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Psychotherapeutics in Child Psychiatry Psychotherapeutics in Child Psychiatry THE BPPA - BAPA ANNUAL CONFERENCE 2011 Saturday 18 th November Dr Gordon.

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Presentation on theme: "Psychotherapeutics in Child Psychiatry Psychotherapeutics in Child Psychiatry THE BPPA - BAPA ANNUAL CONFERENCE 2011 Saturday 18 th November Dr Gordon."— Presentation transcript:

1 Psychotherapeutics in Child Psychiatry Psychotherapeutics in Child Psychiatry THE BPPA - BAPA ANNUAL CONFERENCE 2011 Saturday 18 th November Dr Gordon Bates Huntercombe Hospital University of Birmingham

2 Overview Basic Principles Range of medications Antipsychotics Antidepressants ADHD treatments: Stimulants Atomoxetine Alpha agonists

3 Principles of Child Pharmacokinetics Children are not small adults Area is less well researched Rates of absorption in children are faster and peak levels are reached faster (esp. liquids)

4 Proportion of Water in Body through Life

5 Volume of distribution results for the full database (22 substrates). *p < 0.1. Ginsberg G et al. Toxicol. Sci. 2002;66: © 2002 Society of Toxicology

6 Clearance results for the full database (27 substrates). *p < 0.01; **p < Ginsberg G et al. Toxicol. Sci. 2002;66: © 2002 Society of Toxicology

7 Principles of Child Pharmacokinetics II Hepatic metabolism is almost double adult rate in middle childhood and approaches adult rates by 15 years Fat 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 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 When to use Medication

9 Monotherapy is better than polypharmacy Develop a range of familiar drugs Start low and go slow Review frequently Consider use of rating scales Monitor for side effects Monitor for drug/drug interactions Pharmacogenomics: the future? How to use Medication

10 Range of Treatments Anxiolytics Sedatives and Melatonin Antipsychotics Antidepressants: Fluoxetine Mood stabilisers ADHD treatments Mostly unlicensed for children

11 Prescribing to children: Licensed or unlicensed in UK AntipsychoticChild (<12)Adolescent (12-18) ChlorpromazineYes Haloperidol oralYes Haloperidol IMNoYes PimozideNoYes TrifluoperazineYes (anxiety)Yes SulpirideNoYes (>14) Zuclopenthixol IMNo AmisulpirideNoYes(>15) ClozapineNoYes(>16) Olanzapine oralNo Olanzapine IMNo Risperidone oralNoYes(>15) Risperidone IMNo

12 A Antipsychotics Haloperidol and Chlorpromazine have license Unlicensed Olanzepine, Risperidone and Aripiprazole most commonly used in UK practice Wide range of usage: Psychosis Bipolar Tourettes Rapid tranquillisation Mood swings in Borderline Personality Disorder Irritability in ADHD and Autism

13 NICE recommendations Predominantly 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 Personal experience Side effect profile Family history of response Patient or carers preference local expert How to choose

15 Side Effects of Antipsychotics (Bazire 2007) Drug AntiChCardiacEPSELow BPSedationMinor O/D Wt gainProlactinProcon vulsant Aripiprazole -+---?+-- Olanzapine Quetiapine Risperidone --+++?+++- Zotapine ++ + ?+++ Clozapine ? - Amisulpiride ?+ Chlorpromaz Haloperidol ?+

16 Antidepressants Depression in childhood and adolescence has similarities and differences to adulthood Response to medication is different Tricyclics ineffective in Childhood depression SSRI controversy: suicidality and mood lability in early treatment CSM and NICE guidance: Psychological therapies first If 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 Serendipity Given after pneumo- encephalography Children called them their arithmetic pills (Am J Psych 1937)

18 Potential Mechanisms of Action Dopamine- Reuptake inhibition and direct release Methylphenidate Dexamphetamine Dopamine-reuptake inhibitor Modafanil Noradrenaline- Agonists L-amphetamine Noradrenaline- reuptake inhibitor Atomoxetine Alpha 2 adrenergic - agonists Clonidine Guanfacine

