Research Paper

Noninvasive brain stimulation in children and adults

with attention-deficit/hyperactivity disorder:
a systematic review and meta-analysis
Samuel J. Westwood, PhD; Joaquim Radua, PhD; Katya Rubia, PhD

Background: Repetitive transcranial magnetic stimulation (rTMS) or transcranial direct current stimulation (tDCS) could provide
treatment alternatives to stimulant medication for attention-deficit/hyperactivity disorder (ADHD), given some evidence for improve-
ments in cognition and clinical symptoms. However, despite a lack of solid evidence for their use, rTMS and tDCS are already
offer­ed clinically and commercially in ADHD. This systematic review and meta-analysis aimed to critically appraise rTMS and tDCS
studies in ADHD to inform good research and clinical practice. Methods: A systematic search (up to February 2019) identified
18 studies (rTMS 4, tDCS 14; 311 children and adults with ADHD) stimulating mainly the dorsolateral prefrontal cortex (dlPFC). We
included 12 anodal tDCS studies (232 children and adults with ADHD) in 3 random-effects meta-analyses of cognitive measures of
attention, inhibition and processing speed. Results: The review of rTMS and tDCS showed positive effects in some functions but not
others, and little evidence for clinical improvement. The meta-analyses of 1 to 5 sessions of anodal tDCS over mainly the left or bi-
lateral dlPFC showed trend-level improvements in inhibition and processing speed, but not in attention. Limitations: Heterogeneity
in stimulation parameters, patient age and outcome measures limited the interpretation of findings. Conclusion: The review and
meta-analysis showed limited evidence that 1 to 5 sessions of rTMS and tDCS, mostly of the dlPFC, improved clinical or cognitive
measures of ADHD. These findings did not support using rTMS or tDCS of the dlPFC as an alternative neurotherapy for ADHD as
yet. Larger, multi-session stimulation studies identifying more optimal sites and stimulation parameters in combination with cognitive
training could achieve larger effects.

Introduction lateral prefrontal cortex (dlPFC) and striatal and pari-

etal regions during attention;6 the bilateral superior pre-
Attention-deficit/hyperactivity disorder (ADHD) is defined frontal regions during working memory; 7 the inferior
by age-inappropriate and impairing symptoms of inatten- frontal, parietal and cerebellar regions during timing pro-
tion, hyperactivity and impulsivity.1 It is one of the most cesses;8 and the ventromedial frontostriatal areas during
common childhood disorders, with a prevalence of approxi- reward-related functions.9
mately 7%; problems persist into adulthood in the majority The most effective short-term treatment for ADHD is
of cases, and ADHD is associated with poor academic and with psychostimulant medications, 10 but they have side
social outcomes.2 ­effects and limited longer-term efficacy.11 Alternative treat-
Patients with ADHD have cognitive deficits, most promi- ments, including behavioural therapies, cognitive training,
nently in executive functions, such as motor and interference neurofeedback or dietary interventions, have shown lim-
inhibition, selective and sustained attention, working mem- ited efficacy.12–14
ory and switching, as well as in timing processes and reward- Noninvasive brain stimulation treatments, such as repeti-
based decision-making.3,4 tive transcranial magnetic stimulation (rTMS) and transcra-
Furthermore, meta-analyses of functional MRI (fMRI) stud- nial direct current stimulation (tDCS), are promising because
ies in ADHD show underactivation in different cognitive- they can stimulate key brain dysfunctions that have been
domain-dependent frontostriatal and frontocerebellar sys- ­established in ADHD over the last 2 decades of fMRI re-
tems, such as the right inferior and medial prefrontal and search.9 They are also relatively safe, with minimal side
striatal regions during cognitive control;5,6 the right dorso- ­effects; they are cheaper than long-term drug treatments or

Correspondence to: S.J. Westwood, Department of Child and Adolescent Psychiatry PO46, Social, Genetic and Developmental Psychiatry
(SGDP) Centre, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, 16 De Crespigny Park, London, SE5 8AF,
United Kingdom; [email protected]
Submitted Oct. 28, 2019; Revised Feb. 6, 2020; Accepted Feb. 29, 2020; Early-released Oct. 1, 2020
DOI: 10.1503/jpn.190179

© 2021 Joule Inc. or its licensors

E14 J Psychiatry Neurosci 2021;46(1)

 Brain stimulation in ADHD

fMRI neurofeedback, for example; and, more importantly, There has been an increase over the last decade of 18 rTMS
they can induce neuroplasticity,15 providing hope for longer- and tDCS studies in ADHD. Studies have used relatively het-
term effects, which drugs do not offer.9 erogenous stimulation protocols, as well as clinical and cogni-
In rTMS, rapid magnetic pulses are delivered to the scalp tive outcome measures, and have reported mixed positive and
with a wire coil to generate an electric current in the brain via negative effects on cognition and ADHD symptoms.9,37 Fur-
electromagnetic induction. The induced electrical current can thermore, knowledge is lacking with respect to optimal stimu-
trigger action potentials in a focal cortical region under the coil, lation protocols for children with ADHD (such as stimulation
and when pulses are administered at a particular frequency, frequency, intensity or stimulation site), and there are neuro-
rTMS can modulate neural activity with longer-lasting after- ethical concerns about potential costs to nontargeted func-
effects. In general, high-frequency rTMS (5 to 20 Hz) promotes tions.38 Despite these shortcomings, however, noninvasive
cortical excitability, and low-frequency rTMS (1 Hz) inhib- brain stimulation is already offered in private clinics in several
its cortical excitability.15 Longer-term clinical improvements countries and is available commercially and online.39,40
with rTMS have been demonstrated in several psychiatric dis- A recent meta-analysis of 10 tDCS studies in ADHD (n =
orders: up to 3 months in obsessive–compulsive disorder 201) found that predominantly anodal tDCS of the dlPFC led
when stimulating prefrontal, orbitofrontal and supplementary to a significant but small improvement in measures of inhibi-
motor regions;16 4 months in schizophrenia when stimulating tory control (Hedges’ g = 0.12, 95% confidence interval [CI]
temporoparietal regions;17 and 12 months in major depressive 0.01–0.24), and to a significant but moderate improvement in
disorder when stimulating the dlPFC,18–20 supporting its reaction times in n-back tasks in a smaller meta-analysis of
neuro­plastic potential. Relative to tDCS, rTMS has greater 7 effect sizes derived from 3 studies (Hedges’ g = 0.66, 95% CI
specificity in targeting neural regions,21 but it is more expen- 0.17–1.25).41 However, effect size estimates may have been in-
sive because of device costs and extensive user-training re- flated, because 2 studies reporting mostly null effects were
quirements.22–24 The most common adverse effects are transient not included;42,43 multiple dependent effects were clustered in
scalp discomfort underneath the coil as a result of stimulation the meta-analyses, unduly reducing variation between effect
of the pericranial muscles and peripheral nerves.25,26 sizes and overestimating statistical significance;44,45 and the
In tDCS, a weak direct electric current is passed between analysis of inhibitory control measures included noninhibi-
2 electrodes (a positive anode and a negative cathode) placed tory measures, such as inattention (e.g., omission errors), pro-
on the scalp. The current modulates spontaneous discharge cessing speed (e.g., reaction times to go trials) and reaction
rates and therefore neuronal network activity by causing sub- time variability, calling into question the specificity of the
threshold polarity-dependent shifts in resting membrane po- positive tDCS effects to the domain of inhibitory control.
tentials, with net increases (anodal stimulation) or decreases We therefore considered it paramount and timely to con-
(cathodal stimulation) in the excitability of underlying neur­ duct a systematic review of rTMS and tDCS studies and a
ons, leading to respective increases or decreases in cortical meta-analysis of tDCS studies in ADHD that included all
function and synaptic strength.27 Although tDCS is a rela- available empirical studies and controlled for multiple de-
tively new form of noninvasive brain stimulation, there is pendent effects and potential bias; that clustered cognitive
­evidence that it can enhance cognitive functions in healthy ­effects into clearly separated cognitive domains of inhibitory
controls,28 with longer-term effects of up to 9 or 12 months.29,30 control, attention and processing speed to elucidate effects of
In psychiatric disorders, positive clinical effects have been tDCS on specific cognitive domains; that tested the replicabil-
observed typically up to 1 month after stimulation (for re- ity of meta-analysis results with jackknife sensitivity analy-
views, see Moffa and colleagues,31 Tortella and colleagues32 ses; and that included further sensitivity analyses to reduce
and Kekic and colleagues),33 although it is possible that heterogeneity caused by studies with designs that deviated
­effects are longer-term. However, overall, tDCS effects are from the majority.
­often small, especially when administered in single sessions This review and meta-analysis aimed to provide a critical
in healthy controls.34,35 Relative to rTMS, tDCS is cheaper, appraisal of the most consistent clinical and cognitive effects
easier to use and produces relatively less discomfort; the of rTMS and tDCS in ADHD, scrutinizing the quality of the
most common adverse effects are mild transient tingling, studies, outlining limitations in the field and discussing
itching and reddening of the skin underneath the electrodes.36 neuro­ethical concerns and future directions, with the ulti-
Both rTMS and tDCS potentiate cellular and molecular mate aim of guiding clinical practice.
mechanisms involved in use-dependent local and distant syn-
aptic plasticity (e.g., γ-aminobutyric acid [GABA] and glutamate- Methods
mediated long-term potentiation), which may lead to longer-
term effects.20 This systematic review and meta-analysis Eligibility criteria
focuses on the clinical and cognitive benefits of rTMS and
tDCS, because they are the most investigated noninvasive The systematic review followed Preferred Reporting Items in
brain stimulation methods in ADHD. To our knowledge, other Systematic Reviews and Meta-Analyses (PRISMA) guide-
methods have not been as well investigated or applied in clin­ lines46 (Fig. 1; PRISMA checklist, Appendix 1, available at jpn.
ical settings in ADHD (e.g., intermittent or continuous theta ca/190179-a1). Inclusion criteria were as follows: empirical
burst stimulation, transcranial alternating current stimulation studies with sufficient method details that applied rTMS or
or transcranial random noise stimulation). tDCS in children and/or adults with ADHD confirmed by

