;; Psychopharmacology of Adolescent Addiction

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Psychopharmacology of Adolescent Addiction
Co-Morbid Psychiatric Disorders.

• Dr. Patricia Byrne.

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Lecture Overview

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

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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.

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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 wasnt as
  good.

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Treatment of Opiate Abuse in Adolescents.

• History, M.S.E, Physical exam including
  dentition, Inv. FBC, LFT, UE, 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

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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 gt 6 months.
• Psychosocial treatments add benefit to opiate
  replacement, but are not effective on their own.
• Naltrexone (opiate antagonist) first requires
  detoxification from opiates.

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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 opiate
  dependant population).
• Licencing UK adults, Ireland 18 , US 18
• Limits evidence base in adolescents used with
  caution on basis of clear benefit in adults.

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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.

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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.

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Buprenorphine

• Licence - UK 16 years, Ireland gt15 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 (gt 40mg
  methadone)

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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.

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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.

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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.

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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.

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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).

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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.

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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.

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Amphetamines

• Includes amphetamines Speed and Ecstasy. ESPAD
  2003 survey of 16 year olds lifetime use - lt 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 gt80, intense craving. No
  studies to guide treatment (8).
• Psychosis - antipsychotic medications can reduce
  agitation (9). Treat as psychosis.

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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).

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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.

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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).

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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 gt brief ind. MI.
• Contingency management (token economy) may
  improve outcomes in both groups. (12)
• YPP Psycho-education, MI, Contingency Management.

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Alcohol

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

ESPAD 2003 16 yr olds RoI UK
Lifetime Use 42 47
Binge (gt5 drinks) in last 30 days 31 29
Drunkenness gt 20 times 32 27
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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.

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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.

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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.

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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 -gt 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.

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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 onset ADHD
  and SUD (17).

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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.

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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).

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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).

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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.

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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 adolescents view.
• Support the adolescent in becoming motivated to
  engage in treatment.
• Parallel treatment often required, intense
  pyschosocial support always required.

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