamfetamine, Mixed Amfetamine Salts, Atomoxetine, Ritalin, Concerta XL �

, Equasym �

, Medikinet �

, Strattera �

and

Adderall �

3. Outcomes are qualitative and quantitative measures of educational achievement and learning ability within a classroom or school

environment (to include analogue classroom settings or summer-school programs with a classroom setting); measures to include school

grades, classroom observations of on-task and out-of seat behaviour, measures of academic performance such as test results for maths or

language arts, and participant ratings of their own academic performance in the classroom

4. Children and young people aged 4–16 years (UK school age)

5. Human participants only

6. Randomized controlled trials (RCTs) only

Eur Child Adolesc Psychiatry (2013) 22:203–216 205

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quantified using I2 values. Substantial heterogeneity was

defined as I 2 [50 %.

Study selection and characteristics

Forty-three studies were identified for inclusion in this

review (Fig. 1). Thirty-nine studies were from the US, one

from Europe, one from South Africa and two from Canada.

Online Resource 1 presents a summary of included studies.

Forty-one papers used a within-subject crossover design

[36–76]; two papers used a between-subjects design [77,

78]. In all studies utilizing a crossover design, children

were randomized to order of intervention, with an average

of 2 weeks per intervention.

The review included a pooled total of 2,110 participants.

The majority of studies involved participants aged

5–12 years. More males were included than females; ten

studies included only males [41, 42, 45, 50, 51, 58–60, 62,

70]. Outcomes were measured in a variety of classroom

settings: fifteen studies were set in a conventional academic

classroom [41, 43, 45, 48, 49, 54, 62, 63, 66, 70, 73–77],

fifteen in analogue or laboratory classrooms [36, 37, 40, 44,

47, 53, 55, 56, 64, 65, 67–69, 71, 78] and twelve in

classrooms that were part of Summer Treatment Programs

[38, 39, 42, 46, 51, 52, 57–61, 72].

Sixteen studies assessed the percentage of observed on-

task behaviour [38, 39, 45, 49, 51, 52, 57, 58, 60, 62, 63, 65,

66, 72–74]. Fifteen studies reported the percentage of

assigned seatwork completed by their participants [36, 38,

39, 45, 46, 53, 57–63, 72, 74]; fourteen of these also

reported the percentage of assigned seatwork answered

correctly [36, 38, 39, 45, 46, 57–63, 72, 74]. Four studies

presented the participants’ Academic Efficiency Score (a

score combining seatwork completion and seatwork correct

to represent the percentage of academic assignments com-

pleted correctly) [49, 63, 66, 74]. Twenty-three studies

reported academic performance using an arithmetic test [36,

37, 40, 43–45, 47, 48, 50, 54–58, 64, 65, 67–69, 71, 72, 76,

77]; of these nine used the externally validated Permanent

Product Measure of Performance (PERMP) test [36, 37, 40,

44, 47, 56, 64, 67, 69] (a 10 min arithmetic test with out-

comes on number of problems attempted and number cor-

rect) [36] and eleven used independently developed and

unvalidated arithmetic tests [45, 48, 50, 55, 57, 58, 65, 68,

71, 72, 76]. Twelve studies assessed academic performance

using reading comprehension tests [41, 42, 45, 50, 57–59,

70–72, 75, 76] and three studies assessed spelling [48, 57,

71]. Eleven studies examined other learning-related out-

comes such as counting [42], the Academic Performance

Rating Scale (APRS) [77], arithmetic self-correction [48],

quiz scores, grade-point average (for English, maths, sci-

ence and social studies) [78], the Woodcock-Johnson III

tests of achievement [78], homework completed [51, 52],

morning assignment percentage completed and percentage

accurate [73], the Peabody Individual Achievement Test

[75] and task-incompatible behaviours such as fidgeting and

vocalizing [54] and the SKAMP scale. The Swanson,

Kotkin, Agler, M-Flynn and Pelham Scale (SKAMP) [79] is

a ten item measure assessing ADHD-related behaviours in

the classroom context, recorded by an independent obser-

ver, that impact school success [80], encompassing on-task

and out-of-seat behaviours, as well as initiation of work,

peer and staff interactions, quietness, work completion and

accuracy, attention and transitions.