J Psychiatry Neurosci 2021;46(1) E15

Westwood et al.

e­ ither a clinical diagnosis (as defined by DSM/ICD criteria) Search strategy

or by meeting cut-off criteria for ADHD on validated ADHD
rating scales or research diagnosis questionnaires (e.g., We searched Web of Knowledge, Scopus, PubMed, Ovid,
­Conners’ Adult ADHD Rating Scale t score > 6547 or the Kid- Google Scholar, psyarxiv and bioRxiv (up to the end of
die Schedule for Affective Disorders and Schizophrenia48). To February 2019) using the following keywords: “noninva-
avoid language bias, we did not exclude studies published in sive brain stimulation,” “transcranial electric stimulation,”
a language other than English, unless the paper could not be “transcranial direct current stimulation,” “tDCS,” “transcra-
accessed and/or translated by the authors of the article. Rele- nial magnetic stimulation,” “rTMS” or “transcranial electric
vant outcome measures included clinical measures of ADHD stimulation,” each in combination with “hyperkinetic disor-
and performance measures on cognitive tasks. der,” “attention-deficit/hyperactivity disorder,” “ADHD,”

Literature search: Web of Knowledge, Scopus, PubMed, Ovid, Google Scholar,

psyarxiv and bioRxiv (until February 2019)
Identification

Records identified through Additional records identified

database searching through other sources
(n = 16 778) (n = 3)

Records after duplicates removed

(n = 14 177)
Screening

Records screened
Records excluded (n = 2572)
(n = 2601)

Full-text articles assessed for eligibility Full-text articles excluded, with reasons
Eligibility

(n = 29) (n = 11)

Studies included in
qualitative synthesis
(n = 18)
Included

Studies included in
meta-analysis
(n = 12)

Fig. 1: Preferred Reporting Items in Systematic Reviews and Meta-Analyses (PRISMA) flow diagram of study selection.

E16 J Psychiatry Neurosci 2021;46(1)

 Brain stimulation in ADHD

“inattention,” “hyperactivity” or “impulsivity.” We also factors that comprise measures of attention, inhibition and
hand-searched the reference lists of retrieved articles and re- processing speed.53–56 Accordingly, for attention measures,
views. One author (S.J.W.) and an additional reviewer we included the numbers or percentages of errors or omis-
(S.W.H.) carried out the search separately; another author sion errors (or the inversely reported number or percentage
(K.R.) crosschecked the results. of correct trials) and intrasubject reaction time variability or
intrasubject coefficient of variation (intrasubject reaction time
Study selection variability divided by mean reaction time) to go/congruent/
target trials in go/no-go tasks, flanker tasks, Stroop colour
After removing all duplicates, 1 author (S.J.W.) and an addi- and word tasks (Stroop), working memory tasks and the
tional reviewer (S.W.H.) independently screened titles and Wisconsin Card Sorting Task (WCST). For inhibition meas­
abstracts. The full text of the remaining studies determined ures, we included the numbers or percentages of commission
final inclusion in accordance with our eligibility criteria. Of errors (or the inversely reported number or percentage of
the 16 778 studies identified, 14 177 duplicates and 2572 irrele- correct trials) to no-go trials in the go/no-go task; the number
vant papers were excluded after screening titles and ab- of percentage errors or reaction time to incongruent trials in
stracts. A full-text review of the remaining 29 studies resulted flanker or Stroop tasks; the number of commission errors in
in the exclusion of a further 11 studies, including 1 rTMS continuous performance tasks (CPTs) or MOXO tasks; stop
study written in Arabic, because the paper could not be ac- signal reaction times in the stop task; perseverative errors in
cessed and a translation could not be obtained from the the WCST; and multi-button responses in the MOXO task.
­­authors49 (Appendix 1, Table S1). This resulted in 18 peer-­ For processing speed, we included mean reaction times to
reviewed, published studies (4 rTMS and 14 tDCS; total go/congruent/target trials in alertness, CPT, go/no-go and
ADHD sample = 312), of which 12 anodal tDCS studies (total MOXO tasks, and completion time in the WCST.
n = 232) were eligible for meta-analysis (for the list of ex- We estimated effect sizes using small-sample-corrected
cluded studies, see Appendix 1, Table S1). The final list of in- standardized mean differences (i.e., Hedges’ g),57 which cal-
cluded studies was agreed upon by consensus; any disagree- culated the difference in performance under sham versus
ments were resolved by another author (K.R.). ­anodal tDCS divided by pooled standard deviation to stan-
dardize the effect. We reported effects as positive if a cogni-
Risk of bias assessment tive outcome measure showed improvement with anodal
tDCS relative to sham stimulation, and as negative if it
We assessed risk of bias using the Cochrane Collaboration’s showed deterioration. We conducted all meta-analyses using
risk of bias tool,50 which rates risk of bias across 5 domains: random-effects models to account for heterogeneity (i.e., ef-
selection bias, performance bias, detection bias, attrition bias fect size variation between studies beyond that expected for
and other biases. Using this tool, S.J.W. and K.R. assessed risk sampling error alone).58 To provide a measure of heterogen­
of bias for all sham-controlled studies and resolved any dis- eity, we report the I2 value; I2 values of 75%, 50% and 25% re-
agreements by consensus. Because the tool is designed for flect high, moderate and low heterogeneity, respectively.59
randomized controlled trials, we excluded open-label When estimating Hedges’ g in crossover designs, we ac-
­trials51,52 to avoid undue inflation of bias across domains. We counted for the correlation between pre and post measures
included open-label trials in the systematic review for a com- (otherwise, there would have been an underestimation of the
plete overview of available empirical studies. effect sizes).57 Where multiple effects were reported from the
same sample, we created composite effect sizes by averaging
Meta-analysis effect sizes and decreasing variances, assuming correlation
across the different effects. Because tDCS studies did not re-
Because of the small number of included studies, neither the port these correlations, we estimated the crossover correla-
clinical effects of rTMS and tDCS (n = 2 for each) nor the cog- tion from reported t values (25 of 60 reported outcomes) de-
nitive effects of rTMS studies (n = 2) and cathodal tDCS (n = rived from analyses comparing anodal tDCS with sham
3) could be subjected to meta-analysis. Therefore, we con- stimulation, and we estimated the correlation across multiple
ducted a meta-analysis only on the cognitive effects of anodal dependent outcomes from an ongoing neurotherapy inter-
tDCS (12 studies) in ADHD. We calculated effect sizes from vention study in our laboratory with a sample of 74 adoles-
reported means and standard deviations or t and f values cents with ADHD tested before and after intervention in the
where possible. All data were extracted by S.J.W. We used Maudsley Attention and Response Suppression task battery,
Plot Digitizer to convert plotted data to numerical values (for including go/no-go tasks, CPTs, Simon tasks, time estima-
an example, see Westwood and Romani35), and we obtained tion tasks54 and the WCST. Specifically, we assumed a cor­
any unreported data by personal communication. All ex- relation of 0.629 between outcome measures for studies with
tracted data were cross-checked by K.R. crossover designs, and a correlation of 0.3 between the differ-
To reduce large heterogeneity, we clustered cognitive out- ent effects for composite effects. In addition, we conducted
come measures into 3 domains and analyzed them in 3 separate sensitivity analyses assuming crossover correlation of 0.407
meta-analyses. Such clustering of outcome measures into cogni- and 0.780 (the upper and low 95% CIs of the estimated cor­
tive domains was informed by factor analyses of executive- relation) and composite correlation of 0.1 and 0.5 to test
function measures of ADHD, which typically cluster into whether findings depended on our estimates.

J Psychiatry Neurosci 2021;46(1) E17

Westwood et al.

Finally, we used jackknife sensitivity analyses (i.e., re-

Conners’ CPT; D-KEFS;

ADHD = attention-deficit/hyperactivity disorder; ADHD-RS-IV = ADHD Rating Scale, Fourth Edition; CAARS = Conners’ Adult ADHD Rating Scales; CGI-I = Clinical Global Impression–Improvement scale; CPT = continuous performance
task; D-KEFS = Delis–Kaplan Executive Function System; dlPFC = dorsolateral prefrontal cortex; DSM-IV = Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition; MT = motor threshold; PANAS = Positive and Negative
peating the same analysis and excluding a different study

Affect Schedule; rTMS = repetitive transcranial magnetic stimulation; TOVA = Test of Variables of Attention; VAS = visual analogue scale; WASI = Wechsler Abbreviated Scale of Intelligence (selected subtests from the Wechsler Adult
finger oscillation tasks
Reminding Test; digit
each time) to establish the replicability of findings. To im-

symbol coding test;

Buschke Selective
Cognitive
prove homogeneity, we carried out additional sensitivity

WASI/WISC-IV;
analyses that excluded studies with overlapping sam-

Not tested

Not tested
ples,60–63 or studies with methods that deviated from the

TOVA
majority of studies, such as those including community par-

Outcome measures
ticipants with high ADHD symptoms on validated ADHD
ratings scales but without a clinical ADHD diagnosis;43,64

score [+]); VAS (inattention [+])‡

CGI-I scale; ADHD-RS-IV scale

those including adult samples with ADHD;42,65,66 those tar-

teacher-rated inattention [+])

PANAS (inattention [+], total

hyperactivity/impulsivity [+],
geting the right inferior frontal cortex (IFC);43,67 those report-

DSM-IV ADHD symptom

ing change scores (i.e., post minus pre differences) rather

checklist (parent-rated
Clinical*
than post scores only;66 those using multi-stimulation ses-
sions;60–62,65 those with effect sizes based on working mem-
ory or WCST tasks;61,68 or those using parallel rather than
crossover designs.62,66,67 Lastly, given that effect-size esti-

