Medicines Q&As
Q&A 47.4
Can methylphenidate be used for adults with attention deficit
hyperactivity disorder (ADHD)?
Prepared by UK Medicines Information (UKMi) pharmacists for NHS healthcare professionals
Before using this Q&A, read the disclaimer at www.ukmi.nhs.uk/activities/medicinesQAs/default.asp
Date prepared: 28th June 2011
Background
ADHD is a behavioural syndrome characterised by the core symptoms of hyperactivity, impulsivity
and inattention. Symptoms of ADHD can overlap with symptoms of other related disorders, in adults
they include personality disorders, bipolar disorder, obsessive compulsive disorder and substance
misuse. (1) ADHD is thought to affect about 3–9% of school-age children and young people in the UK,
and about 2-4% of adults worldwide. (1, 2) Adult ADHD is widely under-recognised. Adults may
receive a first diagnosis of ADHD having never been diagnosed as a child but have a history of
symptoms, or have late onset ADHD which is considered controversial and relatively rare. (2) Most
young people with a diagnosis of ADHD will go on to have significant difficulties in adulthood, which
may include continuing ADHD, personality disorders, emotional and social difficulties, substance
misuse, unemployment and involvement in crime. (1)
A clinical guideline on the diagnosis and management of ADHD in children, young people and adults
was published by the National Institute for Health and Clinical Excellence (NICE) in September 2008.
(1) It states that people with ADHD require integrated care that addresses a wide range of personal,
social, educational and occupational needs. Care should be provided by adequately trained
healthcare and education professionals.
Adults presenting with symptoms of ADHD who do not have a childhood diagnosis should be referred
for assessment by a mental health specialist trained in the diagnosis and management of ADHD.
Adults who have previously been treated for ADHD as children or young people and have symptoms
suggestive of continuing ADHD should be referred to adult psychiatric services for assessment. Drug
treatment for adults with ADHD should always form part of a comprehensive treatment programme
that addresses psychological, behavioural and educational or occupational needs. Drug treatment is
first line treatment for adults with ADHD with either moderate or severe levels of psychological, social
and/or educational or occupational impairment. (1)
Answer
The NICE clinical guideline states that following a decision to start drug treatment in adults with
ADHD, methylphenidate should normally be tried first. (1) There is currently only one methylphenidate
preparation available in the UK which has information on administration to adults in its summary of
product characteristics (SPC). Concerta XL can be used in adolescents whose symptoms persist into
adulthood and who have shown clear benefit from treatment, so it may be appropriate to continue
treatment into adulthood. However, starting treatment with Concerta XL in adults is not appropriate.
Safety and efficacy have not been established for the initiation of treatment in adults or the routine
continuation of treatment beyond 18 years of age. If treatment withdrawal has not been successful
when an adolescent has reached 18 years of age continued treatment into adulthood may be
necessary. The need for further treatment of these adults should be reviewed regularly and
undertaken annually. (3, 4)
The methylphenidate preparations currently available in the UK are not licensed for use in adults (59). However, methylphenidate hydrochloride is licensed for use in adults in America. (10)
The NICE guideline development group (GDG) identified a number of studies published between
1976 and 2007 that assessed the efficacy and safety of pharmacological treatments for ADHD.
However, a large majority were excluded as they lacked validated outcome measures. (11) The use
of methylphenidate in adults is based on the results of 3 studies – see table 1. The NICE GDG
summarised that in adults with ADHD, high dose methylphenidate showed evidence of a reduction in
ADHD symptoms as rated by an investigator but a small effect of improvement in medium doses as
measured from self-reports. There was also evidence of global clinical improvement when compared
From the NHS Evidence website www.evidence.nhs.uk
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Medicines Q&As
with placebo. (11) Only one RCT (12) assessed side effects and indicated that high dose
methylphenidate is more likely than placebo to cause particular side effects: decreased appetite,
gastrointestinal problems, tension, cardiovascular complaints, depression, dizziness, anxiety,
autonomic symptoms, increased energy, tics, skin problems, bruising and sexual problems.
