MRCPsych Pharmacology of ADHD treatment. Dr Xanthe Barkla, Consultant Child and Adolescent Psychiatrist

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1 MRCPsych Pharmacology of ADHD treatment Dr Xanthe Barkla, Consultant Child and Adolescent Psychiatrist

2 Curriculum mapping MRCPsych Paper A(ii) covers clinical psychopharmacology MRCPsych Syllabus: Section 4: Clinical Psychopharmacology The trainee will demonstrate knowledge of psychopharmacology. This knowledge will include pharmacological action, clinical indications, side effects, drug interactions, toxicity and appropriate prescribing practice.

3 4.3 Pharmacodynamics The principal CNS pharmacology of the main groups of drugs used in psychiatry with particular attention to their postulated modes of action in achieving therapeutic affect: at both molecular/synaptic and systems levels.

4 4.4 Adverse Drug Reactions (ADRs) The importance of assessing risks and benefits for every individual patient in relation to his medication. Risks and benefits of psychotropic drugs in acute, short- and longterm use including effects of withdrawal. Where appropriate, knowledge of official guidance on the use of particular drugs (e.g. the Royal College Guidelines on the use of Benzodiazepines, NICE guidance) Prescribing of controlled drugs.

5 10. CHILD AND ADOLESCENT PSYCHIATRY Trainees shall demonstrate a general knowledge of Child and Adolescent Psychiatry. This includes knowledge of the assessment and treatment of children and adolescents, knowledge of disorders that are usually first diagnosed in infancy, childhood or adolescence and developmental disabilities.

6 Outline BY THE END OF THE SESSION YOU WILL HAVE A KNOWLEDGE OF: Core symptoms of ADHD NICE guidance For each of the 3 main medications: Mode of action Clinical indications Side-effects Drug interactions/ toxicity Prescribing practice Prescribing of controlled drugs

7 What this talk won t cover Dosing regimens These will be learnt on the job BNF for children guidance on starting doses and maximum doses (based on weight) Please ask questions as we go along if interested in dosing

8 Attention Deficit Hyperactivity Disorder (ADHD) Core features of ADHD Inattention Hyperactivity Impulsivity Medication is to target these

9 Attention Deficit Hyperactivity Disorder (ADHD) management NICE guidelines Behavioural management (parent training) Pharmacological management NOT indicated first line Indicated only in severe ADHD first line

10 NICE Guideline DIAGNOSIS AND MANAGEMENT OF ADHD (GUIDELINE NUMBER 72) Drug treatment should only be started by a healthcare professional with expertise in ADHD Always form part of a comprehensive treatment plan that includes psychological, behavioural and educational advice and interventions

11 Choice of drug treatment Decide which drug treatment to use based on: Co-morbidity (tics, Tourette s, epilepsy) Side-effect profile Individual preference Potential for diversion/ misuse

12 General principles for prescribing in children and young people Start low, go slow Gradually increase the dose until there is no further improvement in symptoms, behaviour AND/ OR side-effects are tolerable Slower dose titration if tics/ seizures are present Regular monitoring and recording of sideeffects +/- dose alterations

13 Medication options Methylphenidate Atomoxetine Lisdexamfetamine

14 Methylphenidate Atomoxetine Lisdexamfetamine

15 Methylphenidate MODE OF ACTION Increases norepinephrine and especially dopamine by blocking their reuptake Enhancing norepinephrine and dopamine may improve attention, concentration and executive functioning How long it takes to work: some immediate effects within first dosing, several weeks for maximum therapeutic benefit

16 Methylphenidate CLINICAL INDICATIONS Usually first medication started (for ADHD without significant co-morbidity) IMMEDIATE RELEASE More flexible dosing During initial titration to determine correct dosing levels MODIFIED-RELEASE Convenience (once-daily), reduces stigma Pharmacokinetic profile Reduces need for storing/ administering controlled medications in school