CAARS
mates might be inflated in studies with a high risk of bias,
we conducted meta-regression analyses to compare the
­effect sizes of studies with high versus low or unclear risk of

1680 pulses

1500 pulses

1980 pulses

2000 pulses
(on/off not
bias for each risk of bias domain (i.e., selection bias, per­

reported)
Duration

30 s off)

20 s off)

26 s off)
(2 s on,

(2 s on,

(4 s on,
formance bias, detection bias, attrition bias and other
­biases). All analyses were conducted by J.R.; meta-analysis
calculations were conducted using the function “rma” of
the “metafor” package version 2.1 in R version 3.6.69,70
Intensity,
% of MT
Stimulation protocol

100

120

100
90
Results

Literature review
Frequency,
Hz
20

18

10
1

rTMS studies
Two double-blind, crossover studies targeted the right
dlPFC. In 13 adults with ADHD, 1 session of 20 Hz rTMS
Sessions,

relative to sham significantly improved overall self-rated

20

10
n
1

inattention but not hyperactivity symptoms.71 In 9 adults

with ADHD, 10 daily sessions of 10 Hz rTMS relative to
sham showed no effect on self-rated clinical symptoms, nor
Bilateral
dlPFC†

dlPFC§

dlPFC†
Region

dlPFC
Right

Right
Left

on electroencephalography or executive-function meas­

Intelligence Scale); WISC-IV = Wechsler Intelligence Scale for Children, Fourth Edition.
ures.72 In a single-blind study in 21 adolescents with
ADHD, 20 daily sessions of 18 Hz deep rTMS over the bi-
not reported)
Adults (age

lateral dlPFC (n = 13) compared with sham (n = 9) showed

Active: 32
Sham: 30
Age, yr

7–12

no effect on self-rated clinical or cognitive measures of sus-

18

tained attention.73 An open-label trial in 10 children with ‡Small change from baseline of 0.25 and 1.16 on 5-point Likert scales.
ADHD showed fewer teacher-rated inattention and parent-
rated hyperactivity/impulsivity symptoms 1 week after
Sham: 13
Active: 9
Table 1: Clinical and cognitive effects of rTMS

5 daily sessions of 1 Hz rTMS of the left dlPFC compared

13

10
N

*Plus sign [+] = statistically significant improvement.

with baseline.52 However, without sham control conditions,

placebo effects could not be ruled out (Table 1).
sham-controlled,

sham-controlled,

sham-controlled,

tDCS studies
Double-blind,
Design
Single-blind,

Single-blind,

Fourteen studies tested tDCS in ADHD; 9 studies were

Open-label
crossover

crossover

double-blind, 4 studies were single-blind and 1 study was

parallel

§6 cm rostral to motor cortex.

†5 cm forward to MT point.

open-label. Ten studies tested children, and 4 studies

tested adults. Only 2 studies combined tDCS with cogni-
tive training (Table 2 and Table 3).
Gomez et al.52
Bloch et al.71

Paz et al.73

tDCS studies in children with ADHD

Weaver
et al.72
Study

Two single-blind, sham-controlled crossover studies in

20 high school students who scored above the clinical cut-off

E18 J Psychiatry Neurosci 2021;46(1)

 Table 2: Clinical and cognitive effects of tDCS (part 1 of 2)

Stimulation protocol Outcome measures

Mean Anode/ Sessions, Duration,

Study Design N age, yr cathode mA n Timing* min Clinical† Cognitive†
Children
Bandeira et al.51‡ Open-label 9 11 Left dlPFC/ 2 5 Online 28 PGI-I Visual Attention Test (TAVIS-3; omission
right SOA errors [+]); NEPSY-II-inhibition (switch
errors [+]); digit span task; Corsi cube task
Breitling et al.67 Single-blind, sham- 21 14 Right IFC/ 1 1 Online 20 Not tested Flanker task (incongruent trials: errors
controlled, crossover left cheek [+]¶,** and ICV [+]¶,††)
Left cheek/ 1 1 Online 20 Not tested Flanker task
right IFC
Munz et al.60 Double-blind, sham- 14 12 Left dlPFC/ 0.25 1 Offline 25 (5 on, Not tested Go/no-go task (go RT [+] and
controlled, crossover right cheek; 1 off) intrasubject RTV [+]); motor memory task;
right dlPFC/ alertness task
left cheek
Nejati et al.68 Double-blind, sham- 15 10 Left dlPFC/ 1 1 Offline 15 Not tested Go/no-go task; n-back (accuracy, RT [+]);
(experiment 1) controlled, crossover right dlPFC Stroop task (incongruent trials: errors [+]
and RT [+]); WCST (completion time [+])
Nejati et al.68 Double-blind, sham- 10 9 Left dlPFC/ 1 1 Offline 15 Not tested Go/no-go task; n-back (accuracy [+],¶
(experiment 2) controlled, crossover right SOA RT [+]**); WCST (total categories
completed [+], total errors [+],
perseverative errors [+])**
Right SOA/ 1 1 Offline 15 Not tested Go/no-go task (no-go accuracy [+])**;
left dlPFC n-back; WCST (total categories completed
[+], total errors [+] and perseverative
errors [+]¶)**
Prehn-Kristensen Double-blind, sham- 12 12 Left dlPFC/ 0.25 1 Offline 25 (5 on, Not tested Declarative memory task (accuracy [+]);

J Psychiatry Neurosci 2021;46(1)

et al.61 controlled, parallel right cheek; 1 off) alertness task; digit span task
right dlPFC/
left cheek
Soff et al.62 Double-blind, sham- 15 14 Left dlPFC/ 1 5 Online 20 FBB-ADHD QbTest (inattention [+]††;
controlled, crossover vertex (inattention hyperactivity [+]***)§§,¶¶
[+])‡‡,§§,¶¶
Soltaninejad et Single-blind, sham- 20 16 Left dlPFC/ 1.5 1 Online 15 Not tested Go/no-go task (go accuracy [+])¶,**;
al.64 controlled, crossover right SOA Stroop task
Right SOA/ 1.5 1 Online 15 Not tested Go/no-go task (no-go accuracy [+])¶,†††;
left dlPFC Stroop task
Soltaninejad et Single-blind, sham- 20 16 Right IFC/ 1 1 Online 15 Not tested Go/no-go task (go accuracy [+]);
al.43§ controlled, crossover left SOA Stroop task
Sotnikova et al.63 Double-blind, sham- 13 14 Left dlPFC/ 1 1 Online 20 Not tested QbTest (RT [+], RTV [+],‡‡‡
controlled, crossover vertex omission errors [−], accuracy [−])§§§

E19
Brain stimulation in ADHD
 Table 2: Clinical and cognitive effects of tDCS (part 2 of 2)

E20
Stimulation protocol Outcome measures

Mean Anode/ Sessions, Duration,

Study Design N age, yr cathode mA n Timing* min Clinical† Cognitive†
Adults
Westwood et al.

Allenby et al.65‡ Double-blind, sham- 37 32 Left dlPFC/ 2 3 Online 20 Not tested Conners’ CPT (commission errors [+]¶¶¶);
controlled, crossover right SOA stop task
Cachoeira et al.74 Double-blind, sham- Active: 9 Active: 31 Right 2 5 Offline 20 ADHD checklist Not tested
controlled, parallel Sham: 8 Sham: 34 dlPFC/ (inattention [+],
left dlPFC total [+])****;
SDS (after
tDCS only [+])
Cosmo et al.66 Double-blind, sham- Active: 30 Active: 32 Left dlPFC/ 1 1 Offline 20 Not tested Go/no-go task
controlled, parallel Sham: 30 Sham: 33 right dlPFC
Jacoby et al.42 Single-blind, sham- 20 23 Left and 1.8 1 Offline 20 Not tested CPT (multi-button presses [+])
controlled, crossover right dlPFC/
cerebellum

ADHD = attention deficit/hyperactivity disorder; CPT = continuous performance task; dlPFC = dorsolateral prefrontal cortex; FBB-ADHD = parents’ version of a German adaptive diagnostic checklist for ADHD; ICV = intrasubject coefficient
of variation; IFC = inferior frontal cortex; NEPSY-II = Neuropsychological Development Assessment, Second Edition; PGI-I = Patient Global Impression of Improvement; QbTest = Quantitative Behaviour Test; RT = reaction time;
RTV = reaction time variability or standard deviation of reaction times; SDS = Sheehan Disability Scale; SOA = supraorbital area; Stroop = Stroop colour and word task; tDCS = transcranial direct current stimulation; WCST = Wisconsin
Card Sorting Task.
*Refers to whether cognitive performance was during stimulation (online) or after stimulation (offline).
†Plus sign [+] = statistically significant improvement; minus sign [−] = statistically significant impairment.
‡Combined stimulation with cognitive training.
§Originally published in Persian; translated by the lead author (ZS).
¶Would likely not survive multiple comparison correction.
**Comparisons between stimulation conditions based on post-hoc least significant difference tests, which do not correct for multiple comparisons.
††Based on underpowered analysis focusing on the first session, with 7 participants per condition.
‡‡Improvement seen only 7 days after the fifth anodal tDCS session.
§§Did not survive correction for multiple comparisons.
¶¶Based on underpowered analysis focusing on the first 5 sessions, with 7/8 participants per condition.
***Improvement seen immediately after the fifth anodal tDCS session and 7 days later.
†††Significant in comparison to cathodal tDCS only.
‡‡‡Based on a crossover interaction; tDCS reduced RT and RTV in 1 of 4 conditions (2-back tasks), but this did not survive correction for multiple comparisons.
§§§Included carryover effect raised by Soff et al.62
¶¶¶Significant only immediately after anodal tDCS; not significant 3 days later.

