Presentation on theme: "Dr Gordon Bates Huntercombe Hospital University of Birmingham"— Presentation transcript:
1 Dr Gordon Bates Huntercombe Hospital University of Birmingham Psychotherapeutics in Child Psychiatry THE BPPA - BAPA ANNUAL CONFERENCE 2011 Saturday 18th NovemberDr Gordon BatesHuntercombe HospitalUniversity of Birmingham
2 Overview Basic Principles Range of medications Antipsychotics AntidepressantsADHD treatments:StimulantsAtomoxetineAlpha agonists
3 Principles of Child Pharmacokinetics Children are not small adultsArea is less well researchedRates of absorption in children are faster and peak levels are reached faster (esp. liquids)
7 Principles of Child Pharmacokinetics II Hepatic metabolism is almost double adult rate in middle childhood and approaches adult rates by 15 yearsFat stores in children act to slow elimination of liposoluble drugs (e.g. fluoxetine, pimozide)Cytochrome P450 2d6 and 2c19 unaffected by age but remember racial effects
8 When to use Medication Is it bad enough? Is it pervasive? Have psychological strategies or environmental modification been tried?Is it part of a wider treatment package?Do parents and adolescent give consent?Is it licensed/unlicenced or off indication?Is it an emergency?Risk/Benefit analysis
9 How to use Medication Monotherapy is better than polypharmacy Develop a range of familiar drugsStart low and go slowReview frequentlyConsider use of rating scalesMonitor for side effectsMonitor for drug/drug interactionsPharmacogenomics: the future?
10 Range of Treatments Anxiolytics Sedatives and Melatonin Antipsychotics Antidepressants: FluoxetineMood stabilisersADHD treatmentsMostly unlicensed for children
11 Prescribing to children: Licensed or unlicensed in UK AntipsychoticChild (<12)Adolescent (12-18)ChlorpromazineYesHaloperidol oralHaloperidol IMNoPimozideTrifluoperazineYes (anxiety)SulpirideYes (>14)Zuclopenthixol IMAmisulpirideYes(>15)ClozapineYes(>16)Olanzapine oralOlanzapine IMRisperidone oralRisperidone IM
12 Antipsychotics Haloperidol and Chlorpromazine have license Unlicensed Olanzepine, Risperidone and Aripiprazole most commonly used in UK practiceWide range of usage:PsychosisBipolarTourette’sRapid tranquillisationMood swings in Borderline Personality DisorderIrritability in ADHD and Autism
13 NICE recommendationsPredominantly aimed at adults and remaining within product licence:Atypical antipsychotics (TA 43 June 2002)Core Interventions in Schizophrenia (CG 1 Dec 2002)Bipolar Disorder (CG38 July 2006)Violence & Acute behavioural disturbance (CG25 Feb 2005)
14 How to choose Personal experience Side effect profile Family history of responsePatient or carers preference“local expert”
15 Side Effects of Antipsychotics (Bazire 2007) DrugAntiChCardiacEPSELow BPSedationMinor O/DWt gainProlactinProconvulsantAripiprazole-+?Olanzapine+++++QuetiapineRisperidoneZotapineClozapineAmisulpiride?+ChlorpromazHaloperidol
16 AntidepressantsDepression in childhood and adolescence has similarities and differences to adulthoodResponse to medication is differentTricyclics ineffective in Childhood depressionSSRI controversy: suicidality and mood lability in early treatmentCSM and NICE guidance:Psychological therapies firstIf medication indicated only Fluoxetine first line
17 Father of Child Psychopharmacology 14 of 30 children showed a ”spectacular change in behavior… remarkably improved school performance”SerendipityGiven after pneumo- encephalographyChildren called them their “arithmetic pills”(Am J Psych 1937)
18 Potential Mechanisms of Action Dopamine-Reuptake inhibition and direct releaseMethylphenidateDexamphetamineDopamine-reuptake inhibitorModafanilNoradrenaline-AgonistsL-amphetamineNoradrenaline-reuptake inhibitorAtomoxetineAlpha 2 adrenergic - agonistsClonidineGuanfacine
20 Features of Stimulant activity Greatest effects on Attention and restlessnessLess useful for impulsive behavioursRapid actingShort half lifeClear dose effect relationshipWell established side effect profile
21 Dose Response of Methylphenidate on Attention in clinic and classroom (Rappoport et al 1987)
22 Efficacy of the stimulants Educational intent:to illustrate the efficacy of stimulant treatment according to various parametersSPEAKERS’ NOTESSo far, stimulants are the gold standard pharmaceutical treatment for ADHD. However, pharmaceutical management should not be expected to solve all the problems associated with ADHD symptoms.Responder rate (%) 75-90Methylphenidate 75Amphetamine 70Normalisation rate (%) 50-60Symptom improvement (%)Behaviour scales 30-50Effect size (SD)Behaviour highAttention 0.7 mediumIQ/ Performance tests 0.3 low
23 Long Acting Stimulants Time of effectCommentsMethylphenidateEquasym XL 6-8hrs School day coverMedikinetConcerta® XL 8-12hrs Sleep and appetiteDaytrana ® hrs TransdermalUS onlyAmphetamine compoundsAdderall XR 6-8hrs Import onlyVyvanase 12-14hrs Prodrug, ltd abuse(lisdexamfetamine) Awaiting UK approvalMedication management plays a central role in the management of most patients with ADHD.Stimulants are recommended as first-line therapy for patients with ADHD.This slide shows the advantages and disadvantages of various stimulants used to treat ADHD.
