MRCPsych Pharmacology of ADHD treatment Dr Xanthe Barkla, Consultant Child and Adolescent Psychiatrist 04 01 17
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.
4.3 Pharmacodynamics 4.3.2 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 Adverse Drug Reactions (ADRs) 4.4.3 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). 4.4.5 Prescribing of controlled drugs.
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.
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
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
Attention Deficit Hyperactivity Disorder (ADHD) Core features of ADHD Inattention Hyperactivity Impulsivity Medication is to target these
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
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
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
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
Medication options Methylphenidate Atomoxetine Lisdexamfetamine
Methylphenidate Atomoxetine Lisdexamfetamine
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
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
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
Proportions Immediate release/ Modified release Medikinet XL = 50 / 50% Equasym XL = 30 / 70% Concerta XL = 22 / 78% This explains duration of action
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
MONITORING Height Weight Pulse Blood pressure Plot on centile charts (growth chart, BP centile chart)
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
Controlled drugs ID to collect prescriptions 30 days at a time If lost police report Consider possibility of misuse and diversion
Methylphenidate Atomoxetine Lisdexamfetamine
MODE OF ACTION Boosts neurotransmitter norepinephrine/ noradrenaline and may also increase dopamine in prefrontal cortex Blocks norepinephrine reuptake pumps 24 hour cover, unlike stimulants
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
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
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
Methylphenidate Atomoxetine Lisdexamfetamine
MODE OF ACTION Absorbed by GI tract, converted to dextroamphetamine This increases norepinephrine and dopamine by blocking their reuptake and facilitating their release
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.
SIDE-EFFECTS Insomnia Headache Worsening of tics Loss of appetite Dry mouth Constipation Growth
Monitoring: As per stimulants Height Weight Pulse Blood pressure Plot on centile charts
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 10 12 hour duration of action
Methylphenidate Atomoxetine Lisdexamfetamine
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
Useful resources NICE guideline number 72 https://www.nice.org.uk/guidance/cg72 Stahl s prescriber s guide
Thank you for listening Questions/ comments Stahl s prescribing guidance