J Psychiatry Neurosci 2021;46(1)

****Inattention improved immediately after anodal tDCS and after 2 weeks; total score improved only after 2 weeks.

per condition.
Stroop task measures.43
improvements on any other go/no-go or

dlPFC also improved no-go accuracy,

errors to incongruent trials, but had no

which have been associated with motor

found that 1 session of anodal (but not

response inhibition in children and

in 21 adolescents with ADHD, which

WCST performance; anodal tDCS had
measures. Furthermore, errors and reac-
effects on n-back accuracy or go/no-go
proved WCST completion time and
crossover studies applied single-session

ous paper, 68 findings were based on

compared to both sham treatment and
gruent trials) — the established key out-
eral dlPFC (anode left/cathode right) im-
stimulation over the dlPFC. In 15 adoles-

flanker task.67 However, as in the previ-

tion increasing right prefrontal regions,68
cathodal tDCS. Both anodal and cathodal
ing memory accuracy and reaction times
of the left dlPFC improved n-back work-
10 adolescents with ADHD, anodal tDCS
on Stroop − reaction time/errors on con-
go accuracy, but there were no equivalent
tDCS relative to sham treatment improved
ance on the Stroop task.64 Right IFC anodal
cathodal tDCS improved no-go accuracy
the left dlPFC improved go accuracy, and
IFC.43 Anodal relative to cathodal tDCS of
for ADHD on validated ADHD question-

reducing the sample size to 7 participants

effect, and the analysis included only the
flanker interference reaction time or error
flanker incongruent trials rather than on
cathodal) tDCS over the right IFC versus
ported by a single-blind crossover study
presumably via interhemispheric inhibi-

adults.54,75 This explanation is partly sup-

stronger effects. Cathodal tDCS of the left
come measure of the Stroop task. In
ence or error effect (reaction time/errors
measures, rather than the Stroop interfer-
tDCS over the left dlPFC64 or the right

first session to remove a practice effect,

sham treatment reduced errors (trend
level) and reaction time variability in a
n-back and Stroop reaction times and

tDCS over the left dlPFC improved

cents with ADHD, tDCS over the bilat-

Stroop task were used as main outcome

naires applied a single session of anodal

tion times to incongruent trials in the

Two double-blind, sham-controlled,
compared with anodal tDCS and sham
treatment, but none improved perform­
 Brain stimulation in ADHD

Table 3: Cognitive task measures (mean ± SD) extracted from studies (part 1 of 2)

Study Cognitive task Cognitive outcome measure tDCS, mean ± SD Sham, mean ± SD Effect*
Measures of attention
Allenby et al.65 CPT No. omission errors 1.9 ± 4.3 2.1 ± 2.4 Single
Breitling et al.67 Flanker task % Omission errors 2.2 ± 4.6 5.8 ± 7.6 Composite
(incongruent trials)
Flanker task Intraindividual coefficient of 0.2 ± 0.1 0.3 ± 0.1
(incongruent trials) variation (ms)†
Cosmo et al.66 Go/no-go task (fruits) No. omission errors (post/pre)‡ –2.9 ± 24.5 −3.7 ± 21.2 Single
Jacoby et al.42 MOXO task RT (ms) with 1 distractor 552.2 ± 53.9 558.9 ± 52.1 Composite
MOXO task RT (ms) with 2 distractors 556.5 ± 54.4 568.9 ± 53.5
MOXO task No. omission errors 4.2 ± 4.1 4.3 ± 4.0
Munz et al.60 Alertness task Intrasubject RTV (ms) 69.5 ± 25.1 76.1 ± 31.2 Composite
Go/no-go task (go trials) Intrasubject RTV (ms) 225.2 ± 246.9 379.4 ± 425.3
Go/no-go task (go trials) No. omission errors 3.0 ± 3.0 4.3 ± 4.4
Nejati et al.68 Go/no-go task (go trials) % Correct 93.3 ± 11.4 90.9 ± 19.6 Composite
(experiment 1) N-back task (1-back) No. correct 15.3 ± 8.3 14.4 ± 7.4
WCST No. of categories completed 2.5 ± 0.8 2.4 ± 1.1
WCST No. total errors 29.7 ± 8.3 30.7 ± 9.3
Nejati et al.68 Go/no-go task (go trials) % Correct 100 ± 0.0 98.5 ± 3.2 Composite
(experiment 2) N-back task (1-back) No. correct 21.0 ± 2.3 17.9 ± 2.9
WCST No. of categories completed 5.1 ± 0.7 3.9 ± 0.7
WCST No. total errors 11.0 ± 2.9 21.6 ± 5.4
Prehn-Kristensen Digit span task No. correct 9.6 ± 2.4 10.8 ± 2.1 Single
et al.61
Soff et al.62 QbTest (inattention) z-scores (omission errors, RT 0.1 ± 1.2 −0.1 ± 0.4 Single
and intrasubject RTV)
Soltaninejad et al.64 Go/no-go task (go trials) % Correct 98.8 ± 3.6 98.9 ± 1.9 Single
Soltaninejad et al.43 Go/no-go task (go trials)§ % Correct — — Single
Sotnikova et al.63 QbTest (overall) Intrasubject RTV (ms) 214.3 ± 97.2 235.2 ± 122.7 Composite
QbTest (overall) No. omission errors 38.6 ± 22.8 22.5 ± 15.3
QbTest (overall) % Correct¶ 31.7 ± 5.1 43.5 ± 6.9
Measures of inhibition
Allenby et al.65 CPT No. commission errors 17.1 ± 9.1 19.8 ± 10.9 Composite
Stop task Stop signal RT 288.4 ± 76.0 291.5 ± 68.1
Breitling et al.67 Flanker task RT (ms) 581.0 ± 43.0 585.0 ± 38.0 Composite
(incongruent trials)
Flanker task % Errors 9.8 ± 7.2 20.6 ± 9.2
(incongruent trials)
Cosmo et al.66 Go/no-go task (fruits) No. commission errors –5.5 ± 10.0 −6.9 ± 10.4 Single
(post/pre)‡
Jacoby et al.42 MOXO task Multi-button responses 4.7 ± 4.9 7.0 ± 6.3 Composite
MOXO task No. commission errors 11.3 ± 11.2 11.7 ± 12.1
Munz et al.60 Go/no-go task (no-go trials) No. commission errors 15.7 ± 10.3 12.6 ± 8.2 Single
Nejati et al.68 Go/no-go task (no-go trials) % correct 19.9 ± 7.6 19.0 ± 7.8 Composite
(experiment 1) Stroop task (incongruent trials) RT (ms) 2870 ± 2210 1390 ± 440
Stroop task (incongruent trials) % Errors 24.9 ± 12.0 34.9 ± 15.5
WCST No. perseverative errors 17.6 ± 3.6 18.0 ± 9.0
Nejati et al.68 Go/no-go task (no-go trials) % Correct 22.7 ± 1.3 20.7 ± 4.4 Composite
(experiment 2) WCST No. perseverative errors 7.8 ± 2.4 14.8 ± 3.7
Soff et al.62 QbTest (impulsivity) z-scores (commission errors, 0.2 ± 1.2 –0.2 ± 0.7 Single
multi-button press per
stimulus, anticipatory
button press)
Soltaninejad et al.64 Go/no-go task (no-go trials) % Correct 96.2 ± 8.2 95.8 ± 6.9 Composite
Stroop task (incongruent trials) % Correct 98.3 ± 2.9 96.4 ± 3.6
Stroop task (incongruent trials) RT (ms) 1080 ± 180 1130 ± 220

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Westwood et al.

Table 3: Cognitive task measures (mean ± SD) extracted from studies (part 2 of 2)

Study Cognitive task Cognitive outcome measure tDCS, mean ± SD Sham, mean ± SD Effect*
Soltaninejad et al. 43
Go/no-go task (no-go trials)§ % Correct — — Composite
Stroop task (incongruent trials)§ % Correct — —
Stroop task (incongruent trials)§ RT (ms) — —
Sotnikova et al.63 QbTest (overall) No. commission errors 6.0 ± 5.1 6.0 ± 4.2 Single
Measures of processing speed
Allenby et al.65 CPT RT (ms) to target 420.9 ± 63.3 419.7 ± 73.0 Single
Jacoby et al.42 MOXO task RT (ms) to target 541.5 ± 50.8 547.0 ± 53.5 Composite
Munz et al.60 Alertness task RT (ms) 309.6 ± 51.8 302.4 ± 44.3 Composite
Go/no-go task (go trials) RT (ms) 453.2 ± 131.3 566.9 ± 234.1
Nejati et al.68 Go/no-go task (go trials) RT (ms) 1080 ± 210 1030 ± 170 Composite
(experiment 1) N-back task (1-back) RT (ms) 120.2 ± 22.5 175.7 ± 55.4
WCST Completion time (ms) 237 300 ± 79 800 291 100 ± 106 700
Nejati et al.68 Go/no-go task (go trials) RT (ms) 1330 ± 900 1230 ± 120 Composite
(experiment 2) N-back task (1-back) RT (ms) 103.4 ± 24.2 162.9 ± 94.4
WCST Completion time (ms) 123 200 ± 16 900 170 300 ± 85 900
Soltaninejad et al.64 Go/no-go task (go trials) RT (ms) 830 ± 290 910 ± 350 Single
Soltaninejad et al.43 Go/no-go task (go trials)§ RT (ms) — — Single
Sotnikova et al.63 QbTest (overall) RT (ms) 555.3 ± 116.2 564.2 ± 130.8 Single

CPT = continuous performance task; QbTest = Quantitative Behaviour Test; RT = reaction time; RTV = reaction time variability; SD = standard deviation of the mean; Stroop = Stroop
colour word task; WCST = Wisconsin Card Sorting Task.
*For multiple effects from the sample, we created composite effect-size estimates; single effects otherwise.
†Intrasubject reaction time variability divided by mean reaction time.
‡Only change scores (post − pre/baseline) were reported.
§The author could not provide raw means and standard deviations for each stimulation condition, so to calculate Hedges’ g we converted the reported t-statistics.57
¶The % correct was reported as: hits (total no. of target trials − no. of omission errors errors) + correct rejections (total no. of no-go trials − no. of commissions errors)/total number of stimuli63