The majority of studies (thirty-seven) assessed the

effects of methylphenidate (MPH) [38–54, 56–66, 68–76],

and all of these compared methylphenidate to placebo.

Thirty-two studies assessed standard-release methylpheni-

date [38–54, 57–60, 62, 63, 65, 66, 70–76] and six exam-

ined extended-release preparations [40, 47, 58, 64, 68, 69].

Two studies examined the effects of transdermal methyl-

phenidate patches [56, 61]. Of the studies that examined

the effects of methylphenidate, six solely measured the

effects of low-dose methylphenidate (average 0.3 mg/kg)

[38, 42, 48, 54, 72, 76] and two solely the effects of high-

dose methylphenidate [44, 64]. Twenty-three studies

assessed two or more different doses of methylphenidate

[38, 41, 43, 45, 46, 49, 51–53, 57, 60–63, 65, 66, 68–71,

73–75]. Six studies assessed the effects of mixed amfeta-

mine formulations (mixed amfetamine salts, ‘‘MAS’’ or

‘‘Adderall �

’’) [36–40, 55]; of these, four examined stan-

dard-release preparations [38–40, 55], one examined an

extended-release preparation [36] and one examined both

[37]. Five studies examined the effects of dexamfetamine

[36, 50, 55, 59, 67]; of these, one examined a standard-

release preparation [50], three assessed extended-release

preparations [36, 59, 67], and one assessed both standard

and extended-release preparations [55]. Only two studies

examined the effects of atomoxetine [77, 78].

Twenty-nine studies were not suitable for inclusion in

the meta-analysis because data were not sufficient, or an

insufficient number of studies used the same outcome

measure [36, 37, 40–43, 48, 50, 54–57, 62–64, 66–78].

Results

Effects on on-task behaviour and seatwork productivity

Methylphenidate

Eighteen studies assessed the effects of methylphenidate on

on-task behaviour [37–39, 45, 49, 51, 52, 57, 58, 60, 62, 63,

65, 66, 68, 72–74] and all but one [72] found that meth-

ylphenidate significantly increased on-task behaviour. A

pooled analysis of low-dose methylphenidate versus

206 Eur Child Adolesc Psychiatry (2013) 22:203–216

123

Fig. 1 A flow diagram to illustrate the study selection

process

Eur Child Adolesc Psychiatry (2013) 22:203–216 207

123

placebo (Fig. 2) showed a mean increase of 9.72 %

(p \ 0.001) in observed on-task behaviour whilst a pooled analysis of high-dose methylphenidate versus placebo

(Fig. 3) demonstrated a mean increase of 14.04 %

(p \ 0.001). Furthermore, five studies found that on-task behaviour was increased as a function of increasing dose of

methylphenidate [45, 62, 66, 73, 74].

Higher doses of methylphenidate were found to substan-

tially increase on-task behaviour [49, 66, 73, 74], with high-

dose showing a mean increase of 2.96 % (p \ 0.001) over low-dose in the percentage of intervals during classroom

observation that children were observed to be on-task (Fig. 4).

Mixed amfetamine salts (Adderall �

)

A pooled analysis of two studies [38, 39] assessing the

effects of mixed amfetamine salts on on-task behaviour

found a mean increase of 9.19 % (p \ 0.001) in children

Fig. 2 A forest plot of studies comparing the effect of MPH low-dose (0.3 mg/kg or 10 mg fixed-dose) against placebo on on-task behaviour

Fig. 3 A forest plot of studies comparing the effect of MPH high-dose (0.6 mg/kg or 17.5–20 mg fixed-dose) against placebo on on-task behaviour

Fig. 4 A forest plot of studies comparing the effect of MPH low-dose (0.3 mg/kg or 10 mg fixed-dose) against MPH high-dose (0.6 mg/kg or 17.5–20 mg fixed-dose) on on-task behaviour

208 Eur Child Adolesc Psychiatry (2013) 22:203–216

123

receiving mixed amfetamine salts compared to placebo

(Fig. 5).

