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?

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Thank you

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