One double-blind, crossover study applied 5 daily sessions out a sham control condition, findings could have been con-
of anodal versus sham tDCS over the left dlPFC in 15 adoles- founded by placebo, test–retest or cognitive training effects.51
cents with ADHD. The results showed improvements relative
to sham treatment in parent-rated clinical measures of inatten- tDCS studies in adults with ADHD
tion and on cognitive measures of attention (as assessed using A double-blind, parallel study found no effects of a single
the QbTest, a combined working memory and go/no-go session of anodal tDCS over the left dlPFC relative to sham
task) 7 days after anodal tDCS but not immediately after, and treatment on go/no-go performance in 60 adults with
improvements in QbTest measures of hyperactivity both im- ADHD.66 A single-blind, crossover study in 20 undergradu-
mediately after anodal tDCS and 7 days later. Clinical and ates with ADHD found that 1 session of bifrontal anodal
QbTest impulsiveness measures showed no effects. However, tDCS over the left and right dlPFC relative to sham treatment
findings were based on the first 5 sessions to remove a carry- improved hyperactivity measures in a sustained attention
over effect, reducing the sample to 7 or 8 participants per con- task (i.e., multiple/random responses), but not omission er-
dition.62 In the same study, 13 of the 15 adolescents with rors or reaction times.42 A double-blind, crossover study in
ADHD showed reduced reaction time variability but in- 37 adults with ADHD found that 3 sessions over alternate
creased errors on the QbTest after a single session of anodal days of visual working memory training combined with
tDCS. However, this analysis included a carryover effect.63 ­anodal tDCS relative to sham tDCS of the left dlPFC reduced
A double-blind, sham-controlled crossover study found commission errors in a sustained attention task immediately
that relative to sham treatment, overnight slow-wave oscilla- after anodal tDCS, but not at the 3-day follow-up; there were
tory anodal tDCS over the left and right dlPFC improved de- no effects on omission errors, reaction times or stop task per-
clarative memory in 12 children with ADHD61 and go reac- formance immediately after anodal tDCS or 3 days later.65
tion time and its intrasubject variability in 14 children with ­Finally, a double-blind, parallel study in 17 adults with
ADHD,60 but had no effects on no-go accuracy, or on meas­ ADHD reported that 5 daily sessions of anodal right tDCS
ures of alertness, digit span or motor memory. (n = 9) relative to sham treatment (n = 8) improved inatten-
The only open-label trial in 9 children with ADHD found tion but not hyperactivity/impulsive symptoms immediately
that 5 daily sessions of anodal tDCS to the left dlPFC com- after stimulation and 2 weeks later, at which point the total
bined with a picture association cognitive training task re- ADHD score was also improved.
duced errors on attention (omission) and switch tasks but did
not improve working memory. Parents reported improve- Safety in tDCS studies
ments in some of their children’s behaviour except for one, Brain stimulation was well tolerated overall; the most com-
who reported their child was “much worse.” However, with- monly reported side effects were mild tingling and itching.

E22 J Psychiatry Neurosci 2021;46(1)

 Brain stimulation in ADHD

One study reported dropouts because of tingling sensations Meta-analysis of anodal tDCS studies
and headache43 (Table 4). There was 1 case of an adverse
­effect, where 1 patient reported hypobulia after a single ses- The majority of the studies included in the meta-analysis (10
sion of anodal tDCS over the right dlPFC, which persisted in of 12) used anodal stimulation of mostly left dlPFC regions
a milder form the following day.74 (unilateral left, n = 5; bifrontal anode left and right, n = 3; bi-
lateral anode left/cathode right, n = 2); only 2 studies in-
Summary of findings of tDCS studies volved unilateral stimulation of the right IFC (Table 2). The
Findings were mixed. With respect to the clinical effects of meta-analyses showed no significant effect in measures of at-
tDCS, only 2 sham-controlled studies tested and found im- tention (Hedges’ g = 0.18, 95% CI −0.19 to 0.45, p = 0.20) with
provement in behavioural symptoms of inattention but not high heterogeneity (I2 = 75%, p < 0.001) and trend-level im-
in impulsiveness/hyperactivity symptoms, and an open­ provements in measures of inhibition (Hedge’s g = 0.21, 95%
label trial found improvements in parent-rated impression CI −0.01 to 0.43, p = 0.06) with moderate heterogeneity (I2 =
of improvement in global functioning. Of 14 studies that 60%, p = 0.01) and of processing speed (Hedges’ g = 0.14, 95%
tested cognitive effects, 13 observed positive effects on some CI −0.01 to 0.29, p = 0.07) with low heterogeneity (I2 = 3%, p =
cognitive functions but not others, and 1 reported worse 0.50; Fig. 3). Sensitivity analyses confirmed that these find-
performance in a sustained attention task. 63 Moreover, ings did not systematically rely on our estimated correlations
7 sham-controlled studies did not correct for multiple com- for effects from crossover studies or for composite effect-
parisons,43,62–64,67,68 and the majority of their findings would size estimates (Appendix 1, Table S3). Further, we replicated
not have survived correction. these findings in the jackknife sensitivity analyses (i.e., re-
peating the main analyses but excluding a different study
Risk of bias with each repetition), with only minor exceptions: excluding
A minority of studies indicated unclear bias for selection (n = a minority of individual studies led to a significant but still
6), detection (n = 1) and attrition (n = 2), but on balance bias small effect in measures of inhibition (excluding Cosmo and
was low in these domains. Performance bias (i.e., blinding colleagues,66 Munz and colleagues60 and Soltaninejad and col-
participants and personnel) was unclear in 11 studies and leagues43) and in processing speed (excluding Allenby and
high in 2 studies; selective reporting bias and other biases colleagues65 and Soltaninejad and colleagues;43 Table 5).
(e.g., nonstandard outcome measures, no correction for mul- To improve homogeneity, we carried out additional sensi-
tiple testing, lenient significance threshold) were high in tivity analyses to exclude studies with overlapping samples,
4 studies (Fig. 2; Appendix 1, Table S2). methods that departed from the majority of studies or studies

Table 4: Side effects and adverse effects reported in studies using rTMS and tDCS

Study Side and adverse effects

rTMS studies
Bloch et al.71 Not tested, but authors observed differences in the somatosensory experience of real rTMS and sham, which limited true blinding
Gomez et al.52 Majority reported transient mild headache and scalp discomfort; a minority reported neck pain. No seizure-like cortical activity was
found. One case of slight and brief dizziness
Paz et al.73 Not tested
Weaver et al.72 Minority reported transient mild headaches and scalp discomfort
tDCS studies
Allenby et al.65 Burning, itching, pain and tingling were rated significantly higher during anodal tDCS compared with sham
Bandeira et al.51 Majority reported mild to moderate headache, tingling, itching, burning sensation and redness of the skin. Minority reported mild
neck pain, sleepiness and static shock. One parent reported child was “much worse” after stimulation
Breitling et al.67 Skin sensations were rated higher during cathodal tDCS relative to sham
Cachoeira et al.74 Comparable reports of headache, tingling, itching, burning sensation and tiredness were found in both sham and anodal tDCS.
One patient withdrew after the first sessions because of an “acute mood change, feeling sad, hypobulia, tension … 5 hours after
stimulation and persisted in a milder form into the next day”
Cosmo et al.66 None reported
Jacoby et al.42 Not tested, but authors reported that stimulation was well tolerated and no side effects were reported
Munz et al.60 Not tested, but no side effects were reported
Nejati et al.68 Reports of mild itching or tingling under electrodes
Prehn-Kristensen et al.61 Not tested. No side effects reported
Soff et al.62 About half of participants reported tingling and itching sensations under electrode during sham and anodal tDCS
Soltaninejad et al.64* Not reported
Soltaninejad et al.43* Several participants dropped out because of tingling sensation and headache
Sotnikova et al.63 About half of participants reported tingling and itching sensations under electrode during sham and anodal tDCS

rTMS = repetitive transcranial magnetic stimulation; tDCS = transcranial direct current stimulation.
*Personal communication, 2019.

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Westwood et al.

A Overall risk of bias ratings for rTMS studies (n = 3)

Random sequence generation (selection bias)

Allocation concealment (selection bias)
Blinding of participants and personnel (performance bias)
Blinding of outcome assessment (detection bias)
Incomplete outcome data (attrition bias)
Selective reporting (reporting bias)
Other bias

0% 25% 50% 75% 100%

Low risk of bias Unclear risk of bias High risk of bias

B Overall risk of bias ratings for tDCS studies (n = 13)

Random sequence generation (selection bias)
Allocation concealment (selection bias)
Blinding of participants and personnel (performance bias)
Blinding of outcome assessment (detection bias)
Incomplete outcome data (attrition bias)
Selective reporting (reporting bias)
Other bias

0% 25% 50% 75% 100%

Low risk of bias Unclear risk of bias High risk of bias

C Risk of bias ratings for individual studies

rTMS studies
Bloch et al.71 + ? – + + + +
+ Low risk of bias
Paz et al.73 + + ? + + ? +
? Unclear risk of bias
Weaver et al.72 + ? ? + + + +
– High risk of bias
tDCS studies
Allenby et al.65 + + – + + + +
Breitling et al.67 + ? ? + + – –
Cachoeira et al.74 + + ? + ? + +
Cosmo et al.66 + + ? + ? + +
Jacoby et al.42 + ? ? + ? + +
Munz et al.60 + + + + ? + +
Nejati et al.68 + + ? + ? – –
Prehn-Kristensen et al.61 + + + + + + +
Soff et al.62 + + ? ? ? ? ?
Soltaninejad et al.64 + ? ? + + – –
Soltaninejad et al.43 + ? ? + + – +
Sotnikova et al.63 + + ? + + – –
Random sequence generation (selection bias)
Allocation concealment (selection bias)

