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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.
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PharmacologicalManagement of ADHD inAdults
Dr Uju UgochukwuConsultant Adult Psychiatrist
Youth Mental Health Service/EarlyIntervention in Psychosis
Great Yarmouth and Waveney
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
Why should we treat adults withADHD?
It is relatively common Prevalence rates varies 3 - 4%
(Faraone et al 2005, Kessler et al 2006, Simon et al 2009)
Why should we treat adultswith ADHD?
70-80% of childrenwith ADHDcontinue to havesymptoms as adults(Kooij et al 2010)
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High rates of comorbidity
30%
70%
No comorbidity Comorbidity
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Average number of comorbid disorders inreferred patients with ADHD is three (kooij et al 2001, 2004,Biederman et al 1993)
Why should we treat adultswith ADHD?
Criminal behaviour reduced by 32%in men, 41% in women (Lichtenstein et al., 2012)
www.medscape.org
How many adults with ADHD requiringmedication are thought to receive it?
A. 50%B. About 60%C. Less than 10%D. 30%E. 20%
BAP Guidelines
How many adults with ADHD requiringmedication are thought to receive it?
A. 50%B. About 60%C. Less than 10%D. 30%E. 20%
BAP Guidelines
Prevalence of pharmacologically treated attention deficit hyperactivity disorder(methylphenidate, dexamfetamine or atomoxetine) in patients aged 6-years andover in UK general practice (with 95% confidence intervals) McCarthy et al. BMC Pediatrics2012 12:78
NICE/BAP Guidelines
Drug treatment should be the first-line treatment unless the personwould prefer a psychologicalapproach
NICE Guidelines
Drug treatment should always form part of acomprehensive treatment programme thataddresses psychological, behavioural andeducational or occupational needs.
Medication for ADHD
Stimulants
MethylphenidateDexamphetamine
Lisdexamphetamine
Non-stimulants
Atomoxetine
Bupropion,Clonidine,
Guanfacine,Modafinil, Tricyclics
Venlafaxine
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NICE/BAP Guidelines
Methylphenidateis generally firstline treatment
Meta-analysis (Faraone et al, 2004)Mean effect size of 0.9, z=4.3, p<0.001
How do the drugs work?
They increase dopamine and/ornoradrenaline function in thebrain
SubstantianigraBasal
ganglia
Two main dopamine pathwaysProfessor David Nutt
SubstantianigraBasal
ganglia
Motorfunction
Professor David Nutt
SubstantianigraBasal
ganglia
Motorfunction
Attention
& planning
Professor David Nutt
Dopamine – cortical-subcorticalinteractions
Prefrontalcortex
Basalganglia
VTA
SubstantiaNiagra
-
Professor David Nutt
Theory of attention deficit
Prefrontalcortex
Basal ganglia
VTA
SubstantiaNiagra
-
DAdeficiency
Inattention
Professor David Nutt
Theory of AD Hyperactivity disorder
Prefrontalcortex
Basalganglia
VTA
Substantianigra
-
Inattention
Excessiveactivity
Reduceddescendinginhibition
Professor David Nutt
Stimulant action
Prefrontalcortex
Basalganglia
VTA
Substantianigra
-
Inattention
Excessiveactivity
stimulants
Professor David Nutt
BAP Guidelines 24
Neurotransmitter Mechanism of action
Monoaminereleasing agents
Noradrenalineselective
ADHD Drugs
Monoaminereuptakeinhibitors
Noradrenaline+
Dopamine
methylphenidate
AtomoxetineAtomoxetine
Methylphenidated-AmphetamineLisdexamphetamine
Dopamine/adrenalinereuptakeinhibitors
d-AmphetamineLisdexamphetamine
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 familyissues. 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 hegets behind because he puts off the really "mind-numbing" tasks inprojects.
His habit of misplacing items like his keys and forgetting familyactivities has caused tension recently with his wife. His patience hasworn thin with his really hyper 12-year-old son.
How to cope?
What should be treatedfirst?
Treat the most annoying problemfirst
Review Diagnosis Treat ADHD
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What should be treated first? (Stahl 2009)
Pre-treatment Assessment (UKAAN
website)
Have you been told by your doctor that you haveheart 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?
Pre-treatment Assessment
BP and pulse Weight ECG, ECHO if necessary Risk of abuse or diversion of psycho-
stimulants
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
Stimulants - MethylphenidateDrug Ritalin Concerta XL Equasym XL Medikinet XL
Ratio of shortacting: longacting
Short-acting 22:78 30:70 50:50
Duration ofaction
3-4 hours Up to 12 hours 8 hours 7- 8 hours
Dosing Twice dailyor three timesdaily
18mg/dayincrease weeklyby 9 to 18mg
10mg/dayincrease weeklyby 10mg
10mg/dayincrease weeklyby 10mg
Maximum doses 100mg/day 108mg/day 100mg/day 100mg/day
Food intake Unaffected byfood intake.Swallowedwhole
Beforebreakfast
With or afterbreakfast
Stimulants - AmphetaminesDrug Dexamphetamine Lisdexamphetamin
e(Elvanse)
Duration of action 4 – 5 hours Up to 13 hours
Dosing Initially 5mg bdIncreased at weeklyintervals
30mg once-daily
Maximum doses 60mg daily 70mg
LisdexamphetamineDimesylate (Elvanse)
Prodrug Ingredients are inactive unless
swallowed Converted to d-amphetamine in the
red blood cells Low abuse potential
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
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When do we use Atomoxetine?
Often as second line whenMethylphenidate ineffective or nottolerated
Substance misuse or risk ofdiversion
Psychosis
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Atomoxetine Weight > 70kg = initially 40mg daily
Increase dose by 20mg/day ( max100mg/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
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
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
What do the drugs do?
Improve self-esteem Reduce anger outbursts Improves mood swings Improves social and family
functions
Kooij et al 2010 European consensusstatement
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
Adverse effects
InsomniaHeadacheUsually temporary
Nausea and vomitingParticularly with Atomoxetine
Other adverse effects Abdominal pain Anxiety Dizziness Dry mouth Rashes/pruritus
Psychoticsymptoms Rare Stop stimulants Use
Atomoxetine
Third-line medications Bupropion (licensed as anti-smoking) Alpha 2 agonists
Clonidine Guanfacine ( can cause weight gain)
Tricyclic antidepressants Imipramine
Modafinil
Clonidine
Often used as an adjunct Side effects
Sedation Hypotension Dry mouth Rebound hypertension can be
dangerous in chaotic patients
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
Combination treatment Limited evidence of what works Combination of methylphenidate and
Atomoxetine has been tried in poorresponse cases
Combination of ER and IR formulationsto manage side-effects
Combination of methylphenidate andamphetamine is not recommended
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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 wasexposed in pregnancy
Systematic review that suggests little methylphenidatereaches the infant during breast feeding. But littleevidence about its longer term effect. (BAP)
Contact NSFT pharmacy and UK Teratology InformationService (UKTIS) for latest information
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Are these stimulant drugsprone to abuse?
Abuse potential relates to route ofadministration
Euphoric properties more likely with IVinjection or intranasal use
You can crush Ritalin IR and snort it If worried, use long acting
methylphenidate, Atomoxetine orLisdexamphetamine
Proportion of patients aged 15 years in 1999 remaining in treatment for each 1-year change inage (n=44) (expected persistence 83%).
McCarthy S et al. BJP 2009;194:273-277
©2009 by The Royal College of Psychiatrists
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
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
Questions?
53
Thank you
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