Academic performance

Methylphenidate

The effects of methylphenidate on academic performance

were examined in thirty studies. Of these, fifteen [36, 38, 39,

45, 46, 53, 57–63, 72, 74] measured seatwork productivity

and fourteen [36, 38, 39, 45, 46, 54, 57–59, 61–63, 72, 74]

measured seatwork accuracy. Fourteen studies found that

methylphenidate was significantly different from placebo in

increasing the percentage of seatwork that children com-

pleted [18, 20, 21, 27, 28, 35, 36, 38–46, 53, 56–63, 74] with

low-dose methylphenidate (Fig. 6) resulting in a mean

increase in work completed of 11.76 % (p \ 0.001), and high-dose methylphenidate (Fig. 7) a mean increase of

14.40 % (p \ 0.001). However, only five studies [58, 59, 62, 63, 66] found that methylphenidate increased the per-

centage of seatwork that children completed accurately, and

a pooled analysis of eight studies (Fig. 8) showed no sig-

nificant effect of low-dose methylphenidate compared to

placebo on children’s seatwork accuracy.

Fig. 5 A forest plot of studies comparing the effect mixed amfetamine salts (Adderall �

) against placebo on on-task behaviour

Fig. 6 A forest plot of studies comparing the effect of MPH low-dose (0.3 mg/kg or 10 mg fixed-dose) against placebo on percentage seatwork children completed

Fig. 7 A forest plot of studies comparing the effect of MPH high-dose (0.6 mg/kg or 17.5–20 mg fixed-dose) against placebo for percentage seatwork completed

Eur Child Adolesc Psychiatry (2013) 22:203–216 209

123

Six studies assessing the effects of methylphenidate on

the PERMP test showed that methylphenidate increased the

number of questions attempted and correct [40, 44, 47, 56,

64, 69].

Of the eleven studies using independent arithmetic tests

[45, 48, 50, 55, 57, 58, 65, 68, 71, 72, 76], all but one [72]

reported increased questions attempted and eight reported

an increase in questions correct [48, 50, 57, 58, 65, 68, 71,

76] with drug. The ten studies that used a variety of aca-

demic measures including grade averages and other count-

ing, reading and spelling measures yielded more variable

results, with seven studies reporting an improvement in

work attempted and correct [42, 50–52, 58, 59, 63] and three

reporting no significant overall effects [45, 48, 75].

No studies reported a significant difference between

methylphenidate standard-release and methylphenidate

extended-release on any measures except the duration of

action, where Dopfner et al. [47] reported that extended-

release methylphenidate produced a significantly greater

improvement than standard-release methylphenidate in

PERMP scores when measured at the end of a school day

[47]. Studies that examined extended-release preparations

found significant improvements in productivity (work

completion or PERMP attempted) and accuracy (percent-

age seatwork or PERMP correct) [47, 59], whilst studies

that examined transdermal patches uniformly showed

improvement in productivity, but were inconsistent in

finding an improvement in accuracy [56, 61].

Of the twenty-three studies assessing different doses of

methylphenidate [38, 39, 41, 43, 45, 46, 49, 51–53, 57, 60–

63, 65, 66, 68, 69, 71, 73–75], four did not report between-

dose comparisons [53, 60, 68, 69] and eleven [43, 49, 51,

52, 57, 62, 63, 65, 66, 73, 74] reported between-dose dif-

ferences in classroom outcomes, with five demonstrating a

significant linear relationship between increasing dose and

improvement in the outcome measures [51, 57, 62, 73, 74].