Blinding of participants/personnel (performance bias)

Blinding of outcome assessment (detection bias)
Incomplete outcome data (attrition bias)
Selective reporting (reporting bias)
Other bias

Fig. 2: Risk of bias ratings for (A) repetitive transcranial magnetic stimulation (rTMS), (B) transcranial direct current stimulation (tDCS) and (C)
individual studies. Note: risk of bias ratings were the same for both studies reported in Nejati et al.68

E24 J Psychiatry Neurosci 2021;46(1)

 Brain stimulation in ADHD

that were of lower methodological quality (Table 6). For inhi- CI 0.01 to 0.48, p = 0.04); or stimulated mainly the left dlPFC
bition measures, these analyses revealed significant but small (Hedges’ g = 0.24, 95% CI 0.01 to 0.47, p = 0.04), all of which
effects when the analysis was limited to studies using single- were associated with significant moderate heterogeneity (I2 =
session tDCS (Hedges’ g = 0.28, 95% CI 0.01 to 0.56, p = 0.04); 66, p = 0.01; I2 = 63, p = 0.01; I2 = 56, p = 0.02, respectively). For
reported only post-stimulation scores (Hedges’ g = 0.24, 95% processing speed measures, we found significant but small

A
Source Hedges’ g (95% CI) Favours sham Favours anodal tDCS
Allenby et al.65
0.06 (–0.26 to 0.38)
Breitling et al.67 0.77 (–0.11 to 1.66)
Cosmo et al.66 –0.04 (–0.54 to 0.47)
Jacoby et al.42 0.14 (–0.18 to 0.46)
Munz et al.60 0.38 (–0.02 to 0.78)
Nejati et al.68 (experiment 1) 0.09 (–0.26 to 0.44)
Nejati et al.68 (experiment 2) 1.43 (0.77 to 2.09)
Prehn-Kristensen et al.61 –0.57 (–0.19 to 0.05)
Soff et al.62 0.11 (–0.9 to 1.13)
Soltaninejad et al.64 –0.02 (–0.46 to 0.41)
Soltaninejad et al.43 0.6 (0.12 to 1.08)
Sotnikova et al.63 –0.43 (–0.85 to –0.01)

Total 0.18 (–0.09 to 0.45)

Heterogeneity: Q = 34.76 (p = 0); I² = 75% –2 –1 0 1 2 3

Test for overall effect: z = 1.28 (p = 0.20) Hedges’ g (95% CI)

B
Source Hedges’ g (95% CI) Favours sham Favours anodal tDCS
Allenby et al.65 0.17 (–0.09 to 0.44)
Breitling et al.67 0.66 (–0.22 to 1.53)
Cosmo et al.66 –0.13 (–0.64 to 0.38)
Jacoby et al.42 0.36 (0 to 0.73)
Munz et al.60 –0.36 (–0.91 to 0.18)
Nejati et al.68 (experiment 1) 0.42 (0.05 to 0.78)
Nejati et al.68 (experiment 2) 1.36 (0.61 to 2.11)
Soff et al.62 0.3 (–0.72 to 1.33)
Soltaninejad et al.64 0.33 (0 to 0.66)
Soltaninejad et al.43 –0.15 (–0.47 to 0.17)
Sotnikova et al.63 0.01 (–0.54 to 0.55)

Total 0.21 (–0.01 to 0.43)

Heterogeneity: Q = 23.56 (p = 0.009); I² = 60% –1 0 1 2 3

Test for overall effect: z = 1.9 (p = 0.06) Hedges’ g (95% CI)

C
Source Hedges’ g (95% CI) Favours sham Favours anodal tDCS
Allenby et al.65 –0.02 (–0.34 to 0.3)
Jacoby et al.42 0.12 (–0.32 to 0.56)
Munz et al.60 0 (–0.42 to 0.42)
Nejati et al.68 (experiment 1) 0.47 (0.08 to 0.87)
Nejati et al.68 (experiment 2) 0.37 (–0.1 to 0.85)
Soltaninejad et al.64 0.27 (–0.17 to 0.72)
Soltaninejad et al.43 –0.07 (–0.51 to 0.37)
Sotnikova et al.63 0.08 (–0.47 to 0.62)

Total 0.14 (–0.01 to 0.29)

Heterogeneity: Q = 6.37 (p = 0.50); I² = 3% –1 –0.5 0 0.5 1

Test for overall effect: z = 1.84 (p = 0.07) Hedges’ g (95% CI)

Fig. 3: Meta-analysis of measures of (A) attention, (B) inhibition and (C) processing speed. CI = confidence interval; tDCS = transcranial direct
current stimulation.

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Westwood et al.

effects when the analysis was limited to studies that used 1 study showed high risk of performance bias, we did not
­single-session tDCS (Hedges’ g = 0.22, 95% CI 0.04 to 0.41, p = carry out meta-regression analyses for these biases.
0.02), used child samples (Hedges’ g = 0.20, 95% CI 0.01 to
0.39, p = 0.04) or stimulated mainly the left dlPFC (Hedges’ Discussion
g = 0.17, 95% CI 0.01 to 0.33, p = 0.04), all of which were asso-
ciated with low heterogeneity (I2 = 0, p = 0.51; I2 = 9, p = 0.41; There has been a recent proliferation of noninvasive brain
I2 = 5, p = 0.50, respectively). stimulation studies in ADHD, with large heterogeneity in
Finally, meta-regression analyses compared the effect sizes methodology and outcome measures. We therefore con-
from studies with a high risk of reporting bias versus the ducted a systematic review of rTMS and tDCS studies. Fur-
­effect sizes from studies with low or unclear risk of such bias. thermore, we conducted a rigorous meta-analysis of tDCS
At a descriptive level, the effect sizes from studies with high studies in ADHD that clustered cognitive effects into clearly
risk of reporting bias or “other” biases (e.g., no correction to separated cognitive domains to increase homogeneity, con-
multiple testing, lenient α level) were larger than the effect trolled for multiple dependent effects and potential bias of
sizes from studies with low or unclear risk. These differences studies, and tested the replicability of meta-analysis results
were not statistically significant in any of the outcomes for re- with jackknife and other sensitivity analyses. The meta-analysis
porting bias (lowest p = 0.14), but “other” biases yielded a of tDCS studies of mostly the dlPFC showed only trend-level
significant effect in measures of inhibition (p = 0.03) and pro- effects on improvement of inhibition and processing speed,
cessing speed (p = 0.03). Because none of the studies showed but not on attention, suggesting limited effects of tDCS on
high risk of selection, detection or attrition bias, and only cognition in children and adults with ADHD.

Table 5: Results of jackknife sensitivity analysis

Effect size Heterogeneity

Meta-analysis Studies excluded Hedges’ g* 95% CI p value I 2

p value
Attention Allenby et al.65 0.19 –0.11 to 0.50 0.22 77 < 0.001
Breitling et al.67 0.14 –0.13 to 0.42 0.31 76 < 0.001
Cosmo et al.66 0.20 –0.10 to 0.50 0.19 78 < 0.001
Jacoby et al.42 0.19 –0.12 to 0.49 0.24 77 < 0.001
Munz et al.60 0.16 –0.14 to 0.46 0.30 77 < 0.001
Nejati et al.68 (experiment 1) 0.19 –0.12 to 0.50 0.22 77 < 0.001
Nejati et al.68 (experiment 2) 0.08 –0.12 to 0.27 0.43 49 0.040
Prehn-Kristensen et al.61 0.23 –0.03 to 0.50 0.09 72 0.001
Soff et al.62 0.18 –0.11 to 0.47 0.22 78 < 0.001
Soltaninejad et al.64 0.20 –0.10 to 0.50 0.19 77 < 0.001
Soltaninejad et al.43 0.14 –0.15 to 0.42 0.35 75 0.001
Sotnikova et al.63 0.24 –0.03 to 0.50 0.08 70 0.002
Inhibition Allenby et al.65 0.22 –0.04 to 0.48 0.09 65 0.010
Breitling et al.67 0.19 –0.03 to 0.41 0.10 62 0.010
Cosmo et al.66 0.24 0.01 to 0.48 0.040 63 0.010
Jacoby et al.42 0.20 –0.05 to 0.44 0.12 65 0.010
Munz et al.60 0.25 0.05 to 0.46 0.020 53 0.020
Nejati et al.68 (experiment 1) 0.19 –0.06 to 0.43 0.13 63 0.010
Nejati et al.68 (experiment 2) 0.15 –0.03 to 0.32 0.10 37 0.12
Soff et al.62 0.21 –0.02 to 0.44 0.07 65 0.010
Soltaninejad et al.64 0.20 –0.05 to 0.45 0.12 65 0.010
Soltaninejad et al.43 0.26 0.04 to 0.48 0.020 52 0.030
Sotnikova et al.63 0.23 –0.01 to 0.47 0.06 66 0.010
Processing Allenby et al.65 0.19 0.02 to 0.35 0.030 0 0.53
speed Jacoby et al.42 0.15 –0.02 to 0.32 0.09 13 0.38
Munz et al.60 0.16 0.00 to 0.33 0.06 10 0.44
Nejati et al.68 (experiment 1) 0.09 –0.08 to 0.25 0.29 0 0.79
Nejati et al.68 (experiment 2) 0.12 –0.04 to 0.28 0.15 2 0.50
Soltaninejad et al.64 0.13 –0.04 to 0.29 0.14 9 0.42
Soltaninejad et al.43 0.17 0.01 to 0.33 0.040 5 0.50
Sotnikova et al.63 0.15 –0.02 to 0.31 0.08 11 0.40

CI = confidence interval.
*Effect size estimates assumed a correlation of 0.629 for crossover studies and a correlation of 0.3 for multiple dependent effects.