Methylphenidate may reduce the risk of discontinuation when compared with placebo. Long-term
studies of side effects in adults are scarce. Safety reviews have indicated an association between the
use of methylphenidate and sudden death, however, given the lack of background rates the evidence
is inconclusive. The GDG concluded that methylphenidate is effective in reducing ADHD core
symptoms and in producing clinical improvement as rated by investigators in adults with ADHD and
high dose methylphenidate may increase side effects. (11)
Table 1 - Efficacy results from double blind, placebo controlled studies in adults with ADHD
Ref
no.
12
13
14
Study details
Methylphenidate
preparation
36mg SR tablet
[osmotic release
oral system]
Mean daily
dose
80.9  31.8mg
146 adults
R, DB, PC, PD
6 weeks
duration
5mg & 10mg IR
capsules
82 ± 22mg
45 adults
R, DB, PC, CO
6 weeks
duration
10mg IR tablets
149 adults
R, DB, PC
6 weeks
duration
(0.99 ± 0.32
mg/kg)
(1.1 ± 0.24
mg/kg)
Mean total daily
dose not stated
(0.91mg/kg,
range 0.541.04 mg/kg)
Results at study endpoint
66% methylphenidate vs. 39%
placebo subjects reported much
or very much improved on the
CGI Improvement scale and a
>30% reduction in ADHD
symptoms on AISRS (p<0.001).
68% methylphenidate vs. 17%
placebo subjects reported much
or very much improved on the
CGI Improvement scale and a
>30% reduction in ADHD
symptoms on AISRS (p<0.0001).
38% methylphenidate vs. 7%
placebo subjects had a decrease
of at least 2 points on the CGIADHD and a >30% symptom
reduction measured by the DSMIV ADHD rating scale (p=0.003).
Key: R = randomised, DB = double blind, PC = placebo controlled, CO = cross over, PD = parallel
design, SR = sustained release, IR = immediate release, CGI-ADHD = Clinical Global Impression
scale for ADHD (investigator assessment), AISRS = Adult ADHD Investigator System Report Scale,
DSM-IV ADHD = Diagnostic and Statistical Manual of Mental Disorders 4th edition ADHD rating scale
(patient self assessment)
A comparison of the acute efficacy and tolerability of the 2 different methylphenidate preparations
used in the Biederman et al (12) and Spencer et al (13) studies concluded that once daily doses of
SR methylphenidate had similar efficacy to three times daily doses of IR methylphenidate. (15)
A systematic review and indirect comparison meta-analysis of the comparative benefits and harms of
medicines for adults with ADHD concluded that the current best evidence supports using immediate
release methylphenidate as first line treatment for most adults with ADHD. (16)
Recently more trials have been published which have looked at the long term use and safety of
methylphenidate in adults with ADHD. A summary is available in table 2.
Table 2 - Efficacy and safety results from long term studies in adults with ADHD
Ref
no.
17
Study details
359 adults
R, PC
24 weeks
duration
Methylphenidate
preparation
10mg ER tablet
Mean daily
dose
41.2  18.2mg
(0.55 ± 0.27
mg/kg)
Results at study endpoint
61% methylphenidate vs. 42%
placebo subjects reported a
>30% reduction in WRAADDS
score, p=0.001.
From the NHS Evidence website www.evidence.nhs.uk
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Medicines Q&As
18
19
20
21
227 adults
R, DB, PC, PD
34 weeks
duration – 3
phases (see
below)
133 adults
Prospective
study
2 year duration
78 adults
OL
24-52 weeks
duration
36mg SR tablet
[osmotic release
oral system]
78.4 ± 31.7mg
IR and SR tablets
48.9 ± 21.0mg
10mg IR tablets
60 ± 24mg
550 adults
OL, NR, DT
6 or 12 months
duration
36mg SR tablet
[osmotic release
oral system]
67.4 ± 24.09mg
(0.97 ± 0.32
mg/kg)
62% methylphenidate vs. 37%
placebo subjects reported much
or very much improved on the
CGI Improvement scale and a
>30% reduction in ADHD
symptoms on AISRS (p<0.0001).