Descriptively, higher doses of methylphenidate were found

to significantly increase academic efficiency, [66, 73, 74]

seat work completion [62, 66], accuracy [62, 74] and maths

test accuracy [43, 65]; however, a pooled analysis of six

studies (Fig. 9) found no significant difference (p = 0.37)

between doses on the measure of percentage seatwork

completion. Studies comparing the effects of low-dose

methylphenidate versus high-dose methylphenidate on

seatwork accuracy did not present sufficient data for meta-

analysis.

Mixed amfetamine salts (Adderall�)

The effects of mixed amfetamine formulations were

assessed in six studies [36–40, 55]. Three studies found that

mixed amfetamine salts significantly increased both the

number of PERMP questions attempted and the number

correct [36, 37, 40]. A pooled analysis of two studies [38,

39] (Fig. 10) showed a significant (p \ 0.001) mean increase of 15.39 % in the percentage of seatwork children

completed compared to children receiving placebo. Neither

of these studies reported a significant effect on seatwork

accuracy, although sufficient data were not presented to

confirm this with a second pooled analysis. Only one study

reported no significant improvement in the number of

questions attempted or correct in an independent maths-test

with Adderall compared to placebo [55]. One study [37]

that assessed both Adderall �

and Adderall extended release

(Adderall XR �

) reported that both were associated with

improvements in the number of problems children

attempted and the number of problems they solved com-

pared to placebo, and that the different drugs had similar

time effects.

Three studies used different doses of mixed amfetamine

formulations [37, 39, 40]. Of these, two studies [37, 39] did

not report between-dose comparisons. One study [40] repor-

ted that increasing the dose of Adderall �

had a significant

effect (p = 0.001) on PERMP-attempted and -correct scores.

Fig. 8 A forest plot of studies comparing the effect of MPH low-dose (0.3 mg/kg or 10 mg fixed-dose) against placebo for work accuracy (percentage seatwork correct)

210 Eur Child Adolesc Psychiatry (2013) 22:203–216

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Dexamfetamine

All five studies assessing dexamfetamine reported signifi-

cant improvements in the amount of academic work com-

pleted with dexamfetamine relative to placebo [36, 50, 55,

59, 67]. Significant improvements were seen both in the

number of PERMP questions attempted and completed

(p \ 0.001) [18, 49] and in arithmetic and reading attempted and correct [50]. Similar results were observed

for both standard and extended-release dexamfetamine

[55]. However, whilst Pelham et al. [59] found a significant

effect of Dexedrine spansules (extended-release dexamfe-

tamine) on the percentage of seatwork completed and the

number of reading questions attempted, they did not find

similar results for accuracy measures [59].

Atomoxetine

Only two studies were found to assess the effects of ato-

moxetine on academic achievement [77, 78]. Brown et al.

[77] found no improvement in children’s APRS scores.

However, Wietecha et al. [78] reported contrasting results

with some statistically significant improvements in reading,

written language scores and maths grades, but a non-

statistically significant improvement in English, science

and social studies grades. Wietecha et al. [78] also com-

pared the effects of two different doses of atomoxetine and

found only a small statistically significant decrease in

broad maths scores in the high-dose group as compared to

the low-dose group (p = 0.040).

Between-drug comparisons

Three studies compared the effects of mixed amfetamine

formulations and methylphenidate [38–40]. Two reported

no significant differences between methylphenidate and

mixed amfetamine formulations [38, 39]. One [40] repor-

ted earlier peak effects and a shorter duration of action for

methylphenidate as compared to Adderall �

.

Although two studies assessed the effects of both

methylphenidate and dexamfetamine [50, 59], only one

reported between-drug differences, finding that partici-

pants attempted more (p \ 0.05) arithmetic questions on dexamfetamine (d-AMPH) than on methylphenidate

(MPH) [50] although the exact percentage was not stated.