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Table 6: Results for sensitivity analysis of the meta-analyses of attention, inhibition and processing speed

Effect sizes Heterogeneity

Included studies Excluded studies Studies Hedges’ g 95% CI p value I2 p value

Attention
All None 12 0.18 –0.19 to 0.45 0.20 75 < 0.001
Studies with crossover design Allenby et al.65; Breitling et al.67*; 9 0.17 –0.17 to 0.50 0.32 82 < 0.001
Soff et al.62
Patients with clinical ADHD diagnosis Soltaninejad et al.43; Soltaninejad et al.64† 10 0.16 –0.16 to 0.48 0.33 78 < 0.001
No WCST and working memory tasks Nejati et al.68‡; Prehn-Kristensen et al.61 11 0.14 –0.04 to 0.32 0.13 39 0.12
No overlapping samples§ Munz et al.60; Soff et al.62 10 0.16 –0.16 to 0.49 0.32 80 < 0.001
Munz et al.60; Sotnikova et al.63 10 0.22 –0.08 to 0.53 0.15 74 0.002
Prehn-Kristensen et al.61; Soff et al.62 10 0.24 –0.04 to 0.52 0.09 76 < 0.001
Prehn-Kristensen et al.61; Sotnikova 10 0.29 0.05 to 0.54 0.020 62 0.010
et al.63
Only single-session tDCS Allenby et al.65¶; Munz et al.60; 8 0.26 –0.11 to 0.64 0.17 81 < 0.001
Prehn-Kristensen et al.61; Soff et al.62
Report of post scores only Cosmo et al.66** 11 0.20 –0.10 to 0.50 0.19 78 < 0.001
Target site of dlPFC only Breitling et al.67††; Soltaninejad et al.43 10 0.10 –0.19 to 0.39 0.51 76 0.001
Only studies in children Allenby et al.65; Cosmo et al.66‡‡; 9 0.24 –0.16 to 0.63 0.24 80 < 0.001
Jacoby et al.42
Inhibition
All None 11 0.21 –0.01 to 0.43 0.06 60 0.01
Studies with crossover design Breitling et al.67*; Cosmo et al.66; 8 0.22 –0.04 to 0.48 0.09 71 0.004
Soff et al.62
Patients with clinical ADHD diagnosis Soltaninejad et al.43; Soltaninejad et al.64† 9 0.26 –0.02 to 0.53 0.07 62 0.02
No WCST and working memory tasks Nejati et al.68‡ 11 0.17 0.00 to 0.35 0.06 41 0.09
Only single-session tDCS Allenby et al.65¶; Munz et al.60; Soff et al.62 8 0.28 0.01 to 0.56 0.040 66 0.01
Report of post scores only Cosmo et al.66** 10 0.24 0.01 to 0.48 0.040 63 0.01
Target site of dlPFC only Breitling et al.67††; Soltaninejad et al.43 9 0.24 0.01 to 0.47 0.040 56 0.02
Studies in children only Allenby et al.65; Cosmo et al.66‡‡; 8 0.26 –0.08 to 0.60 0.13 72 0.004
Jacoby et al.42
Processing speed
All None 8 0.14 –0.01 to 0.29 0.07 3 0.50
Patients with clinical ADHD diagnosis Soltaninejad et al.43; Soltaninejad et al.64† 6 0.16 –0.02 to 0.34 0.09 13 0.40
No WCST and working memory tasks Nejati et al.68‡ 8 0.00 –0.16 to 0.16 1.00 0 0.78
Only single-session tDCS Cosmo et al.66¶; Munz et al.60 6 0.22 0.04 to 0.41 0.020 0 0.51
Target site of dlPFC Soltaninejad et al.43†† 7 0.17 0.01 to 0.33 0.040 5 0.50
Studies in children Allenby et al.65‡‡; Jacoby et al.42 6 0.20 0.01 to 0.39 0.040 9 0.41

ADHD = attention deficit/hyperactivity disorder; CI = confidence interval; dlPFC = dorsolateral prefrontal cortex; IFC = inferior frontal cortex; tDCS = transcranial direct current stimulation;
WCST = Wisconsin Card Sorting Task.
*These sudies used a parallel design; all others used crossover designs.
†Participants did not have a clinical diagnosis of ADHD.
‡Only WCST and working memory data excluded.
§To remove overlapping samples, we excluded 1 study at a time.
¶These studies applied tDCS over multiple sessions; all others used one session.
**The only studies to use change scores (post/pre stimulation scores), all other used post-tDCS scores.
††The only studies stimulated the right IFC; all other targeted the dlPFC.
‡‡Included adults; all others included children and adolescents.

The findings of the systematic review revealed that for measured clinical outcomes and found that anodal tDCS
rTMS, of the 4 included studies, only 2 measured and found over the left or right dlPFC improved ADHD inattention,
clinical effects, while the other 2 measured and found no but not impulsiveness/hyperactivity symptoms, immedi-
effects on cognitive functions. For tDCS, 12 of the ately after tDCS and 1 week62,74 or 2 weeks later.74 This
14 studies included in the systematic review stimulated the could suggest that dlPFC stimulation can improve clinical
dlPFC with anodal tDCS, mostly over the left hemisphere inattention in ADHD, but this finding will need to be con-
(unilateral left, n = 6; bilateral anode left/cathode right, firmed by future, larger studies.
n = 2; bifrontal left and right, n = 3), and 1 study applied Importantly, the rigorous meta-analysis of 12 tDCS studies
bilateral cathodal tDCS over the left dlPFC (anode right/ applying 1 to 5 sessions of anodal tDCS of mostly left or
cathode left), and 2 studies used unilateral anodal tDCS bilateral/bifrontal dlPFC (with the exception of Soltaninejad
over the right IFC. Only 2 sham-controlled tDCS studies and colleagues43 and Breitling and colleagues67) showed only

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Westwood et al.

trend-level improvements with small effect sizes in inhibi- can be enhanced with anodal tDCS over the right IFC, which
tion and processing speed, but no effects on attention. would be in line with neuroimaging evidence of a role of the
This systematic review of tDCS and rTMS studies showed right IFC in inhibitory control76,78,79,81,82,98–101 and evidence of its
that there is very limited evidence that rTMS and tDCS can underactivation in ADHD,5,6,9 as well as with tDCS studies in
have an effect on clinical symptoms based on a small sample healthy adults showing that right IFC stimulation improves
of 3 sham-controlled studies. The meta-analyses showed — motor inhibitory performance.85–88
albeit with small effect sizes — that 1 to 5 sessions of anodal The trend-level positive effect of tDCS of mostly the left
tDCS over mostly the left (but also bilateral and bifrontal) dlPFC on processing speed is in line with fMRI evidence in-
dlPFC improved performance on cognitive measures of dicating that the left dlPFC is a key mediating region of pro-
inhib­ition and processing speed, but there was no evidence cessing speed.102–104 Interestingly, when the processing speed
for improvement in attention measures. analysis excluded the only study stimulating the right IFC43
Given that 11 of 12 sham-controlled studies in the system- — and therefore included only studies stimulating mainly
atic review tested and found tDCS-induced improvement in the left dlPFC (unilateral left, n = 5; bilateral, n = 1; bifrontal
1 or more executive-function measures,42,43,60–65,67,68 the find- anodal left and right, n = 2)—the improvement in processing
ings of the meta-analysis may seem disappointing. However, speed became significant, in line with neuroimaging evi-
the lack of positive overall findings, despite positive findings dence that the left dlPFC mediates processing speed and sug-
in individual studies, was likely due to underpowered small gesting that the left dlPFC is an optimal site for enhancing
study effects that were uncorrected for multiple test- processing speed in ADHD. These findings are partly in line
ing43,62–64,67,68 and did not survive the scrutiny of meta-analysis. with those of the meta-analysis by Salehinejad and col-
The decision to cluster cognitive outcome measures into do- leagues,41 which showed that predominantly anodal tDCS
mains for the meta-analysis introduced additional hetero­ over the left dlPFC improved reaction times and its intra­
geneity, particularly in the attention and inhibition domains; subject variability in n-back tasks.
the processing speed domain was more homogeneous. The lack of systematic positive effects on attention meas­
The relatively small trend-level effect on inhibition may ures may have been because predominantly the right dlPFC
have been related to the fact that predominantly the right and IFC mediate attention, as evidenced by individual stud-
hemispheric IFC mediates inhibitory functions in children ies and meta-analyses of fMRI studies in children and
and adults,74,76–84 and that meta-analyses of fMRI studies in adults,77–79,84,105–107 and in meta-analyses of fMRI studies in
ADHD show underactivation of the right IFC during inhibi- ADHD, which show functional underactivation of the right
tion tasks.5,6 Stimulation of the right IFC may be more effec- dlPFC/IFC during attention tasks.6 It is therefore possible
tive for improving inhibitory functions in ADHD. This hy- that stimulation of the right dlPFC and/or right IFC may be
pothesis is supported by studies in healthy adults showing more effective for improving attention functions in ADHD.
that right IFC stimulation improves inhibitory perform­ This meta-analysis of tDCS studies shows that anodal tDCS
ance.85–88 The meta-analysis of Salehinejad and colleagues41 of mostly left dlPFC has only very limited, trend-level effects on
reported a similarly small, albeit significant, benefit (Hedges’ improving inhibition and processing speed, with no evidence
g = 0.12) with anodal tDCS of mostly the dlPFC on inhibitory for attention improvement. However, we cannot rule out the
measures, which survived when the analysis focused on ac- possibility that stimulation of other prefrontal regions (such as
curacy measures or only on studies stimulating the dlPFC. the right hemispheric IFC or dlPFC or parietal regions), multi-
However, Salehinejad and colleagues41 included multiple de- ple session tDCS or tDCS in combination with cognitive train-
pendent effects in their meta-analyses, which could have re- ing could improve clinical or cognitive functions in ADHD.
duced variation between effect sizes and therefore overesti- With respect to safety, stimulation was well tolerated over-
mated significance.44,45 Further, their meta-analysis included all, but 1 tDCS study reported higher errors on a sustained
noninhibitory measures of attention (e.g., CPT omission er- attention task63 and another study reported a hypobulia epi-
rors), processing speed (e.g., reaction times to go trials) and sode in 1 patient,74 raising neuroethical concerns of potential
reaction time variability,41 and therefore was not specific to costs to nontargeted functions.38,108 It has been shown that
inhibitory control, which could explain the differences in stimulation of a particular region could impair functions
findings compared to our meta-analysis. ­mediated by other regions such as the homologue contralat-
Although right IFC has been more clearly implicated in eral region via interhemispheric inhibition or other regions
motor response inhibition, the small, trend-level improve- that are top-down controlled by the stimulated region.109,110
ment in inhibition in our meta-analyses, in line with the small Future studies need to address the lack of knowledge about
significant effect of Salehinejad and colleagues,41 may have optimal stimulation protocols for children with ADHD. Cur-
been due to the fact that a majority of inhibitory measures rent knowledge about stimulation effects on the brain and
were derived from interference inhibition tasks, which have standard protocols are largely derived from adult samples
been shown to be co-mediated by the left dlPFC and IFC89 — and are therefore not appropriate for children.108,111 In healthy
in particular the Stroop task.90–93 Further, tDCS studies in adults, multi-session stimulation combined with cognitive
healthy adults have reported improved performance on in- training may lead to longer-term effects,30,112 but we do not
terference inhibition tasks following anodal tDCS of the left know whether this protocol can lead to maladaptive plasticity
dlPFC.94–97 Given that only 2 studies stimulated the right IFC, in the developing brain, especially during “sensitivity periods,”
future studies will have to test whether inhibition functions where use-dependent plasticity changes are strongest113 and