Adults given methylphenidate
(65%) or dexamphetamine (35%).
After 2 years, 50% of patients still
adhered to treatment.
At the end of 12 months,
symptom severity decreased by
80% from baseline, WSAS
decreased >50% in all subscales,
and the average GAF improved
significantly, p<0.0001.
Following titration to a dose
where subjects reported much or
very much improved on the CGI
Improvement scale and a >30%
reduction in ADHD symptoms on
AISRS, the response was
maintained during the 6 or 12
month open label period.
Key: ER = extended release, WRAADDS = Wender-Reimherr adult attention deficit disorder scale, OL
= open label, WSAS = Weissman Social Adjustment Scale, GAF = global assessment of functioning,
NR = nonrandomized, DT = dose titration
The 24 week study was conducted in Germany. A total of 110 adults discontinued the study
prematurely. The main reasons were lack of efficacy in the placebo group and adverse events in the
methylphenidate group. Methylphenidate statistically significantly increased pulse rate (72 beats per
minute (bpm) at baseline, 77 bpm at week 4, p<0.0001) but not heart rate or blood pressure. The
authors concluded that the interpretation of the results is limited by the low dose-range used in this
study, a high drop-out rate (30%) and a placebo response which might have affected the therapeutic
effect size. (17)
The 34 week study consisted of 3 phases: phase 1 - a 6 week, double blind, randomised, placebo
controlled, parallel design study followed by phase 2 - a 24 week double blind, maintenance study for
responders in phase 1 and finally phase 3 - a 4 week double blind, placebo controlled, discontinuation
study. The efficacy results are from phase 1. At all phases, discontinuations from methylphenidate
were due to adverse effects and discontinuations from placebo were due to lack of efficacy. Twenty
three (10%) subjects were randomised for phase 3. Methylphenidate was associated with a higher
incidence of anorexia, dry mouth, moodiness, anxiety, insomnia, subjective cardiovascular complaints
and dizziness. The study recommends adults with ADHD, particularly those with borderline
hypertension, should be monitored for changes in blood pressure and weight loss. (18)
The 2 year study was conducted in Sweden and showed that improvements in attention problems,
impulsivity, restlessness and irritability 6-9 months after treatment initiation, predicted adherence to
treatment at 2 years. Approximately 17% of subjects discontinued due to adverse effects and 15%
due to lack of efficacy although this may be due to the low doses used in the study. Elevated heart
rate occurred early in treatment and was maintained at the 2 year time point. (19)
Following a 4 week randomised, double blind, placebo controlled, cross over trial in 116 adults of
methylphenidate and placebo, 78 who experienced at least 50% decrease in WRAADS on
methylphenidate entered a 6 to 12 month, open label trial. 64 adults completed 6 months and 57
completed 12 months. The improvements in ADHD symptoms in the double blind phase were
continued during the open label phase. There was a statistically significant drop in body weight
From the NHS Evidence website www.evidence.nhs.uk
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Medicines Q&As
between baseline and study end (at 6 months - women 12.5 pounds, men 9.8 pounds, p=0.001; at 12
months, women 10.8 pounds, men 10.8 pounds, p=0.005). (20)
All subjects in the dose titration study had up to 5 weeks to titrate the dose of methylphenidate to
achieve a certain level of response before entering the observation period for 6 or 12 months. 73.5%
of adults were classified as responders by the end of the titration period. 258 adults entered the 6
month trial and 292 adults entered the 12 month trial. Overall 43.4% of adults withdrew from the 6
month study and 55.8% from the 12 month study. An adverse effect was the reason for withdrawal in
100 (18.2%) adults, 65 in the 12 month study and 35 in the 6 month study. Adverse effects also lead
to a dose reduction in 30.4% adults. Greater than 5% of adults reported increased heart rate,
increased blood pressure and tachycardia. The authors noted that the changes were modest, not
thought to be clinically meaningful and consistent with known effects of stimulant medications. (21)
Summary








NICE clinical guidelines on the diagnosis and management of ADHD in children, young people
and adults state that following a decision to start drug treatment in adults with ADHD,
methylphenidate should normally be tried first.