Two studies assessed the effects of both mixed amfeta-

mine salts (Adderall �

) and dexamfetamine [36, 55]. One

study reported no significant differences between the

effects of mixed amfetamine salts and dexamfetamine

[55].

Of the studies which did not lend themselves to meta-

analysis due to insufficient data, twenty-six showed sig-

nificant beneficial effects (p \ 0.001 to p = 0.05) of medication [36, 37, 40, 42–44, 48, 50, 54–57, 62–64, 66–

74, 76, 78] and two showed non-significant beneficial

effects (p = 0.143) [75, 77]; in contrast one study [41]

found a detrimental effect of high-dose methylphenidate

on seatwork completed (p = 0.035) and of low-dose

methylphenidate on seatwork accuracy. The findings of

these studies are presented in more detail in Online

Resource 2.

Fig. 9 A forest plot of studies comparing the effect of MPH low-dose (0.3 mg/kg or 10 mg fixed-dose) against MPH high-dose (0.6 mg/kg or 17.5–20 mg fixed-dose) on percentage seatwork completed

Fig. 10 A forest plot of studies comparing the effect of mixed amfetamine salts (Adderall�) against placebo for percentage seatwork completed

Eur Child Adolesc Psychiatry (2013) 22:203–216 211

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Quality and heterogeneity

Assessment of study quality showed a lack of allocation

concealment in a large number of studies [38, 39, 41–43,

45–47, 49–51, 53, 54, 56–60, 62, 63, 65, 66, 68–71, 75, 77,

78], and inadequate action regarding missing participants

or missing outcome data in twenty-five of the studies [38,

41–43, 45–47, 49, 51–54, 58, 59, 61–63, 65, 66, 70, 71, 73,

74, 76, 78].

Four meta-analyses demonstrated the presence of sub-

stantial heterogeneity (summarized in Online Resource 3).

In all cases, except the comparison of low-dose MPH

versus placebo on on-task behaviour, excluding the outliers

reduced heterogeneity to \50 % and decreased the size of the effect estimate; however, in no cases did this change

the direction or significance of the effect estimate.

Discussion

Main findings

In terms of on-task behaviour in the classroom, the findings

from this review support the beneficial effects of treatment

with methylphenidate, mixed amfetamine formulations and

dexamfetamine for children with ADHD. Meta-analyses

demonstrated significant improvements with both methyl-

phenidate (high and low dose) and mixed amfetamine

formulations. Effects of treatment with atomoxetine were

inconclusive. Between-dose differences for methylpheni-

date were found by pooled analyses to be small and non-

significant; however, studies reviewed descriptively

showed more significant effects, with five studies [57, 62,

63, 73, 74] demonstrating a greater improvement with

high-dose methylphenidate, and two describing a linear

relationship between dose and improvement on the out-

come measures [57, 73]. Between-dose comparisons for

other drugs were inconclusive.

In terms of academic performance, this review has found

that drug treatment for ADHD benefited children in the

amount of assigned seatwork that they completed, across

three different drugs at both high and low doses. The meta-

analyses showed that both methylphenidate (low and high-

dose) and mixed amfetamine formulations improved the

amount of seatwork children completed. A pooled analysis

for low-dose methylphenidate showed a non-significant

effect on the amount of seatwork completed correctly. This

suggested that although drug treatment improved produc-

tivity in children, possibly via an improvement in their

on-task behaviour as discussed above, it did not affect

the overall accuracy of their seatwork. Effects of drug

treatment with atomoxetine were inconclusive on these

measures.

Studies that assessed other measures of academic

achievement described improvements with drug treatment

in both the amount of questions completed and the number

correct, most notably in arithmetic tests; results from

reading and spelling outcomes were less conclusive. This

suggests that drug treatment not only improved the amount

of academic work that children were able to complete, but

also affected the processing of certain types of work, such

as arithmetic, leading to improvements in children’s

accuracy in these areas. However, this effect of improved

accuracy was not consistent across different types of aca-

demic assignment.