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 Brain stimulation in ADHD

the possibility of longer-term side effects when using nonin- this bias, meaning that summary effect size estimates might
vasive brain stimulation in pediatric samples needs more em- have been overestimated. In early rTMS studies, the same
pirical investigation. Future studies should heed recommen- research practices unduly inflated positive effects and
dations to comprehensively assess effects in children to slowed its uptake as an ­e ffective treatment of depres-
capture possible unintended outcomes.110,114 sion;124,125 the field risks doing the same with rTMS and tDCS
It should also be noted that the current findings refer only in ADHD. Moreover, with tDCS there is an added danger
to studies using 1 to 20 Hz rTMS and conventional tDCS of that children and parents — faced with apparent positive
dlPFC in ADHD. Other noninvasive brain stimulation proto- findings — will self-administer given the widely available
cols may be effective in ADHD, such as theta burst stimula- “do-it-yourself tDCS” material online or commercial de-
tion,115 transcranial alternating current stimulation,116,117 trans­ vices, one of which has been shown to impair working
cranial random noise stimulation118,119 or trigeminal nerve memory.40 Given the neuroethical concerns of brain stimula-
stimulation (TNS).120.121 tion with respect to potential negative effects on nontargeted
functions,38,108,114 future researchers are duty-bound to report
Limitations results to the highest possible standard.114
A final limitation of this meta-analysis is that it was not
Conclusive evidence of this systematic review of rTMS and preregistered.
tDCS and meta-analysis of anodal tDCS in ADHD is limited
by the large heterogeneity between studies with respect to Conclusion
stimulation protocols (coil/electrode placement, number of
sessions, stimulation intensity, crossover/parallel design), Based on current evidence, neither rTMS nor tDCS of the
sample age and cognitive outcome measures. dlPFC can be recommended as an alternative neurotherapy
Furthermore, limitations in individual studies were also for ADHD as yet. More studies are needed to assess clinical
present, such as tDCS electrode placement, low power, small efficacy, and the demonstrated cognitive effects have been
effect sizes, biased reporting or insufficient blinding. Specif­ small and nonsignificant. However, we cannot rule out the
ically, although all but 2 of 12 tDCS studies included in the possibility that rTMS or tDCS or other stimulation modal­
meta-analysis stimulated the left dlPFC, electrode placement ities of other regions — or even of the same region but
was bilateral (anode left/cathode right) in 2 studies66,68 and ­using a larger number of sessions, different amplitude or
bifrontal (anode left and right) in 3 studies.42,60,61 Bilateral or other par­ameters, or combined with cognitive training —
bifrontal tDCS could have had a neutral effect, given that the may be more effective. Furthermore, conclusive evidence
short inter-electrode distance causes greater current shunt- from this systematic review of rTMS and tDCS studies and
ing across the scalp and cerebral spinal fluid, resulting in meta-analysis of tDCS studies in ADHD was hampered by
only an estimated 35% of current reaching the brain.122 In heterogeneity in stimulation protocols, sample age and cog-
fact, it has been shown that bilateral electrode montage over nitive outcome measures. Larger, double-blind, randomized
the primary motor cortex can have neurologically neutral controlled trials with homogeneous protocols testing sys-
­effects.123 With regards to low power, only 2 studies65,66 had tematically for more optimal designs (e.g., multi-session
more than 30 participants; the sample size across all other stimulation combined with cognitive training, targeting
studies was relatively small, with an average of 14 partici- right dorsal and ventral frontal or inferior parietal re-
pants (with an n range of 7 to 20). Key outcome measures in gions),9,126 and testing both clinical and cognitive outcomes,
interference inhibition tasks such as the Stroop and flanker are needed to provide better insights into clinical and cogni-
reaction time or error interference effects (incongruent − tive effects, and to provide clear guidance on optimal stimu-
congruent reaction times/errors) were not reported; instead, lation protocols. Future studies should also be wary of over-
reaction times to incongruent trials were used to measure stating positive effects and account for possible cognitive
cognitive effects, meaning that effects on interference inhibi- costs of tDCS and rTMS in children.
tion measures were confounded by processing speed.64,67,68
Blinding integrity was not reported in 2 studies,43,64 failed in Acknowledgements: The authors thank Sophie Wallace Hanlon
3 studies65,67,71 and was potentially compromised in 3 studies, (S.W.H.) for assisting S.J.W. with the literature search and study
where at least 60% of participants correctly identified the identification. We also thank Zahra Soltaninejad43,64 for providing ad-
ditional and original data from her study for the meta-analysis, and
stimulation type;62,63,74 thus, placebo effects cannot be ex- for translating her paper into English.
cluded. The meta-analysis of tDCS studies was hampered by
the fact that only a minority of included studies controlled Affiliations: From the Department of Child & Adolescent Psychiatry,
Institute of Psychiatry, Psychology & Neuroscience, King’s College
for baseline differences by analyzing change scores (i.e., London, London, United Kingdom (Westwood, Rubia); the Institut
post-treatment minus baseline;62,65,66), while other studies an- d’Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain
alyzed only post-measurement scores to establish effects. (Radua); the Mental Health Research Networking Centre (CIBERSAM),
­Finally, the meta-regression analysis showed that studies Madrid, Spain (Radua); the Department of Clinical Neuroscience,
Centre for Psychiatric Research and Education, Karolinska Institutet,
with a high risk of “other” biases (e.g., no correction for mul-
Tomtebodavägen 18A, Stockholm, Sweden (Radua); and the Depart-
tiple testing, selective reporting of outcome measures or ment of Psychosis Studies, Institute of Psychiatry, Psychology and
­using a lenient significance threshold43,62–64,67,68) reported Neuro­science, King’s College London, De Crespigny Park, London,
larger effect sizes than studies with low or unclear risk of United Kingdom (Radua).

J Psychiatry Neurosci 2021;46(1) E29

Westwood et al.

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Funding: S. Westwood is supported by Action Medical Research tern of neural function in attention deficit hyperactivity disorder:
(GN2426), the Garfield Weston Foundation and the National Insti- a meta-analysis. Psychol Med 2014;44:869-80.
tute for Health Research (NIHR) Biomedical Research Centre at
   8. Hart H, Radua J, Mataix-Cols D, et al. Meta-analysis of fMRI stud-
South London and the Maudsley NHS Foundation Trust and King’s ies of timing in attention-deficit hyperactivity disorder (ADHD).
College London. K. Rubia receives research support from the Med­ Neurosci Biobehav Rev 2012;36:2248-56.
ical Research Council (MR/P012647/1) and the National Institute for
Health Research (NIHR) Biomedical Research Centre at South Lon-    9. Rubia K. Cognitive neuroscience of attention deficit hyperactivity
don and the Maudsley NHS Foundation Trust and King’s College disorder (ADHD) and its clinical translation. Front Hum Neurosci
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London. The views expressed are those of the author(s) and not
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PI14/00292 and PI19/00394 from the Plan Nacional de I+D+i 2013– and network meta-analysis. Lancet Psychiatry 2018;5:727-38.
2016 and and 2017–2020, the Instituto de Salud Carlos III-Subdirección 11. Swanson JM, Arnold LE, Jensen PS, et al. Long-term outcomes in
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all authors reviewed. All authors approved the final version to be logical and non-pharmacological treatment of attention deficit
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Content licence: This is an Open Access article distributed in ac-
cordance with the terms of the Creative Commons Attribution 13. Sonuga-Barke EJ, Brandeis D, Cortese S, et al. Nonpharmaco­
(CC BY-NC-ND 4.0) licence, which permits use, distribution and logical interventions for ADHD: systematic review and meta-­
analyses of randomized controlled trials of dietary and psycho­
reproduction in any medium, provided that the original publica-
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tion is properly cited, the use is non-commercial (i.e. research or
educational use), and no modifications or adaptations are made. 14. Cortese S, Ferrin M, Brandeis D, et al. Cognitive training for
See: https://creativecommons.org/licenses/by-nc-nd/4.0/ attention-deficit/hyperactivity disorder: meta-analysis of clinical
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