I prepared this presentation to give primary care physicians (general practitioners) updates on treatment of adult ADHD. It is a summary of relevant European and UK guidleins. The presentation will be uploaded to GP Lectures website: http://www.gplectures.co.uk/

2. By the end of this presentation
you should know more about..
• Evidence base
• Drugs used in Adult ADHD and their side effects
• Shared care protocols
• How to monitor treatment and when to refer back to
specialist

3. Recommend reading
NICE guidelines for treatment of ADHD [CG72] (2008-
updated 2013)
Summary of the guidelines for the pharmacological
management of ADHD recommendations from the British
Association for Psychopharmacology (Bolea-Alamañac at
al, 2014)
European consensus statement on diagnosis and
treatment of adult ADHD: The European Network Adult
ADHD (Kooij et al, 2010)

4. Two important neurotransmitters:
(dopamine, noradrenaline)
Responsible for most functional impairment in
ADHD
There is impairment in neurotransmitters' function
and 70% of patients report improvement with
medication
The improvement is dramatic
Side effects are transient and not severe (usually)

5. Neurobiological dysfunction in ADHD
This has been demonstrated by numerous
literature and brain imaging studies
The most effective treatment is to target this
neurotransmitters dysfunction
Unless this is done, other interventions may not
be so effective

6. Substance Misuse in ADHD
The prevalence is higher in adults with ADHD
The onset is typically earlier, last longer, and
slow to remit (compared to non ADHD adults)
Early treatment reduce risk of drug abuse in
future (results of meta-analysis review by
Wilens et al, 2003 and case control study by
Wilens et al, 2008)

7. ADHD in older people
ADHD is not “outgrown” in older persons
The prevalence is similar across all ages (3-5%)
There are 15 case studies of older patients (67-81 yrs)
successfully treated with stimulant medication
Close monitoring of physical health (especially
cardiovascular side effects) during treatment
( Michielsen et al, 2012, Das et al, 2014)

8. Aims of Drug Treatment
To treat the core symptoms:
Inattentive ± hyperactive, impulsive
To treat the associated impairment:
Educational, learning problems, problems due to poor
performance at work (clumsiness, attention problems)
To treat comorbidities:
Mood and anxiety treatment has better outcome if ADHD is
treated. Combined treatment (for ADHD and for the
comorbidity) is the rule rather than the exception

9. Impact of non-treatment
Higher rates of academic failure
Low occupational status
Increased risk of substance use disorders (tobacco,
alcohol or drugs)
Accidents and delinquency
Fewer social relationships or friends

10. Controversial Treatments for
ADHD
Dietary modification (avoiding artificial additives,
sugars, etc...)
Dietary supplements: vitamins or anti-oxidants,
algae, omega 3.
No established evidence for the effectives and
safety of these treatments.

11. Treatment priorities in ADHD
First treat most severe disorder, usually affective
disorders, substance misuse, then treat ADHD
In case of personality disorder: first treat ADHD
Treatment of milder depressive and anxiety
disorders may be delayed and re-assessed after
ADHD treatment (may improve significantly)

12. Types of non-pharmacological
treatments
Psycho-education very important component of
treatment.
Cognitive-behavioral treatment: to improve self-
confidence, self esteem
Coaching
Others: Meta-cognitive therapy (MCT), Cognitive
remediation programs (CRP) and Mindfulness
based therapies

13. Medications for ADHD
Are safe and effective but need specialist input
The doses for adults can be more difficult to determine,
as most studies were done on children
Require gradual titration and monitoring to “fine tune”
according to the individual needs and daily life activities
Drug treatments for adults with ADHD should always
form part of a comprehensive treatment (NICE)

14. Prevalence of treatment in the adult
in UK
Less than 10% of adults with ADHD requiring medication
are thought to receive treatment
High discontinuation rate during transition from adolescents
to adulthood (16-18 years) (McCarthy et al., 2009).
In contrast to children ADHD treatment, NICE recommends
that pharmacological interventions are always first line in
adults (NICE, 2008).