Methylphenidate preparations currently available in the UK are not licensed for use in adults.
The SPC for Concerta XL says it can be used in adolescents whose symptoms persist into
adulthood and who have shown clear benefit from treatment, so it may be appropriate to continue
treatment into adulthood. However, starting treatment with Concerta XL in adults is not
appropriate.
Methylphenidate is effective in reducing ADHD core symptoms and in producing clinical
improvement in adults with ADHD when assessed against investigator rating scales.
High dose methylphenidate is more likely than placebo to cause side effects such as decreased
appetite, gastrointestinal problems, tension, cardiovascular complaints, depression, dizziness,
anxiety, autonomic symptoms, increased energy, tics, skin problems, bruising and sexual
problems.
Adults with ADHD, particularly those with borderline hypertension, should be monitored for
changes in blood pressure and weight loss.
Sustained release and immediate release methylphenidate preparations have similar efficacy in
adults.
Further data on the long term safety and efficacy of methylphenidate use in adults is needed.
Limitations
This question has only examined the use of methylphenidate for treatment of adults with ADHD. Other
stimulants have also been studied e.g. dexamphetamine, atomoxetine. Non-stimulants that may
provide a response include bupropion, monoamine oxidase inhibitors, lithium and venlafaxine. (2)
References
1. NICE Clinical Guideline 72. Attention deficit hyperactivity disorder. September 2008. Accessed via
http://www.nice.org.uk on 10/06/11.
2. Bazire S. Psychotropic Drug Directory 2010. HealthComm UK Ltd. 2010 p27-33
3. Summary of Product Characteristics - Concerta XL 18mg-36mg prolonged-release tablets.
Janssen-Cilag Ltd. Accessed via http://emc.medicines.org.uk on 12/07/11 [last revised 22 June
2011].
4. Summary of Product Characteristics - Concerta XL 27mg prolonged-release tablets. JanssenCilag Ltd. Accessed via http://emc.medicines.org.uk on 10/06/11 [last revised 22 June 2011].
5. Summary of Product Characteristics - Equasym 5mg, 10mg & 20mg tablets. Shire
Pharmaceuticals Ltd. Accessed via http://emc.medicines.org.uk on 10/06/11 [last revised 9 June
2010].
6. Summary of Product Characteristics - Equasym XL 10mg, 20mg & 30mg capsules. Shire
Pharmaceuticals Ltd. Accessed via http://emc.medicines.org.uk on 10/06/11 [last revised 26 May
2011].
7. Summary of Product Characteristics - Ritalin tablets. Novartis Pharmaceuticals UK Ltd. Accessed
via http://emc.medicines.org.uk on 10/06/11 [last revised 5 February 2010].
From the NHS Evidence website www.evidence.nhs.uk
4
Medicines Q&As
8. Summary of Product Characteristics - Medikinet tablets. Flynn Pharma Ltd. Accessed via
http://emc.medicines.org.uk on 10/06/11 [last revised 24 June 2010].
9. Summary of Product Characteristics - Medikinet XL prolonged-release capsules. Flynn Pharma
Ltd. Accessed via http://emc.medicines.org.uk on 10/06/11 [last revised 10 January 2011]
10. DRUGDEX® Drug Evaluation – methylphenidate. DRUGDEX electronic version, Thomson
Micromedex, USA. Accessed via http://www.thomsonhc.com on 10/06/11.
11. National Collaborating Centre for Mental Health. ADHD. Diagnosis and management of ADHD in
children, young people and adults. The British Psychological Society and The Royal College of
Psychiatrists, 2009. Accessed via http://www.nice.org.uk on 10/06/11.
12. Biederman J, Mick E et al. A randomised, placebo-controlled trial of OROS methylphenidate in
adults with attention-deficit/hyperactivity disorder. Biol Psychiatry 2006; 59: 829-35.
