Dr Uju Ugochukwu Consultant Adult Psychiatrist Youth Mental Health Service/Early Intervention in Psychosis Great Yarmouth and Waveney (Norfolk and Suffolk NHS Trust) This presentation was presented at ADHD Training Day at Dunston Hall in Norwich on 28 March 2014. The day is free for all staff and is kindly sponsored by Eli Lilly Neuroscience plus is supported by the Trust NDD Steering Group and the Postgraduate Department.

1. Pharmacological
Management of ADHD in
Adults
Dr Uju Ugochukwu
Consultant Adult Psychiatrist
Youth Mental Health Service/Early
Intervention in Psychosis
Great Yarmouth and Waveney
Obianuju
Ugochukwu
(MRCPsych)
Digitally signed by Obianuju Ugochukwu
(MRCPsych)
DN: cn=Obianuju Ugochukwu (MRCPsych)
gn=Obianuju Ugochukwu (MRCPsych) c=United
Kingdom l=GB e=uju@doctors.org.uk
Reason: I am the author of this document
Location:
Date: 2014-03-30 15:37+01:00

2. Outline
 Importance of treating ADHD in adults
 How the drugs work
 Case vignette and treatment
 Common adverse effects and
management
 Stimulant drugs and abuse potential

3. Why should we treat adults with
ADHD?
It is relatively common
 Prevalence rates varies 3 - 4%
(Faraone et al 2005, Kessler et al 2006, Simon et al 2009)

4. Why should we treat adults
with ADHD?
70-80% of children
with ADHD
continue to have
symptoms as adults
(Kooij et al 2010)
4

5. High rates of comorbidity
30%
70%
No comorbidity Comorbidity
5
Average number of comorbid disorders in
referred patients with ADHD is three (kooij et al 2001, 2004,
Biederman et al 1993)

6. Why should we treat adults
with ADHD?
Criminal behaviour reduced by 32%
in men, 41% in women (Lichtenstein et al., 2012)

7. www.medscape.org

8. How many adults with ADHD requiring
medication are thought to receive it?
A. 50%
B. About 60%
C. Less than 10%
D. 30%
E. 20%
BAP Guidelines

9. How many adults with ADHD requiring
medication are thought to receive it?
A. 50%
B. About 60%
C. Less than 10%
D. 30%
E. 20%
BAP Guidelines

10. Prevalence of pharmacologically treated attention deficit hyperactivity disorder
(methylphenidate, dexamfetamine or atomoxetine) in patients aged 6-years and
over in UK general practice (with 95% confidence intervals) McCarthy et al. BMC Pediatrics
2012 12:78

11. NICE/BAP Guidelines
Drug treatment should be the first-
line treatment unless the person
would prefer a psychological
approach

12. NICE Guidelines
Drug treatment should always form part of a
comprehensive treatment programme that
addresses psychological, behavioural and
educational or occupational needs.

13. Medication for ADHD
Stimulants
Methylphenidate
Dexamphetamine
Lisdexamphetamine
Non-stimulants
Atomoxetine
Bupropion,
Clonidine,
Guanfacine,
Modafinil, Tricyclics
Venlafaxine
13

14. NICE/BAP Guidelines
Methylphenidate
is generally first
line treatment

15. Meta-analysis (Faraone et al, 2004)
Mean effect size of 0.9, z=4.3, p<0.001

16. How do the drugs work?
They increase dopamine and/or
noradrenaline function in the
brain

17. Substantia
nigraBasal
ganglia
Two main dopamine pathways
Professor David Nutt

18. Substantia
nigraBasal
ganglia
Motor
function
Professor David Nutt

19. Substantia
nigraBasal
ganglia
Motor
function
Attention
& planning
Professor David Nutt

20. Dopamine – cortical-subcortical
interactions
Prefrontal
cortex
Basal
ganglia
VTA
Substantia
Niagra
-
Professor David Nutt

21. Theory of attention deficit
Prefrontal
cortex
Basal ganglia
VTA
Substantia
Niagra
-
DA
deficiency
Inattention
Professor David Nutt

