;; Psychopharmacology of Adolescent Addiction & Co-Morbid Psychiatric Disorders.

1. ;;Psychopharmacology of Adolescent Addiction & Co-Morbid Psychiatric Disorders. Dr. Patricia Byrne.

2. Lecture Overview • Part 1 Substitution and Detoxification of Adolescent Addiction  • Part 2 Managing Co-morbid Psychiatric Disorders.

3. Drugs of Abuse • Opiates – Heroin, Morphine, Codeine, Methadone. • Cocaine, ‘Crack’ cocaine. • Amphetamines – Esctasy, Speed. • Hallucinogens – LSD, Magic Mushrooms. • Benzodiazepines. • Sedative medications – hypnotics, antidepressants, antipsychotics. • Cannabis. • Alcohol.

4. Opiates • Heroin - ‘gear’, ‘smack’, ‘junk’. • Smoked ‘chasing’, skin popped or intravenous use ‘banging’. • Sold in ‘bags’ or else by weight ‘an 1/8th(oz)’ Ireland a bag size of pea costs €20 ‘a score’. • Use can range from ½ bag to 7-9 bags a day. • Purity and size of bags differ!!! ‘in Scotland the bags were twice as big and three times as strong..’ & ‘I had to inject in the UK as the stuff wasn’t as good.’

5. Treatment of Opiate Abuse in Adolescents. • History, M.S.E, Physical exam including dentition, Inv. – FBC, LFT, U&E, Viral screen. • Confirm dependence. – 3 urines at 3-4 day intervals. 6-AM * is a specific metabolite present for about 12 hours after heroin use. • Assess motivation –young person or others? • Assess supports. • Treatment plan – biopsychosocial. * 6 - acetyl morphine

6. Substitution • Replacing heroin with an alternative agent, aiming for harm reduction. • Substitution strategies • Methadone – opiate agonist. • Buprenorphine – partial opiate agonist. • Heroin – some evidence for adults who fail optimal MMT > 6 months. • Psychosocial treatments add benefit to opiate replacement, but are not effective on their own. • Naltrexone (opiate antagonist) first requires detoxification from opiates.

7. Methadone Maintenance Treatment (MMT) in Adolescents • In Adults • MMT improves health and reduces illicit heroin use, infectious diseases transmission and overdose death (1). • MMT doses 60-100mg/day are more effective in retaining patients and reducing heroin and cocaine use during treatment (2) (in an opiatedependant population). • Licencing – UK ‘adults’, Ireland 18 +, US 18+ • Limits evidence base in adolescents – used with caution on basis of clear benefit in adults.

8. MMT in Adolescents • ‘Full’ opiate agonist, low lethal dose, highly dependence forming, long half life. • Changes in a persons tolerance for opiates occur when commencing treatment, increasing or decreasing doses. • This must be explained as the risk of overdose is increased at these times. • If a person missed 2 or more days of MMT their tolerance may have reduced and even a stable dose must be reviewed and reduced.

9. MMT in Adolescents • Full informed consent, ensuring they are able to explain back the risk of overdose. Consent from parent / legal gaurdian. • Beware over-reporting of opiate use, polysubstance misuse, co-morbid alcohol or benzodiazepine abuse. • Once daily supervised dose, green syrup 1mg/1ml. Y.P.P. twice weekly supervised urine samples. • Dose - titrate according to signs and symptoms of opiate withdrawal. Start low e.g. 20 mg & go slow, max increase 10mg a day.

10. Buprenorphine • Licence - UK 16 +years, Ireland >15 years under specialist supervision only. • Sublingual tablet – may take 10-15 minutes to dissolve. • Partial agonist at m receptor, high affinity and slow release. Antagonist for k - reduces withdrawal symptoms. Eases detoxification? • Partial agonist – improves safety compared to methadone, but may not be suitable for those requiring higher replacement levels (=> 40mg methadone)

11. ‘Precipiated Withdrawal’ • High affinity – buprenorphine will bind preferentially to opiate receptors over methadone or heroin, displacing them from the receptors. • Partial agonist – lower intrinsic activity at the opiate receptor than heroin or methadone. • If someone takes their first dose of buprenorphine and they are still under the influence of opiates, buprenorphine will displace the opiate and bind to the receptor. • This will result in a sudden drop in activity at the opiate receptor, inducing withdrawal symptoms after 20-30 minutes.

