Pharmacological Management of ADHD by Dr Uju Ugochukw


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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.

Published in: Health & Medicine
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Pharmacological Management of ADHD by Dr Uju Ugochukw

  1. 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 Reason: I am the author of this document Location: Date: 2014-03-30 15:37+01:00
  2. 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. 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. 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. 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. 6. Why should we treat adults with ADHD? Criminal behaviour reduced by 32% in men, 41% in women (Lichtenstein et al., 2012)
  7. 7.
  8. 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. 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. 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. 11. NICE/BAP Guidelines Drug treatment should be the first- line treatment unless the person would prefer a psychological approach
  12. 12. NICE Guidelines Drug treatment should always form part of a comprehensive treatment programme that addresses psychological, behavioural and educational or occupational needs.
  13. 13. Medication for ADHD Stimulants Methylphenidate Dexamphetamine Lisdexamphetamine Non-stimulants Atomoxetine Bupropion, Clonidine, Guanfacine, Modafinil, Tricyclics Venlafaxine 13
  14. 14. NICE/BAP Guidelines Methylphenidate is generally first line treatment
  15. 15. Meta-analysis (Faraone et al, 2004) Mean effect size of 0.9, z=4.3, p<0.001
  16. 16. How do the drugs work? They increase dopamine and/or noradrenaline function in the brain
  17. 17. Substantia nigraBasal ganglia Two main dopamine pathways Professor David Nutt
  18. 18. Substantia nigraBasal ganglia Motor function Professor David Nutt
  19. 19. Substantia nigraBasal ganglia Motor function Attention & planning Professor David Nutt
  20. 20. Dopamine – cortical-subcortical interactions Prefrontal cortex Basal ganglia VTA Substantia Niagra - Professor David Nutt
  21. 21. Theory of attention deficit Prefrontal cortex Basal ganglia VTA Substantia Niagra - DA deficiency Inattention Professor David Nutt
  22. 22. Theory of AD Hyperactivity disorder Prefrontal cortex Basal ganglia VTA Substantia nigra - Inattention Excessive activity Reduced descending inhibition Professor David Nutt
  23. 23. Stimulant action Prefrontal cortex Basal ganglia VTA Substantia nigra - Inattention Excessive activity stimulants Professor David Nutt
  24. 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. 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. 26. How to cope?
  27. 27. What should be treated first?  Treat the most annoying problem first  Review Diagnosis  Treat ADHD 27
  28. 28. What should be treated first? (Stahl 2009)
  29. 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. 30. Pre-treatment Assessment  BP and pulse  Weight  ECG, ECHO if necessary  Risk of abuse or diversion of psycho- stimulants
  31. 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. 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. 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. 34. Lisdexamphetamine Dimesylate (Elvanse)  Prodrug  Ingredients are inactive unless swallowed  Converted to d-amphetamine in the red blood cells  Low abuse potential
  35. 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. 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. 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. 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. 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. 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. 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. 42. Adverse effects  Insomnia  Headache  Usually temporary  Nausea and vomiting  Particularly with Atomoxetine
  43. 43. Other adverse effects  Abdominal pain  Anxiety  Dizziness  Dry mouth  Rashes/pruritus  Psychotic symptoms  Rare  Stop stimulants  Use Atomoxetine
  44. 44. Third-line medications  Bupropion (licensed as anti-smoking)  Alpha 2 agonists  Clonidine  Guanfacine ( can cause weight gain)  Tricyclic antidepressants  Imipramine  Modafinil
  45. 45. Clonidine  Often used as an adjunct  Side effects  Sedation  Hypotension  Dry mouth  Rebound hypertension can be dangerous in chaotic patients
  46. 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. 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. 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. 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. 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. 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. 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. 53. Questions? 53
  54. 54. Thank you 54