22. Theory of AD Hyperactivity disorder
Prefrontal
cortex
Basal
ganglia
VTA
Substantia
nigra
-
Inattention
Excessive
activity
Reduced
descending
inhibition
Professor David Nutt

23. Stimulant action
Prefrontal
cortex
Basal
ganglia
VTA
Substantia
nigra
-
Inattention
Excessive
activity
stimulants
Professor David Nutt

24. BAP Guidelines 24
Neurotransmitter Mechanism of action
Monoamine
releasing agents
Noradrenaline
selective
ADHD Drugs
Monoamine
reuptake
inhibitors
Noradrenaline
+
Dopamine
methylphenidate
AtomoxetineAtomoxetine
Methylphenidate
d-Amphetamine
Lisdexamphetamine
Dopamine/
adrenaline
reuptake
inhibitors
d-Amphetamine
Lisdexampheta
mine

25. Case vignette
 Joe a 38-year-old man presents in clinic with anxiety and low mood.
 He is having increasing problems in dealing with work and family
issues. He works in advertising at a large company.
 Inability to complete projects in a timely and error-free manner.
 Has trouble concentrating at work because it is so boring; then he
gets behind because he puts off the really "mind-numbing" tasks in
projects.
 His habit of misplacing items like his keys and forgetting family
activities has caused tension recently with his wife. His patience has
worn thin with his really hyper 12-year-old son.

26. How to cope?

27. What should be treated
first?
 Treat the most annoying problem
first
 Review Diagnosis
 Treat ADHD
27

28. What should be treated first? (Stahl 2009)

29. Pre-treatment Assessment (UKAAN
website)
 Have you been told by your doctor that you have
heart disease
 Do you ever get chest pain on exertion?
 Have you ever passed out or fainted whilst
exercising?
 Has anyone in your family developed heart
disease before the age of 60?
 Has anyone in your family died of heart disease
before the age of 60?

30. Pre-treatment Assessment
 BP and pulse
 Weight
 ECG, ECHO if necessary
 Risk of abuse or diversion of psycho-
stimulants

31. Pre-treatment Assessment
 Atomoxetine
 History of liver disease
 Patients should be told how to recognise
symptoms (darkening of urine, jaundice,
malaise, nausea)
 Routine Liver Function Test not recommended
 History of suicidal behaviour
 Inform patient of risk of suicidal ideation

32. Stimulants - Methylphenidate
Drug Ritalin Concerta XL Equasym XL Medikinet XL
Ratio of short
acting: long
acting
Short-acting 22:78 30:70 50:50
Duration of
action
3-4 hours Up to 12 hours 8 hours 7- 8 hours
Dosing Twice daily
or three times
daily
18mg/day
increase weekly
by 9 to 18mg
10mg/day
increase weekly
by 10mg
10mg/day
increase weekly
by 10mg
Maximum doses 100mg/day 108mg/day 100mg/day 100mg/day
Food intake Unaffected by
food intake.
Swallowed
whole
Before
breakfast
With or after
breakfast

33. Stimulants - Amphetamines
Drug Dexamphetamine Lisdexamphetamin
e
(Elvanse)
Duration of action 4 – 5 hours Up to 13 hours
Dosing Initially 5mg bd
Increased at weekly
intervals
30mg once-daily
Maximum doses 60mg daily 70mg

34. Lisdexamphetamine
Dimesylate (Elvanse)
 Prodrug
 Ingredients are inactive unless
swallowed
 Converted to d-amphetamine in the
red blood cells
 Low abuse potential

35. Case Vignette- Joe
 Joe is happy to for a trial of
methylphenidate
 Start Concerta XL 18mg
 Prescribing for controlled drugs
 Dose titrated over 6 weeks or more
35

36. When do we use Atomoxetine?
 Often as second line when
Methylphenidate ineffective or not
tolerated
 Substance misuse or risk of
diversion
 Psychosis
36