12. Precipiatated Withdrawal • A person commencing buprenorphine must understand this concept, and should not have the first dose of buprenorphine within 12-18 hours of last heroin use, or within 24 hours of last methadone use. • Ideally the person should present in the early stages of withdrawal, and be supervised for 1 hour after the first trial dose of 2 mg, after which a second dose of 2 mg can be administered.

13. Buprenorhine • Once stabilized on buprenorphine a person will experience reduced effect of illicit opiate use as receptors are already bound by buprenorphine. • Half life increases with dose. • Low dose (2-4 mg) T ½ 12 hours, high dose (16-32 mg) T ½ 48-72 hours. At higher doses can be administered every 2 - 3 days (max 36mg at one time). • Diversion and IV use in Australia & France. Awaiting Buprenorphine / Naloxone preparation.

14. Buprenorphine vs Methadone • Bell compared treatment retention in adolescents with buprenorphine or methadone – MMT appears more effective at preventing premature drop out (3). • Consider opiate tolerance, duration of dependence, oral or IV drug use, ability to present close to or in withdrawal.

15. Detoxification Withdrawal strategies • Tapered opioid agonist reduction -Methadone / Buprenorphine. • Adrenergic agonists - Clonidine, Lofexidine. Reduces withdrawal symptoms via non opioid mechanisms. • Opioid antagonist - Naltrexone + adrenergic agonist (minimal sedation). 4. Opioid antagonist plus heavy sedation/anesthesia – RRx3 of complications (4).

16. Detoxification • RCT comparing clonidine with buprenorphine. 36 adolescents, 13-18 years, 28 day detox. (5). • Counselling 3 times weekly, contingency management, all offered treatment with naltrexone following withdrawal. • Retention – 72% bup. vs. 39% clon. • Opiate neg. urines – 64% bup. vs. 32% clon. • HIV risk behaviour –decreased in both groups (self-report). • Naltrexone started – 61% bup. vs. 5% clon.

17. Cocaine • Rapid intoxication, withdrawal effects include depressed mood, lethargy, irritability, anorexia, disturbed sleep pattern, craving. • Acute use – increases dopamine, serotonin and noradrenaline levels by blocking reuptake inhibitors. • Chronic use leads to depletion of dopamine, and down-regulation of monoamine system. • Treatments complicated by high drop out rates. Dopamine agonists, Carbamazepine, & Antidepressants all tried, no evidence of benefit (6). YPP use MI / CBT, linked to contingency management system.

18. Amphetamines • Includes amphetamines ‘Speed’ and Ecstasy. ESPAD 2003 survey of 16 year olds: lifetime use - < 1% amphetamines, 5-8 % Esctasy. • Cohrane review - Fluoxetine – Short term reduced craving, no effect on use. No bio/psycho/social treatment has found to be effective (7). • Withdrawal – common >80%, intense craving. No studies to guide treatment (8). • Psychosis - antipsychotic medications can reduce agitation (9). Treat as psychosis.

19. Benzodiazepines • ‘Sleepers, downers, blueys, roche’. • Often early onset of abuse. Frequently polysubstance misuse. • Quantity and type can be measured on urine samples. • YPP links to contingency management, MI, education regarding effects of reducing dose. • Prescribed detoxification in community is difficult as easy availability leads to ongoing illicit use. If motivated may detox themselves. • Inpatient detoxification rarely required, carbamazepine useful adjunct (10).

20. Zzzzz drugs… • Drugs that have sedative properties are open to abuse – zopiclone, zolpidem & zotepine. • Sedative antidepressants – e.g. mirtazepine (zipsin), dothiepin (prothiaden) reports of abuse in MMT population. • Sedative antipsychotics – e.g. olanzapine, chlorpromazine.

21. Cannabis • Hash, blow, weed, skunk … • Smoked or ingested. • Most commonly used illicit drug among adolescents – ESPAD 2003 survey 16 yr olds, lifetime use 38-40% in RoI and U.K., 20% use in previous 30 days. • Differing strengths ‘skunk’ or ‘hydro’ have much higher levels of THC. • Early onset use, low percieved harm. • Serious mental health risks – amotivational syndrome, RRx2 psychosis, increased with heavier use and earlier age use (11).

22. Cannabis • No pharmacological treatment options. • Cochrane Review psychological therapy • CBT individual & group. • Brief individual Motivational Interviewing (MI). • Outcome • Brief MI effective in reducing use. • Extended (9+ sessions) ind. CBT > brief ind. MI. • Contingency management (token economy) may improve outcomes in both groups. (12) • YPP Psycho-education, MI, Contingency Management.