17 Pharmacokinetics and pharmacodynamics of different preparations IMMEDIATE RELEASE Methylphenidate IR (Ritalin) = 4 hours Therefore 2 3 times daily dosing MODIFIED RELEASE Medikinet XL/ Equasym XL = 8 hours Concerta XL = 12 hours Therefore once daily dosing

18 Proportions Immediate release/ Modified release Medikinet XL = 50 / 50% Equasym XL = 30 / 70% Concerta XL = 22 / 78% This explains duration of action

19 SIDE-EFFECTS Closely monitor children and young people starting drug treatment for side-effects Insomnia Headache Nausea Abdominal pain Loss of appetite Hypertension Cardiac arrhythmias Final height

20 MONITORING Height Weight Pulse Blood pressure Plot on centile charts (growth chart, BP centile chart)

21 DRUG INTERACTIONS/ TOXICITY May affect blood pressure use with caution in those on BP medication May cause sudden cardiac death in those with pre-existing cardiac abnormalities May worsen tics/ Tourette s Risk of diversion/ abuse PRESCRIBING PRACTICE Start low, build up, balancing with side-effects Dose will depend on preparation used 2.1mg/kg maximum

22 Controlled drugs ID to collect prescriptions 30 days at a time If lost police report Consider possibility of misuse and diversion

23 Methylphenidate Atomoxetine Lisdexamfetamine

24 MODE OF ACTION Boosts neurotransmitter norepinephrine/ noradrenaline and may also increase dopamine in prefrontal cortex Blocks norepinephrine reuptake pumps 24 hour cover, unlike stimulants

25 Atomoxetine CLINICAL INDICATIONS Atomoxetine may be considered as first choice in the presence of: Current or past substance misuse Tics Strong family preference to avoid stimulants 24 hour duration of action is particularly strongly required How long it takes to work: may continue to improve up to 8 to 12 weeks

26 SIDE-EFFECTS Sedation, fatigue, loss of appetite, increased blood pressure Closely monitor for/ ask parents to report: Agitation Irritability Suicidal thinking Self-harming behaviour Unusual changes in behaviour Liver damage (abdominal pain/ unexplained nausea/ malaise/ darkening of urine/ jaundice) Particularly in initial months of treatment OR after dose change

27 DRUG INTERACTIONS/ TOXICITY Plasma concentrations of Atomoxetine can be increased by drugs that inhibit CYP450 so Atomoxetine dose may need to be reduced Monitor weight and height, may need to stop if not growing Monitor pulse and blood pressure PRESCRIBING PRACTICE Once daily dosing 1.2mg/kg maximum

28 Methylphenidate Atomoxetine Lisdexamfetamine

29 MODE OF ACTION Absorbed by GI tract, converted to dextroamphetamine This increases norepinephrine and dopamine by blocking their reuptake and facilitating their release

30 Lisdexamfetamine CLINICAL INDICATIONS Licensed as a second line treatment Used when response to previous methylphenidate or atomoxetine treatment is inadequate How long it takes to work: some immediate effects can be seen within first dosing, can take several weeks to attain maximum benefit.

31 SIDE-EFFECTS Insomnia Headache Worsening of tics Loss of appetite Dry mouth Constipation Growth

32 Monitoring: As per stimulants Height Weight Pulse Blood pressure Plot on centile charts

33 DRUG INTERACTIONS/ TOXICITY Beware impact on blood pressure May need to stop if not growing/ gaining weight May worsen tics Is a controlled drug: be aware of risk of diversion PRESCRIBING PRACTICE Dose 30mg/day then increase if needed (10mg at a time) until maximum dose hour duration of action

34 Methylphenidate Atomoxetine Lisdexamfetamine

35 General principles for duration of treatment and follow-up Continue treatment as long as it is effective Review AT LEAST annually in children and young people Weigh up clinical need, benefits and sideeffects Individual choice

36 Useful resources NICE guideline number 72 Stahl s prescriber s guide

37 Thank you for listening Questions/ comments Stahl s prescribing guidance

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