19 Stimulants Licensed Methylphenidate Dexamphetamine Unlicensed Amphetamine – L-amphetamine mixed salts (Adderall) Modafanil

20 Features of Stimulant activity Greatest effects on Attention and restlessness Less useful for impulsive behaviours Rapid acting Short half life Clear dose effect relationship Well established side effect profile

21 Dose Response of Methylphenidate on Attention in clinic and classroom (Rappoport et al 1987)

22 Efficacy of the stimulants Responder rate (%)75-90 Methylphenidate 75 Amphetamine70 Normalisation rate (%)50-60 Symptom improvement (%) Behaviour scales30-50 Effect size (SD) Behaviour 0.9 high Attention 0.7medium IQ/ Performance tests0.3low

23 Time of effect Comments Methylphenidate Equasym XL6-8hrsSchool day cover Medikinet Concerta ® XL8-12hrsSleep and appetite Daytrana ® 6-16hrsTransdermal US only Amphetamine compounds Adderall XR6-8hrsImport only Vyvanase12-14hrsProdrug, ltd abuse (lisdexamfetamine)Awaiting UK approval Long Acting Stimulants Stimulant

24 ) Transdermal Methylphenidate (Daytrana) Doses: 10mg, 15mg, 20mg 30mg Applied to hip each morning Stays on after swimming or bathing Irritation rare Suggested use for 9 hours but effects last 3 hours after removal Heal and Pierce CNS drugs (2006)

25 (Vyvanase) Lisdexamfetamine (Vyvanase) Metabolised in GI tract to Lysine and Dexamphetamine Doses: 30mg, 50mg, 70mg Little euphoric effect reducing abuse potential Clin Ther 2007;29:

26 Side Effects Anorexia, weight loss Give with meals Use supplements Dietary advice InsomniaGive earlier Use shorter acting prep Consider melatonin/clonidine ReboundChange to long acting prep Assess timing and overlap DysphoriaConsider comorbidity and treat Change to long acting or alternative stimulant

27 Cardiovascular Risk Sudden death rates in General Population: 0.6-6/100,000 children per year 1/1000 adults per year Estimated sudden death rate on Stimulants: 0.25/100,000 people per year based on Rx data 0.5/100,000 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 outcome Monitor height and weight esp in younger children Some response by week 2 but continue to 6-10 weeks Reduction in irritability precedes core symptom improvements

29 Atomoxetine Niches Treatment resistance, partial response Intolerable side effects Importance of all day cover Possible substance misuse or diversion Comorbid anxiety disorder Tic disorder

30 Atomoxetine Side Effects: - Somnolence, insomnia, nausea, headache, reduced appetite, abdominal discomfort, raised BP and pulse, sexual dysfunction Drug 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 prescriptions - 1 further suspected case in 3.4 million prescriptions Implications: Discuss rare event not routine LFTs Known increase in mood lability in 3% Possible slight increase in suicidal ideation % Atomoxetine v 0% Placebo - One suicide attempt/1357 studied

32 Clonidine Used for ADHD therapy and night sedation Better for restlessness than attention Useful but popularity waning due to side fx Good for tics and comorbid ADHD Doses 0.05 mg-0.2 mg tds Evening rebound Patch available but import only Care with joint prescribing (ECG recommended) Look out for sedation, hypotension, depression, constipation and dry mouth

33 Clonidine controversy Clonidine and Methylphenidate 3 case reports of sudden death FDA review decided no causal link Other relevant factors in all cases Clonidine 4 case reports of cardiac arrythmias, one with congenital malformation Use 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 adults 1 open label study and one RCT show efficacy: Scahill et al JAACAP 2001 Spencer et al JAACAP 2009 Similar to clonidine but less sedating, more headaches and insomnia ? Better for attention than hyperactivity Recent licence in US

35 Conclusions Variations in child pharmacokinetics can lead to less predictable responses Requirement of closer monitoring and shared care with parents Many adult approved drugs are given off licence to children Medications have a restricted but important part in holistic care plan Medications are often given symptomatically rather than for diagnosis


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