15. Patients’ Concerns Regarding
Medications
 My change my personality, dull, become like a “zombie”?
 I will become a “junkie”, or people will think I am one
 Effect on growth
 Induce tics (or make them worse)
 Effect on sleep, appetite, sex
 I need to use it all my life

16. Licensed indications
Currently only atomoxetine is licensed for treatment of
adults with ADHD provided that it was started before
the age of 18.
The prescription of atomoxetine for the first time after
the age of 18 and the prescription of stimulants is “off-
label”.
But stimulant medications are supported by NICE,
BAP & European guidance and the BNF.

17. Summary of NICE Guidelines
Medication is the first-line treatment in adults
Methylphenidate is the first-line drug
If methylphenidate is ineffective or unacceptable then
atomoxetine or dexamphetamine can be tried 2nd line
In the following situations:
1. Residual symptoms
2. Poor or no response
3. Medication is not an option
4. The patient refuses medication
........then consider CBT

18. Controlled Drugs
Methylphenidate and dexamfetamine are schedule 2
controlled drugs (CD) thus are subject to prescription
requirements.
Hence prescriptions must states the form and strength
of preparation (e.g. 10mg tablets); the dose (e.g. 10mg
TDS) and total quantity or number of dose units in
words AND figures (e.g. 500 mg = Five Hundred
milligrams).
A prescription can be given for a maximum of 28 days.

19. Classes of Medication
Stimulants
 Methylphenidate
 Amphetamine compounds
 Dextroamphetamine
 Lisdexamfetamine
Non-stimulant
 Atomoxetine
Antidepressants
 Tricyclics
 Bupropion

20. Antihypertensives
 Clonidine
 Guanfacine
Miscellaneous
 Combined pharmacotherapy
 Modafinil
 Venlafaxine
 Neuroleptics (only in severe cases with monitoring)

21. Stimulants
 Have been used for decades (treatment of ADHD since
1960s)
 Available in prolonged release formulations
(recommended)
 Use is supported by more than 250 randomised controlled
studies over 40 years
 They enhance dopamine levels by blocking pre-synaptic
dopamine transporter
 Almost immediate effects is noticed with short acting
formulation (within 20 minutes)
(Faraone et al 2003, Volkow et al 2002, Pietrzak at el 2006)

22. Advantages of Extended-Release
Formulations of Stimulants
They provide prolonged and sustained level of
medication spread throughout the day
The onset of the action and end is smoother, which
reduces the symptoms fluctuations during the day
May fit better around school, work commitments
Better compliance, less doses
May reduce diversion and abuse

23. Substance misuse and medication
Not widely reported in the UK.
To provide a sensation of “high”, the stimulant (short acting)
should be injected or snorted.
The risks of abuse can therefore be largely avoided by use
of long-acting formulations of stimulants.
The prodrug lisdexamfetamine is the first pro-drug licensed
in Europe for ADHD and has a very low abuse potential and
is a good alternative to immediate-release dexamfetamine.

24. Management of some of the
common side effects
Appetite loss
Monitor weight before and after treatment
regularly
Take the medication with or after meals
Eat regularly
Use medication holidays

25. Insomnia
Explore pre-treatment sleep pattern (ADHD is
commonly associated with delayed sleep onset
and insomnia)
Advice about sleep hygiene
Reduce the dose, or switch to shorter acting
stimulant
Consider adjunctive medication (e.g., melatonin,
clonidine)

26. Irritability
Assess onset (when the drug level peaks:
too high dose, or when the drugs wears off:
rebound symptoms)
Review the dose
Assess for comorbidity (is irritability part of
anxiety/mood symptoms)
Consider combined treatment

27. Methylphenidate
 Methylphenidate hydrochloride (5, 10, 20) including
Medikinet®
 Duration of action: 3-4 hours
 Dose: 5 mg 2–3 times daily increased if necessary at weekly
intervals according to response, max. 100 mg daily in 2–3
divided doses
 Evening dose If effect wears off in evening (with rebound
hyperactivity) a dose at bedtime may be appropriate
(establish need with trial bedtime dose)

