Medicines Q&As
Q&A 47.6
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: 12th June 2013
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, including the UK, although higher prevalences have been
reported in The Netherlands (5%) and France (7.3%). (1-4) Adult ADHD is widely under-recognised.
(1, 5) 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) It is suggested that ADHD
in childhood can persist into adulthood in at least 30% of patients. (6) 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) ADHD has been diagnosed
for the first time in adults aged 55-70 years. (7)
A clinical guideline on the diagnosis and management of ADHD in children, young people and adults
was issued 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. If methylphenidate is ineffective or
unacceptable, atomoxetine or dexamfetamine can be tried. (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. (8, 9)
The methylphenidate preparations currently available in the UK are not licensed for use in adults (813). However, methylphenidate hydrochloride is licensed for use in adults in America. (14)
Atomoxetine is licensed for use in adults with ADHD in the UK. The presence of pre-existing
symptoms in childhood should be confirmed. (15)
Available through NICE Evidence Search at www.evidence.nhs.uk
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Medicines Q&As
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. (16) 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
with placebo. (16) Only one RCT (17) 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. (16)
Table 1 - Efficacy results from double blind, placebo controlled studies in adults with ADHD
Ref
no.
17
18
19
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 (17) and Spencer et al (18) studies concluded that once daily doses of
SR methylphenidate had similar efficacy to three times daily doses of IR methylphenidate. (20)
Since the NICE clinical guideline publication, a number of papers have reviewed and assessed the
efficacy, tolerability and long term use of immediate release and sustained release methylphenidate in
adults with ADHD. The studies demonstrate efficacy for both methylphenidate formulations and
indicate that use of methylphenidate results in statistically significant improvement of ADHD
symptoms according to various rating scales. (21-28) A meta-regression analysis of the efficacy of
methylphenidate for adults with ADHD showed an improvement in symptoms in a dose dependent
Available through NICE Evidence Search at www.evidence.nhs.uk
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Medicines Q&As
fashion. The efficacy of methylphenidate appears to be reduced in patients with comorbid substance
use disorders. It is unclear if methylphenidate efficacy is influenced by type of formulation. (29)
The studies included in the NICE clinical guideline were only 6 weeks duration, other studies have
been conducted from 24 weeks to more than 4 years. (21-27) A naturalistic follow up study showed
that treatment of ADHD in adults for more than 2 years was associated with better functioning than
treatment for 2 years or less. Comorbidity at baseline predicted poorer outcome. (26)
All the studies showed quite high rates of discontinuation of methylphenidate, some over 50%. In
many cases, discontinuation was due to adverse effects or lack of efficacy due to the low doses used
in the studies. (21-27) There is a positive correlation between dropout rate and the dose of
methylphenidate. (28) Post-hoc analysis of a randomised, double blind, placebo controlled trial with
SR methylphenidate 54mg and 72mg suggest that women, newly diagnosed patients, patients with a
substance use disorder and subjects with high educational degrees seem to have a higher risk of
non-adherence and therefore a reduction in improvement in symptoms. (30)
Cardiovascular adverse effects have been noted in the clinical trials, for example, a mean increase in
pulse rate of 4.8 beats per minute (21, 28), increased heart rate (23, 25), mean increases of
2.8mmHg and 2.7mmHg for systolic and diastolic blood pressure (25, 28) and tachycardia (25). A
retrospective, population based cohort study in adults with ADHD aged 25-64 years showed that
current or new use of ADHD medications, including methylphenidate, was not associated with an
increased risk of serious cardiovascular events such as myocardial infarction, sudden cardiac death
and stroke. (31, 32) A non-randomised cohort study focussing specifically on methylphenidate and
serious cardiovascular events in adults concluded that although initiation of methylphenidate was
associated with a 1.8 fold increase in risk of sudden death or ventricular arrhythmia, there is a lack of
dose response which suggests the association may not be causal. (33)
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.
Improvement in symptoms is dose dependent and sustained release and immediate release
methylphenidate preparations have similar efficacy in adults.
A naturalistic follow up study showed that treatment of ADHD in adults for more than 2 years was
associated with better functioning than treatment for 2 years or less. Co-morbidity at baseline is a
predicter of poorer outcome.
There is a positive correlation between dropout rate and the dose of methylphenidate. Women,
newly diagnosed patients, patients with a substance use disorder and subjects with high
educational degrees seem to have a higher risk of non-adherence.
Large cohort studies have shown that current or new use of ADHD medications, including
methylphenidate, is not associated with an increased risk of serious cardiovascular events such
as myocardial infarction, sudden cardiac death and stroke. Initiation of methylphenidate is
associated with a 1.8 fold increase in risk of sudden death or ventricular arrhythmia, although
there is a lack of dose response which suggests the association may not be causal.
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)
Available through NICE Evidence Search at www.evidence.nhs.uk
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Medicines Q&As
References
1. NICE Clinical Guideline 72. Attention deficit hyperactivity disorder: diagnosis and management of
ADHD in children, young people and adults. Issued September 2008, last modified March 2013.
Accessed via http://www.nice.org.uk on 29/05/13.