Between-dose differences in seatwork completion for

methylphenidate were found by pooled analyses to be non-

significant. However, a descriptive summary of studies

examining between-dose differences did not reflect this,

with nearly two-thirds demonstrating an improvement with

high-dose methylphenidate over low-dose, and some

studies describing a linear relationship between dose and

improvement on the outcome measures. Between-dose

comparisons for other drugs were inconclusive. No studies

meeting inclusion criteria for this review examined

between-dose differences for dexamfetamine.

In terms of between-drug comparisons, the two differ-

ences found between drug treatment with methylphenidate

and mixed amfetamine formulations were in the duration of

action and the time taken to reach the peak drug effect; on

measures of academic productivity, accuracy and on-task

behaviour, the two drugs were found to be largely equiv-

alent. The examination of differences between the effects

of methylphenidate and dexamfetamine, and mixed amfe-

tamine salts and dexamfetamine, were less conclusive, with

only six studies making between-drug comparisons and a

variation in effects being seen; four studies reported no

difference between drugs, whilst one study reported a

significant improvement with dexamfetamine over meth-

ylphenidate on academic productivity, whilst one study

reported differences only in drug onset and duration of

action.

Strengths and weaknesses of the review

This review is the most recent to assess the effects of drugs

for ADHD on academic performance and assess the effects

of four drugs. In addition, the review included only RCTs

and where possible data have been extracted and manipu-

lated for inclusion in meta analyses. The search for liter-

ature was performed using both medical and educational

databases. Heterogeneity was assessed across all nine

meta-analyses but was substantial in one analysis. Heter-

ogeneity was therefore unlikely to have significantly

affected the overall direction or size of findings. Publica-

tion bias was not judged to be of major importance after

212 Eur Child Adolesc Psychiatry (2013) 22:203–216

123

analysis using funnel plots; however, the possibility cannot

be completely ruled out.

As far as we are aware, this systematic review is the first

to perform meta-analyses of the effects of drugs specifi-

cally on educational outcomes for children with ADHD.

Minimal restrictions were placed on study selection, with

no social, geographical or language restrictions, and the

review considered all subtypes of ADHD to enhance gen-

eralizability of findings. The review focussed on outcomes

measured in classrooms, therefore, findings will be of rel-

evance to real-world classroom situations.

Despite no limits being placed on language or country of

publication, included studies were almost exclusively from

the developed world. Studies were included irrespective of

the length of drug treatment and follow-up, thus results of

the review may differ according to duration of treatment.

Another limitation of this review was the need to impute

standard errors for some studies (as per the Cochrane

Handbook Sect. 16.4.6) [34]. Although the inclusion of

cross-over trials with calculation of the mean and standard

error of participant-specific differences between measure-

ments is contentious, this analysis appears to be under-

weighted rather than over-weighted, and therefore may be

considered appropriate. There were five studies [26, 39, 48,

55, 56] where data remained insufficient for this to be

possible; these could not be included in meta-analyses, and

were summarized descriptively. The absence of the results

from these studies in the meta-analyses may have affected

the size of the effect estimates. However, descriptive

findings from these studies support the effect directions

demonstrated in the corresponding meta-analyses; thus,

this is unlikely to have affected conclusions drawn in this

review.

Differences between studies in the definition of various

outcomes may have represented a risk of bias, by produc-

ing variability in results. With consideration of the overall

risk of bias in all studies (as per guidance in the Cochrane

Handbook Sects. 8.1–8.7 [34]), it is possible that the results

of the review remain unbiased. There were a number of

limitations to the studies included in the review, and

associated risks of bias are presented in Online Resource 4.