24 Transdermal Methylphenidate (Daytrana) Doses: 10mg, 15mg, 20mg 30mgApplied to hip each morningStays on after swimming or bathingIrritation rareSuggested use for 9 hours but effects last 3 hours after removalHeal and Pierce CNS drugs (2006)
25 Lisdexamfetamine (Vyvanase) Metabolised in GI tract to Lysine and DexamphetamineDoses: 30mg, 50mg, 70mgLittle euphoric effect reducing abuse potentialClin Ther 2007;29:
26 Side Effects Anorexia, weight loss Give with meals Use supplements Dietary adviceInsomniaGive earlierUse shorter acting prepConsider melatonin/clonidineReboundChange to long acting prepAssess timing and overlapDysphoriaConsider comorbidity and treatChange to long acting or alternative stimulant
27 Cardiovascular Risk Sudden death rates in General Population: 0.6-6/100,000 children per year1/1000 adults per yearEstimated sudden death rate on Stimulants:0.25/100,000 people per year based on Rx data0.5/100,000 people per year (assuming 50% under- reporting)FDA reevaluation 24/3/2006:No additional risk in medically healthy children
28 Atomoxetine Recent analyses suggest: Children similar to adolescents for outcomeMonitor height and weight esp in younger childrenSome response by week 2 but continue to weeksReduction in irritability precedes core symptom improvements
29 Atomoxetine Niches Treatment resistance, partial response Intolerable side effectsImportance of all day coverPossible substance misuse or diversionComorbid anxiety disorderTic disorder
30 Atomoxetine Side Effects: Somnolence, insomnia, nausea, headache, reduced appetite, abdominal discomfort, raised BP and pulse, sexual dysfunctionDrug Interactions:Care with some SSRIs (fluoxetine and paroxetine)No interaction with stimulants or alcohol
31 Atomoxetine Rare hepatitis reported 1 confirmed case in 3.4 million prescriptions1 further suspected case in 3.4 million prescriptionsImplications: Discuss rare event not routine LFTsKnown increase in mood lability in 3%Possible slight increase in suicidal ideation0.037% Atomoxetine v 0% PlaceboOne suicide attempt/1357 studied
32 Clonidine Used for ADHD therapy and night sedation Better for restlessness than attentionUseful but popularity waning due to side fxGood for tics and comorbid ADHDDoses 0.05 mg-0.2 mg tdsEvening reboundPatch available but import onlyCare with joint prescribing (ECG recommended)Look out for sedation, hypotension, depression, constipation and dry mouth
33 Clonidine controversy Clonidine and Methylphenidate3 case reports of sudden deathFDA review decided no causal linkOther relevant factors in all casesClonidine4 case reports of cardiac arrythmias, one with congenital malformationUse with care if history or family history of collapse. ECG sensible for combination.
34 Guanfacine Possible alternative to Clonidine Half life of 18 hours in adults1 open label study and one RCT show efficacy:Scahill et al JAACAP 2001Spencer et al JAACAP 2009Similar to clonidine but less sedating, more headaches and insomnia? Better for attention than hyperactivityRecent licence in US
35 ConclusionsVariations in child pharmacokinetics can lead to less predictable responsesRequirement of closer monitoring and shared care with parentsMany adult approved drugs are given off licence to childrenMedications have a restricted but important part in holistic care planMedications are often given symptomatically rather than for diagnosis
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