28. Concerta® XL tablet (Janssen)
 Schedule 2 controlled drug
 22% immediate-release component, 78% modified-release
 Dose: 18 mg, 27 mg, 36 mg.
 Initially 18 mg once daily in the morning, adjusted at weekly
intervals according to response, max. 108 mg daily
 15 mg of standard-release methylphenidate is equivalent to 18
mg Concerta® XL 18 mg once daily

29. Equasym XL® capsules (Shire)
 Schedule 2 controlled drug
 10 mg 20 mg 30 mg
 30% immediate-release component, 70% modified-release
 Dose: initially 10 mg once daily in the morning before
breakfast, increased gradually at weekly intervals if
necessary, max. 100 mg daily
 Contents of capsule can be sprinkled on a tablespoon of
apple sauce (then swallowed immediately without chewing)

30. Medikinet XL® capsules (Flynn)
 Schedule 2 controlled drug
 5 mg 10 mg 20 mg 30 mg 40 mg
 50% immediate-release component, 50% modified-release
 Dose: initially 10 mg once daily in the morning with breakfast,
adjusted at weekly intervals according to response, max. 100 mg
daily
 Contents of capsule can be sprinkled on a tablespoon of apple
sauce or yoghurt (then swallowed immediately without chewing)

31. Stimulants Effects
Improved sustained attention
Reduced distractibility
Reduced impulsivity
Improve work performance and academic work
Positive effect on behaviour (reduces aggression and
disruptive behaviour)
Effective in 75% of adult ADHD cases.

32. Stimulants Side Effects
Insomnia
 Decreased Appetite (in 50-60%): Weight Loss
Headaches
Stomach aches (20-40%)
Mood changes/dysphoria
(Mild) Increases in Heart Rate and Blood Pressure
Tics (very rarely Tourette syndrome)
Psychosis
Seizures
Tolerance and dependence?

33. Non-Stimulant medication (second
line treatment option)
Noradrenaline reuptake inhibitor
-Strattera (atomoxetine)
Antidepressants (various mechanism of action)
buproprion
nortriptyline
desipramine
Alpha-2 Agonists
clonidine
guanfacine

34. Atomoxetine (Strattera)
Potent pre-synaptic, noradrenergic transport blocker
with low affinity for other neurotransmitters
Structurally similar to Fluoxetine
Optimal effects seen at 2 weeks
May be given as single daily dose or bd
Dispensed in a capsule that cannot be opened

35. Indications
Severe side effects to stimulants
If comorbidity: tics; substance abuse

36. Atomoxetine Dose
Initial: 40 mg once daily increased after at least 1 week to
80 mg
Usual maintenance dose is 80-100 mg daily
Adverse effects: hepatotoxicity, suicidal events,
cardiovascular (increased p, bp), growth
Not scheduled
Only medication approved for adult ADHD

37. Atomoxetine Side Effects
Appetite decreased, dry mouth, nausea (>10%) Usually
settles after 1st month of therapy
Insomnia >10%
Abdominal pain, constipation, dyspepsia,
Weight decrease 1-10% Usually settles after initial weight
loss
Palpitations, tachycardia, 1-10%
Erectile dysfunction, irregular menstruation,
Blood pressure increased 0.1-1% Monitor. Discontinue if
clinically indicated
Liver toxicity 0.001-0.1% Discontinue drug. Refer back to
consultant

38. Post-marketing Reports
Suicide-related events
Aggression, hostility and emotional labiality
Psychosis (including hallucinations)
Seizure
QT interval prolongation
Abnormal liver function tests, jaundice, hepatitis

39. Cautions
Methylphenidate: history of seizures, tics or family
history of Tourette or other movement disorders, known
drug dependence/history of drug
dependence/alcoholism, depression, psychosis.
Atomoxetine: Cardiovascular disease, QT interval
prolongation, psychosis/mania, history of seizures,
aggressive behaviour/hostility/emotional labiality,
hepatic impairment, pregnancy and lactation.

40. Contra-indication
Methylphenidate: anorexia nervosa, severe hypertension,
hyperthyroidism, angina pectoris, cardiac arrhythmia
Atomoxetine: Concomitant use or use within 2 weeks of
MAOI, narrow-angle glaucoma.