Several studies used participants known to have a previous

positive response to stimulant medication, or excluded

known non-responders, which may have led to a greater

positive response to drug treatment than would have been

normally expected. In studies where drugs were adminis-

tered at home, variations in adherence and time of first dose

may have affected outcomes. In addition, there is the

possibility of a ceiling effect on accuracy of assigned

seatwork, with work set at a level deemed suitable for the

child thus offering no room for improvement, which may

have been partially responsible for the lack of drug effects

observed for measures of accuracy.

Several included studies failed to control for the influ-

ence of order; as all but one of the studies included in the

review used a cross-over design, the order in which a

participant received each treatment may have influenced

their response according to which drugs they had already

received. Few studies were judged to have carried out

suitable allocation concealment; this may have resulted in

subversion, and introduced selection bias, which could

have resulted in a greater measured efficacy of drugs than

was actually the case. A number of studies used analogue

or laboratory classroom settings which may not accurately

represent a standard classroom setting and may have

altered children’s observed behaviour; however, it is rea-

sonable to expect that any influence would be the same

across all drug-groups.

Comparisons with previous reviews

Findings from previous reviews assessing the effects of

drugs on educational outcomes for children with ADHD

have been inconsistent. The findings of this review are

contrary to some reviews, including Schachar [23] and

Jadad et al. [22], who found that studies of long-term

treatment with stimulants provided little evidence for

improved academic performance. However, the review by

Schachar [23] was based on only 17 studies with the

authors rating only five as of adequate methodological

quality, and with insufficient data for meta-analysis. Sim-

ilarly, Jadad et al. [22] included only twenty-three studies

that compared drug differences, and did not combine these

studies quantitatively. The present review includes a

number of papers published post-Schachar’s [23] review,

focuses on both seatwork completed and accuracy, and

most notably is able to present a quantitative analysis of

studies suggesting an overall improvement in academic

performance with drugs.

Implications for further research and practice

This review was unable to usefully analyse the effects of

atomoxetine, as there was insufficient literature available

that fulfilled inclusion criteria for the review; neither was it

able to elaborate on the differences between drugs or

between-dose differences for any drugs except methylphe-

nidate, due to a lack of studies making such comparisons.

Future studies that assess educational outcomes using

atomoxetine, a non-stimulant drug, which may be consid-

ered preferable to stimulant drugs due to its lower abuse

potential, would be beneficial. Clinical trials that include

educational outcomes are also needed that directly compare

different drug treatments for ADHD. The findings from

between-drug comparisons would allow conclusions to be

drawn regarding which drug is superior for providing

Eur Child Adolesc Psychiatry (2013) 22:203–216 213

123

educational benefits. It would be beneficial for clinical

trials to establish the lowest optimum dose per kilogram

bodyweight for various ADHD drug treatments when

considering their effects on educational outcomes.

It is essential that future trials include outcomes that

focus on the accuracy of children’s academic work, to

establish whether drug treatment for ADHD is beneficial in

improving children’s ability in completing work correctly.

Trials should aim to use standardized and validated out-

come measures for assessing outcomes to promote com-

parison between study findings.

Conclusions

This review aimed to describe and analyse the effects of

methylphenidate, dexamfetamine, mixed amfetamine for-

mulations and atomoxetine on children’s classroom learn-

ing behaviour and academic performance. Despite the

potential risk of confounding and bias introduced by limi-

tations of the included studies, the meta-analysis provides

support for positive effects of psychopharmacological

interventions on academic success in children with ADHD.

The findings indicate that drug treatment for ADHD

improves the school experience for children both in terms of

their classroom behaviour and their academic performance.

Acknowledgments KS is partly funded by the NIHR Collaboration for Leadership in Applied Health Research and Care (CLAHRC) for

Nottinghamshire, Derbyshire, Lincolnshire. VP is funded by the

NIHR as a Doctoral Research Fellow and was previously funded by

the NIHR as an In-Practice Fellow.

Conflict of interest None.

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