Prescribing for Adolescents

1. Prescribing for Adolescents

2. Significant Psychosis**** Hyperactivity OCD Depression**** Tourettes/Tics Rare or not at all MR Autism Conduct Disorder Eating Disorders Sleep Disorder Anxiety Disorder Enuresis Scope – when is psychotropic drug treatment significant for children and adolescents?

3. Key issues in Adolescence for Mental Health Services • Developmental issues • Physical development : puberty • Thinking and reasoning • Self and identity • Relations with family : transition & autonomy • Sexuality • Friendship and peer groups • Education, training and work • Anti-social and offending behaviour • Stress, coping and adjustment • Culture and ethnicity

4. Limits on Child & Adolescent Psychopharmacolgy • Limited evidence base • Few RCTs • Reliance on downward extrapolation from adult studies • Developmental and pharmacodynamic differences child/adult • Off-label prescribing [USA 80%, Jensen 1999]

5. Strategy for optimal psychopharmacological treatment of adolescents [The Big 8] • Clear psychiatric diagnosis • Identification and measurement of those features that are the target of treatment • Treatment “contract” with the patient (and when appropriate, the family] • Good knowledge about various treatment options and their relative risks and benefits • Factors that can influence treatment: • psychological, family, social, and economic • Useful methodology for determining efficacy and optimization of treatment • A constructively critical attitude about models of patho-etiology and how they relate to treatment. • Knowledge of and proficiency in a model of therapeutics that can allow for the implementation and integration of various useful treatments

6. The school or work and social environment • Academic/work history • Peer relationships • Self-management/independent living skills • Contact school/college [with consent] • Reports etc

7. Specific child & adolescent issues • Consent and capacity • MHA 1983 & Children Act 1989 • Gillick competence • Refusal of treatment by competent child • Child protection • Duty to protect • Violence and sexual aggression :in-patient units

8. Baseline Assessment: General Issues • Patient and his or her symptoms • Psychiatric history • Mental State Examination • Measure specific symptoms that are focus of treatment • Medical Assessment including baseline assessment of symptoms which may later feature as adverse side effects

9. The patient’s family or living unit • Family roles • Family psychiatric history • Response to previous treatments • Value systems and attitude to mental health issues and medication

10. Practice points on family interviewing • Younger adolescents best seen with parents, then alone • Older adolescents need the choice • Depressed/anxious parents over-report child behaviour • Parents are less aware of mood states in their children • Crisis management/emergencies may require serial interviews and/or telephone contacts

11. Adolescent onset schizophrenia (13-19 years of age) • 50 times less often before age 15 years than after it (Beitchrnan, 1985). • Average of first onset [EPPIC] 19 years • Insidious onsets more common • Long term Social outcomes are still very poor [Hollis 2000]

12. Atypical Antipsychotics • Risperidone, Olanzepine, Quetiapine, Clozapine, Amisulpiride, • Standard antipsychotic choice for children & adolescents (70-80%o) • very limited evidence-base in younger patients (1 RCT:Kumra et al 1996) • possible increased efficacy against negative symptoms, cognitive impairment • Variable profile of side effects, reduced EPSE

13. Side-Effects of Antipsychotics Can be more severe in children/ adolescents than adults and include: • Dystonias/ EPSE/TD • Increased appetite and weight gain • Type II diabetes & lipid changes • Blood dyscrasias (neutropenia/ agranulocytosis) • Cardiac arrhythmias, inc. QTc interval • elevated prolactin -> reduced estrogen,osteoporosis • Seizures

14. Side Effect Profiles

15. EPSE BY AGE

16. Weight Gain in Adolescents Olanzepine vs. Risperidone vs. Haloperidol Mean age 17 years mean dosage: Olanzepine 12.7mg. Risperidone 3.2mg. Haloperidol 7.6mg

17. Drug Initiation • Start Low, Go Slow • Risperidone 0.5mgs • Olanzapine 2.5mgs nocte • Clozapine 12.5mgs [50mgs/2days] • Increase every 3 to 5 days • Most side-effects occur early (first 4-6 weeks) • Add benzodiazepine (e.g lorazepam 1-2 mg, diazepam 2-5mgs, Clonazepam 0.5-2mgs) for arousal/ agitation • Severe violence/agitation may need RT protocol

18. Atypicals: Target Dose Ranges mgs • Risperidone 2-6 • Olanzepine 2.5-20 • Quetiapine 150-600/750 b.d. • Amisulpiride 400-1200 • Clozapine 300-600 Clozapine plasma level >350ng/ml (0.35mg/L))

19. Switch to Clozapine • Review diagnosis and treatment compliance • Consider lithium if marked affective component • Consider Shot antipsychotic if compliance poor • Switch to clozapine: titrate to optimal dose. • Control for plasma levels and side effects, Continue for 3 – 6 months not effective or not tolerated

20. If Clozapine does not work • Review diagnosis and treatment compliance; withdraw all ineffective medication; give previous most effective drug lowest effective dose; or • Consider another atypical or depot antipsychotic; • re-consider cognitive behavioural intervention

21. summary • Schizophrenia in children and adolescents requires early detection and intervention. • atypicals are first line Tx • side Effect profiles mainly determine choice • share information and decisions with patient and family • interpretation of [NICE] time scales is not clear for >18 • is early use of Clozapine justified?

22. Depression (1975), Marion Patrick (1940-1993) ‘A child endures or enjoys overwhelming misery or overwhelming happiness because he isolates the moment and does not connect it with the future or the past. In my work I try to convey this isolation’.

23. Antidepressants for <l8’sPosition up to June 2003 • TCA’s: in RCT’s, lack efficacy; risky side-effects, e.g. cardiac • MAOI’s: no RCTs; high toxicity • SSRIs: Until 2003, considered relatively safe; • Fluoxetine and Paroxetine efficacious in RCT’s; many open label trials; ‘TREATMENT OF CHOICE’ • Nefazodone (NASSA), Venlafaxine (SNRI), some studies (inconclusive)

24. Antidepressants in ~18’s – current position :Jan. 2004 Licensed use • US: Fluoxetine for OCD [>7yrs+ ] and depression [>8yrs] • Sertraline for OCD [>6yrs) • Paroxetine and Venlafaxine contraindicated: new data show unfavourable balance of risks [esp. re suicidality] vs benefits. • Fluvoxamine may be used for OCD • Expert Working Group Looking urgently at wider safety issues re SSRl’s in paediatric population

25. CBT for depressed children and adolescents – does it work? • NOT for severely depressed adolescents [Harrington 1998] • Treatment of choice for mild/moderate depression, high rates of recurrence. • IPT - promising, only one RCT

26. Prognosis – the transition to adulthood • Most will recover from their depressive Episode • However, high rate of recurrence Predicted by severe presentation and Absence of conduct disorder • Rapid cycling mood overlaps with Emotionally Unstabel PD • Dysthymia often confused with depressive Episodes • Small number develop Bipolar Disorder Small number go on to kill themselves