41. Interactions
Alcohol: Effects of methylphenidate possibly enhanced by
alcohol.
Methylphenidate possibly inhibits metabolism of SSRI’s and
TCA’s.
Metabolism of atomoxetine possibly inhibited by fluoxetine
and paroxetine
Antipsychotics: methylphenidate possibly increases side
effects of risperidone. Increased risk of ventricular
arrhythmias when atomoxetine given with antipsychotics
that prolong QT interval.

42. Shared Care Protocols
Funding threatens these protocols
The specialist will initiate treatment
Transfer of prescribing responsibility to GP when the
patient’s condition is stable and dose is specified
The GP should agree on this transfer
The specialist will continue to supply prescriptions
until transfer of the responsibilities.
There should be regular review of the patient (by the
specialist)
The specialist give advice on when and how to
change the dose, discontinue or refer back
The GP will monitor patient’s pulse, BP and weight

43. Pre-treatment assessment
Full history with a basic physical exam including height,
weight, pulse, blood pressure, and heart and lung
auscultation
If there is family or personal history of heart disease or the
cardiovascular examination is abnormal an ECG is
recommended.
Risk of self-harm and substance misuse should also be
assessed.
In the case of atomoxetine, previous history of liver disease
should be evaluated.

44. Clinical monitoring
To be done by the GP (if in agreement with the specialist) in
accordance with NICE recommendations
Weight: To be measured 3 and 6 months after initiation and
six monthly thereafter.
If evidence of weight loss monitor BMI, if weight loss
persists refer back to consultant.
Heart rate and Blood pressure: Chart before and after each
dose change and routinely every three months. Sustained
resting tachycardia, arrhythmia or clinically significant high
systolic blood pressure (on two occasions: consider dose
reduction and refer to specialist)

45. Duration of treatment
Should be continued “as long as clinically effective” with
regular reviews at least annually.
Effects of dosage changes or no treatment periods should
be evaluated.
Drug holidays may be useful to ascertain the need of
continuation of treatment.

46. ADHD in Pregnancy
Amphetamine, lisdexamfetamine,
methylphenidate, atomoxetine, bupropion, and
modafinil are all category C by FDA classification
(Bazire, 2012).
This category includes drugs where animal
studies have reported some harm without there
being any robust evidence in humans.
Both continuing and stopping drug treatment
carries risk.

47. Medication in Breastfeeding
Very little knowledge
Drugs licensed for children in general less risky
than those that have not been used in this
population.
A recent systematic review supports the idea that
very little methylphenidate reaches the infant
during breastfeeding (Bolea-Alamanac et al., 2013)

48. Conclusion
 Treatment of adult ADHD is crucial and it is the responsibility of
primary and secondary care.
 Treatment associated with significant benefits to the person and
society.
 There are clear guidance on efficacy of treatment with stimulants
and non-stimulants
 Addressing co-morbidity is important.
 Developing local shared protocols throughout the UK is crucial

49. References
 NICE, BAP and European consensus
 Wilens TE, Faraone SV, Biederman J, Gunawardene S. Does stimulant therapy of attention-
deficit/hyperactivity disorder beget later substance abuse? A meta-analytic review of the literature.
Pediatrics. 2003 Jan;111(1):179-85.
 Wilens TE, Adamson J, Monuteaux M, Faraone SV, et al. Impact of Prior Stimulant Treatment for
Attention-Deficit Hyperactivity Disorder in the Subsequent Risk for Cigarette Smoking, Alcohol, and
Drug Use Disorders in Adolescent Girls. Arch Pediatr Adolesc Med. 2008 October ; 162(10): 916–
921.
 Faraone SV, Sergeant J, Gillberg C, Biederman J. The worldwide prevalence of ADHD: is it an
American condition? World Psychiatry. 2003 Jun;2(2):104-13.
 Volkow ND, Wang GJ, Fowler JS, Logan J, et al. Relationship between blockade of dopamine
transporters by oral methylphenidate and the increases in extracellular dopamine: therapeutic
implications. Synapse. 2002;43:181–187.
 Pietrzaka RH, Mollicab CM, Maruffc P, Snyde PJ. Cognitive effects of immediate-release
methylphenidate in children with attention-deficit/hyperactivity disorder