23. Alcohol • Alcohol major role in society and peer group interactions. Patterns of drinking often binge rather than daily dependence.

24. Alcohol • Non confrontaional approach, explore alternative options for adolescents. • MI useful in allowing adolescent to explore effects of alcohol and become motivated for chnge. • CBT approaches can be used to recognise high risk situations, problem solve and form an individual relapse prevention plan.

25. Alcohol Treatments • In adults AA, 12 step facilitation (TSF) and psychosocial treatments all benefit (13). • Adolescents – may be useful, concerns re identity as an ‘addict’. • If inpatient stabilization and detoxification required, benzodiazepines +/- carbamezepine Need plan of psychosocial support for discharge. • Relapse prevention • Acamprosate – no evidence for adolescent use. • Disulfiram – only 2 case reports in adolescents, 1st abstinent x 4/12, 2nd non-compliant (14). Requires high motivation, understanding of adverse effects if drinks – greatly limits use.

26. Co-morbid Pyschiatric Disorders • Estimated that 2/3rds of adolescents with Substance Use Disorders (SUD) have co-morbid psychiatratric disorder(s). • Increasingly adolescents who present to CAMHS also use/misuse substances. • Direction of causality - substance use to self-medicate distressing symptoms, or psychiatric symptoms as a result of substance misuse. Often unclear. • Major co-morbid disorders are ADHD, Conduct Disorder, Anxiety Disorders, Mood Disorders and Psychosis.

27. Treatment Dilemmas • Do we treat SUD or Psychiatric D/O, or both? • Where do we treat – CAMHS or specialist adolsecent addiction service? • How do we treat? Limited studies on co-morbid population -> combine evidence for each disorder to form an individual plan. • Pharmacological options limited in adolescents. • Adolescents who substance misuse tend to require even higher levels of social and motivational support to engage with pharmacological and psychological treatments.

28. ADHD & Conduct Disorder • ADHD increases the risk of SUD X 2 (15). • ADHD/Conduct disorder increases this risk even further – need to diagnose and treat ADHD optimally to prevent complications. • Study showed improvement in SUD and ADHD symptoms in adolescents and young adults treated with Methylphenidate (16), and also study showed improvement in adults with childhood onsetADHD and SUD (17).

29. Anxiety Disorders • Most common disorder in adolescence. Substance misuse may be a strong avoiding & reinforcing strategy to self-treat social phobia, GAD, and PTSD. If not recognised outcome for both disorders reduced. • Anxiety disorders often present with co-morbid depressive symptoms or disorders. • Consider psychological treatment (MI followed by CBT), treat SUD as appropriate. • If these measures fail, consider fluoxetine with caution. Avoid paroxetine, venlafaxine & sedative agents, and monitor for emergent suicidality.

30. Depressive Disorder • Diagnosis complicated by SUD – ‘primary’ or ‘secondary’. Depression may also increase the severity of SUD. • Ability to engage in CBT reduced by substance misuse, ability to engage in treatment for SUD reduced by low mood. • Study of adolescent inpatients on a dual diagnosis unit - 31% MDD, those with ‘secondary depression’ did not remit with abstinence (18). • Fluoxetine has been shown to reduce depressive symptoms and SUD in substance abusing adolescents. 3 year follow up suggests worse outcome for MDD than SUD (19).

31. BPAD • Very difficult to diagnose in adolescents, especially if abusing stimulant drugs. • Age of onset important – US studies youths with adolescent onset BPAD had 8.8 times the risk of SUD compared to youths with Child Onset BPAD (20). • Mood stabilizer response rates in adolescents Valproate 53%, lithium 38%, carbamazepine 38% (21). • Co-morbid SUD & BPAD – Geller showed improved overall functioning and reduced SU in double blind placebo study of lithium (22).

32. Psychosis • Early onset schizophrenia outcome poor. SUD worsens short and long term outcome. • Major concern is evidence of RR X 2 of developing psychosis associated with early onset cannabis use (11). • Treatment complicated as lack of insight and amotivation is a feature of both disorders. • Treat psychosis, during periods of remission psycho-educate re SUD, use psychological and pharmacological disorders as appropriate.

33. SUD & Psychiatric Co-morbidity, a summary… • Always be open to dual diagnosis, use careful history taking to understand the interaction between the disorders from the clinical view and the adolescent’s view. • Support the adolescent in becoming motivated to engage in treatment. • Parallel treatment often required, intense pyschosocial support always required.

34. Recommended reading and references are included in your delegate pack. • Thank you.