2. Bazire S. Psychotropic Drug Directory 2012. HealthComm UK Ltd. 2012 p34-37
3. McCarthy S, Wilton L et al. The epidemiology of pharmacologically treated attention deficit
hyperactivity disorder (ADHD) in children, adolescents and adults in UK primary care. BMC
Paediatrics 2012; 12: 78 http://www.biomedcentral.com/1471-2431/12/78
4. Brod M, Pohlman B et al. Comparison of the burden of illness for adults with ADHD across seven
countries: a qualitative study. Health and Quality of Life Outcomes 2012; 10: 47
http://www.hqlo.com/content/10/1/47
5. Anon. Adults with ADHD: ignored and under-treated. Drug and Therapeutics Bulletin 2011; 49 (7):
73
6. Post RE, Kurlansik SL. Diagnosis and management of Attention-Deficit/Hyperactivity Disorder in
adults. American Family Physician 2012; 85 (9): 890-6
7. Manor I; Rozen S; et al. When does it end? Attention-deficit/hyperactivity disorder in the middle
aged and older populations. Clinical Neuropharmacology 2011; 34 (4): 148-54.
8. Summary of Product Characteristics - Concerta XL 18mg-36mg prolonged-release tablets.
Janssen-Cilag Ltd. Accessed via http://emc.medicines.org.uk on 29/05/13 [last revised 18/02/13].
9. Summary of Product Characteristics - Concerta XL 27mg prolonged-release tablets. JanssenCilag Ltd. Accessed via http://emc.medicines.org.uk on 29/05/13 [last revised 18/02/13].
10. Summary of Product Characteristics - Equasym XL 10mg, 20mg & 30mg capsules. Shire
Pharmaceuticals Ltd. Accessed via http://emc.medicines.org.uk on 29/05/13 [last revised
11/10/11].
11. Summary of Product Characteristics - Ritalin tablets. Novartis Pharmaceuticals UK Ltd. Accessed
via http://emc.medicines.org.uk on 29/05/13 [last revised 13 June 2011].
12. Summary of Product Characteristics - Medikinet tablets. Flynn Pharma Ltd. Accessed via
http://emc.medicines.org.uk on 29/05/13 [last revised 21/12/11].
13. Summary of Product Characteristics - Medikinet XL prolonged-release capsules. Flynn Pharma
Ltd. Accessed via http://emc.medicines.org.uk on 29/05/13 [last revised 21/12/11].
14. DRUGDEX® Drug Evaluation – methylphenidate. DRUGDEX electronic version, Thomson
Micromedex, USA. Accessed via http://www.thomsonhc.com on 07/06/13.
15. Summary of Product Characteristics – Strattera 10mg, 18mg, 25mg, 40mg, 60mg, 80mg or
100mg hard capsules. Eli Lilly and Company Ltd. Accessed via http://emc.medicines.org.uk on
02/07/13 [last revised 28/05/13].
16. 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 07/06/13.
17. Biederman J, Mick E et al. A randomised, placebo-controlled trial of OROS methylphenidate in
adults with attention-deficit/hyperactivity disorder. Biological Psychiatry 2006; 59: 829-35.
18. 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.
19. 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.
20. 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.
21. 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.
22. 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 (5): 549-53.
23. 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.
Available through NICE Evidence Search at www.evidence.nhs.uk
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Medicines Q&As
24. Wender PH, Reimherr FW et al. A one year trial of methylphenidate in the treatment of ADHD.
Journal of Attention Disorders 2011; 15 (1): 36-45.
25. 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.
26. Lensing MB, Zeiner P et al. Four year outcome in psychopharmacologically treated adults with
attention-deficit/hyperactivity disorder: a questionnaire survey. Journal of Clinical Psychiatry 2013;
74 (1): e87-93
27. Buitelaar JK, Trott G-E et al. Long term efficacy and safety outcomes with OROS-MPH in adults
with ADHD. International Journal of Neuropsychopharmacology 2012; 15: 1-13.
28. Santosh PJ, Sattar S et al. Efficacy and tolerability of pharmacotherapies for attention-deficit
hyperactivity disorder in adults. CNS Drugs 2011; 25 (9): 737-63
29. Castells X, Ramos-Quiroga JA et al. Efficacy of methylphenidate for adults with attention-deficit
hyperactivity disorder. A meta-regression analysis. CNS Drugs 2011; 25 (2): 157-69
30. Kooji JJS, Rosler M et al. Predictors and impact of non-adherence in adults with attentiondeficit/hyperactivity disorder receiving OROS methylphenidate: results from a randomized,
placebo-controlled trial. BMC Psychiatry 2013;13:36
http://www.biomedcentral.com/1471-244X/13/36
31. Habel LA, Cooper WO et al. ADHD medications and risk of serious coronary heart disease in
young and middle-aged adults. Effective Health Care Program Research Reports, no. 36,
December 2011.
32. Habel LA, Cooper WO et al. ADHD medications and risk of serious coronary heart disease in
young and middle-aged adults. Journal of the American Medical Association 2011; 306 (24):
2673-83
33. Schelleman H, Bilker WB et al. Methylphenidate and risk of serious cardiovascular events in
adults. American Journal of Psychiatry 2012; 169: 178-85
Quality Assurance
Prepared by
Katie Smith, East Anglia Medicines Information Service
Date Prepared
12th June 2013 (partial update 2 July 2013)
Checked by
Sarah Cavanagh, East Anglia Medicines Information Service
Date of check
25th June 2013 (partial update 2 July 2013)
Search strategy

Embase: [[ATTENTION DEFICIT DISORDER/ AND ADULT/] AND METHYLPHENIDATE] [Limit
to: Publication Year 2011-2013 and Human and (Human Age Groups Adult 18 to 64 years) and
English Language and (Clinical Trials Clinical Trial)]
 Medline: [ATTENTION DEFICIT DISORDER WITH HYPERACTIVITY/ AND ADULT/] AND
METHYLPHENIDATE/ [Limit to: Publication Year 20011-2013 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
 NICE Evidence: 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: 2011-2013
Available through NICE Evidence Search at www.evidence.nhs.uk
5