13. Spencer T, Biederman J et al. A large, double-blind, randomised clinical trial of methylphenidate
in the treatment of adults with attention-deficit/hyperactivity disorder. Biological Psychiatry 2005;
57: 456-63.
14. Kooij JJS, Burger H et al. Efficacy and safety of methylphenidate in 45 adults with attentiondeficit/hyperactivity disorder. A randomised placebo-controlled double-blind cross-over trial.
Psychological Medicine 2004; 34: 973-82.
15. Biederman J, Mick EO et al. Comparative acute efficacy and tolerability of OROS and immediate
release formulations of methylphenidate in the treatment of adults with attentiondeficit/hyperactivity disorder. BMC Psychiatry 2007; 7: 49.
16. Peterson K, McDonagh MS et al. Comparative benefits and harms of competing medications for
adults with attention-deficit hyperactivity disorder: a systematic review and indirect comparison
meta-analysis. Psychopharmacology 2008; 197: 1-11.
17. Rosler M, Fischer R et al. A randomised, placebo-controlled, 24 week study of low dose
extended-release methylphenidate in adults with attention-deficit/hyperactivity disorder. European
Archives of Psychiatry and Clinical Neuroscience 2009; 259 (2): 120-9.
18. Biederman J, Mick E et al. A randomized, 3-phase, 34-week, double blind, long term efficacy
study of osmotic-release oral system-methylphenidate in adults with attention-deficit/hyperactivity
disorder. Journal of Clinical Psychopharmacology 2010; 30: 549-53.
19. Bejerot S, Ryden E et al. Two-year outcome of treatment with central stimulant medication in
adult attention-deficit/hyperactivity disorder: a prospective study. Journal of Clinical Psychiatry
2010; 71 (12): 1590-7.
20. Wender PH, Reimherr FW et al. A one year trial of methylpenidate in the treatment of ADHD.
Journal of Attention Disorders 2011; 15 (1): 36-45.
21. Adler LA, Orman C et al. Long-term safety of OROS methylphenidate in adults with attentiondeficit/hyperactivity disorder. An open-label, dose-titration, 1 year study. Journal of Clinical
Psychopharmacology 2011; 31: 108-114.
Quality Assurance
Prepared by
Katie Smith, East Anglia Medicines Information Service
Date Prepared
28th June 2011 (date or partial revision 12 July 2011)
Checked by
Sarah Cavanagh, East Anglia Medicines Information Service
Date of check
4th July 2011 (partial revision checked xx July 2011)
Search strategy

Embase: [[ATTENTION DEFICIT DISORDER/ AND ADULT/] AND METHYLPHENIDATE] [Limit
to: Publication Year 2009-2011 and Human and (Human Age Groups Adult 18 to 64 years) and
English Language and (Clinical Trials Clinical Trial)]
From the NHS Evidence website www.evidence.nhs.uk
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Medicines Q&As

Medline: [ATTENTION DEFICIT DISORDER WITH HYPERACTIVITY/ AND ADULT/] AND
METHYLPHENIDATE/ [Limit to: Publication Year 2009-2011 and (Publication Types Clinical Trial,
All) and Humans and (Age Groups All Adult 19 plus years) and English Language]
 In-house database/resources: search terms = methylphenidate, hyperkinetic syndrome, adult
 Electronic Medicines Compendium: search term = methylphenidate, adults, ADHD
 National Electronic Library for Medicines: search terms = methylphenidate + adult + hyperkinetic
syndrome
 DrugDex methylphenidate drug evaluation: ADHD, adults
 IDIS: "METHYLPHENIDATE 28200009" and "SYN-HYPERKINETIC, CHILDHOOD 314." and
"CASE REPORT ADULT 0" or "STUDY ADULT 3" or "REVIEW ADULT 6" or "REPORT ADULT
7" or "STUDY RANDOMIZE ADULT 135" or "STUDY COHORT ADULT 138" or "STUDY CASECONT ADULT 141" Years: 2009-2011
From the NHS Evidence website www.evidence.nhs.uk
6