37. Atomoxetine
 Weight > 70kg = initially 40mg daily
 Increase dose by 20mg/day ( max
100mg/daily
 Weight < 70kg = 0.5mg/kg daily
 Takes a longer time to work
 At least 12 weeks on therapeutic dose (BAP Guidelines)
 Metabolised via CYP2D6 pathway in the liver.
Poor metabolisers need slower titration

38. Monitoring and titration
 Monitor response to treatment using rating
scales
 Monitor BP and pulse after each dose change
then every 3 months
 Monitor weight every 6 months
 If no effect or patient cannot tolerate high
doses, switch to non-stimulant

39. What do the drugs do?
 Greater control
 Reduced impulsivity and irritability
 Improved concentration
 Improved tendency to organise and tidy
up
 Rating scales – 30% reduction in
severity

40. What do the drugs do?
 Improve self-esteem
 Reduce anger outbursts
 Improves mood swings
 Improves social and family
functions
Kooij et al 2010 European consensus
statement

41. Adverse Effects
 Decreased appetite and weight loss
 Large breakfast, late supper, taking
medication either with or after food
 Improves with time
 Increased blood pressure
 Rarely significant
 Palpitations
 Usually at start of treatment, cut out
caffeine

42. Adverse effects
 Insomnia
 Headache
 Usually temporary
 Nausea and vomiting
 Particularly with Atomoxetine

43. Other adverse effects
 Abdominal pain
 Anxiety
 Dizziness
 Dry mouth
 Rashes/pruritus
 Psychotic
symptoms
 Rare
 Stop stimulants
 Use
Atomoxetine

44. Third-line medications
 Bupropion (licensed as anti-smoking)
 Alpha 2 agonists
 Clonidine
 Guanfacine ( can cause weight gain)
 Tricyclic antidepressants
 Imipramine
 Modafinil

45. Clonidine
 Often used as an adjunct
 Side effects
 Sedation
 Hypotension
 Dry mouth
 Rebound hypertension can be
dangerous in chaotic patients

46. How long should we treat?
 For as long as it is clinically
effective
 Effect of missed doses should be
evaluated
 Review need for medication at
least annually

47. Combination treatment
 Limited evidence of what works
 Combination of methylphenidate and
Atomoxetine has been tried in poor
response cases
 Combination of ER and IR formulations
to manage side-effects
 Combination of methylphenidate and
amphetamine is not recommended
47

48. Pregnancy and Lactation
 Limited evidence so consider risks and benefits
 Illicit stimulants causes low birth weight, prematurity,
increased morbidity (Humphrey’s et al 2007)
 No need to discontinue during lactation if baby was
exposed in pregnancy
 Systematic review that suggests little methylphenidate
reaches the infant during breast feeding. But little
evidence about its longer term effect. (BAP)
 Contact NSFT pharmacy and UK Teratology Information
Service (UKTIS) for latest information
48

49. Are these stimulant drugs
prone to abuse?
 Abuse potential relates to route of
administration
 Euphoric properties more likely with IV
injection or intranasal use
 You can crush Ritalin IR and snort it
 If worried, use long acting
methylphenidate, Atomoxetine or
Lisdexamphetamine

50. Proportion of patients aged 15 years in 1999 remaining in treatment for each 1-year change in
age (n=44) (expected persistence 83%).
McCarthy S et al. BJP 2009;194:273-277
©2009 by The Royal College of Psychiatrists

51. Adult ADHD Clinic
 Special Interest Clinic, since 2006
 Now under the Youth Service
 Majority diagnosed as children but
discontinued medication
 About 60 patients in current clinic
 Majority on Concerta XL or Atomoxetine
 Non-attendance is a big problem

52. Key messages
 ADHD is common and comorbidity is high
 Treatment is not more complex than other
common psychiatric conditions.
 Treating patients can be very rewarding.
 Inadequate dosing is a common cause of
non-response
 Evidence does not support significant
abuse of prescribed stimulants

53. Questions?
53

54. Thank you
54