www.mghcme.org Adolescent Substance Abuse Timothy E. Wilens, M.D. Chief, Division of Child & Adolescent Psychiatry, (Co) Director of Center for Addiction Medicine, Massachusetts General Hospital Massachusetts General Hospital for Children Harvard Medical School
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Adolescent Substance Abuse Timothy E. Wilens, M.D.
Chief, Division of Child & Adolescent Psychiatry,
(Co) Director of Center for Addiction Medicine,
Massachusetts General Hospital
Massachusetts General Hospital for Children
Harvard Medical School
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Disclosures
• Grant Support and Consultant: NIH, NIDA
• Consultant: Euthymics/Neurovance, Ironshore, Sunovion, TRIS, US National Football League ERM Associates, U.S. Minor/Major League Baseball, Bay Cove Human Services Clinical Services and Phoenix House
• (Co/edited) books: Guilford Press, Cambridge Press, Elsevier: Straight Talk About Psychiatric Medications for Kids (Guilford Press), ADHD in Children and Adults (Cambridge Press), and Massachusetts General Hospital Comprehensive Clinical Psychiatry (Elsevier)/ Psychopharmacology & Neurotherapeutics (Elsevier) .
• Licensing Agreement: Dr. Wilens is co/owner of a copyrighted diagnostic questionnaire Before School Functioning Questionnaire (BFSQ). Dr. Wilens has a licensing agreement with Ironshore BSFQ Questionnaire.
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Learning Objectives
• Understand the onset of substane use disorders (SUD) in adolescence and young adulthood.
• Learn the major psychiatric disorders associated with SUD in adolescents
• Learn effective treatments for core SUD related symptoms and common comorbidities in adolescent SUD
• Discuss risk management considerations in the care of adolescents with substance use disorders (SUD)
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0
5
10
15
Alcoholabuse/dependence
Drugabuse/dependence
Any substance usedisorder
Merikangas et al. J.Am.Acad.Child Adolesc.Psychiatry, 2010;49(10):980-989
Lifetime Prevalence of DSM-IV Substance Use
Disorders Disorders in the National Comorbidity
Survey-Adolescent (NCS-A)
• Psychotherapeutics: Prescription-type pain relievers, tranquilizers, stimulants, and sedatives
• Illicit drugs include Marijuana/hashish, cocaine (including crack), heroin, hallucinogens, inhalants, or
prescription-type psychotherapeutics used non-medically.
Results from the 2012 National survey on Drug use and Health
Figure 2.2 Past Month Use of Selected Illicit Drugs among Persons Aged 12 or Older:
2002-2012
Johnston, L. D., O'Malley, P. M., Bachman, J. G. & Schulenberg, J. E. (December 11, 2007). "Overall, illicit drug use by American teens continues gradual decline in 2007." University of Michigan News Service: Ann Arbor, MI.
Johnston, L. D., O'Malley, P. M., Bachman, J. G. & Schulenberg, J. E. (December 11, 2007). "Overall, illicit drug use by American teens continues gradual decline in 2007." University of Michigan News Service: Ann Arbor, MI.
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56%
8%
18%4%9%
5%
Free from a Friend or Relative
Taken from a friend or relative without asking
Bought from a friend or relative
Drug dealer
From one doctor
Other source
SAMHSA, 2008 National Survey on Drug Use and Health (September 2009)
70%
From
friends
and
family
family
Sources of Pain Relievers for Most Recent
Nonmedical Use Among Past Users
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Rates of Substance Use Disorders (SUD) in Boston
College Students who Misuse Stimulants
(Wilens et al. J Clin Psych (2016) in press)
Misusers
Controls
Substance Use Disorders
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Risks of Untreated SUD: Mortality
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0
50
100
150
200
250
300
350
400
30 35 54
116
143
253
400 T
ota
l C
aff
ein
e in
mg
's p
er
12
ou
nce
s
Caffeine Content of Energy Drinks available in the
United States
Reissig C.J. et al. Drug Alcohol Depend. 2009; 99:1-10
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Age at Onset of DSM-IV Drug
Abuse and Dependence
Compton et al. Arch Gen Psychiatry/ Vol 64, May 2007; 45(11): 1294 - 1303
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Juvenile SUD: Overview
• Definitions
– Use - at least once [often stratified in reports as past 30d, past year]
– Misuse - emergence of pattern of use
– Substance Use Disorder (DSM V) - pattern of misuse with impairment and/or consequences, inability to control use, use despite consequences, physiological symptoms
• Graded mild-severe
• No differentiation between abuse vs dependence
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Photo courtesy of the NIDA Web site. From
A Slide Teaching Packet: The Brain and the
Actions of Cocaine, Opiates, and Marijuana.
Inhibitions
Major Brain Circuits Involved in Addiction
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Substance Mechanism of Action
Alcohol GABA, opioid agonist; NMDA antagonist
Cocaine Blocks re-uptake of dopamine
Amphetamines Stimulate dopamine release
PCP, ketamine NMDA antagonist
Opioids Mu, delta, and kappa agonism
Cannabis CB1 agonist
MDMA (“ecstasy”) 5HT release and re-uptake inhibition; mild DA and NE reuptake inhibition
LSD (“Acid”) 5HT2a agonism leading to increased glutamate?
(Adapted from Textbook of SUD Tx: Galanter; APA Press 2013)
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Juvenile SUD: Risk and Protective Factors
Familial - runs in families
– Higher rates of SUD in children in SUD families
• 2-4 fold elevated risk for SUD in offspring
– Exposure to parental SUD influences child SUD
– Higher rates of psychopathology and dysfunction in the children of SUD parents
(Wilens et al., 2000; 2002, 2005, 2013; Nunes et al. 2003; Rhee et al. 2003; Yule et al. AJA 2013)
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Juvenile SUD: Risk and Protective Factors
Genetic - vulnerabilities for inherited subtypes
– Genetics account for ca. 50% of risk
– Early onset (adolescent) SUD associated with heredity (55% m-73% f)
• Associated with conduct, mood, ADHD
• Sons of male alcoholics at up to 9 fold risk for SUD
Kendler et al. Am J Psych online: 2014
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Juvenile SUD: Risk and Protective Factors
Environmental exposure (availability, values, modeling/conventionality)
– Family exposure
– Peer use
– School exposure
– Community SUD
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Juvenile SUD: Risk and Protective Factors
Self esteem issues
• Poor self esteem or image linked to later SUD
• Poor ego development linked to SUD
• SUD exacerbates self esteem issues
(Khantzian et al. Am J Add, 2012)
Dynamic issues • Self-medication - amelioration of specific symptoms • Affect tolerance - use of substance to blunt affect states • Familial Patterns and modeling
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Juvenile SUD: Overlap with Psychopathology
Rates of Adolescent Psychopathology
0
20
40
60
80
100
(-) SA (+) SA
(Costello et al., 1998; Buckstein 1989; Kandel, 1996; Weinberg, 1999:Kramer et al., 2003; Tims et al., 2003)
Rate (%)
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Common Psychopathology in Adol SUD
• Conduct Disorder
– High risk for SUD (80-90%)
– Examine for comorbid mood
• ADHD
– 2 fold risk for SUD
– 50% of adol SUD with ADHD
– Treatment reduces SUD
• Anxiety/PTSD
– 2 fold risk for SUD
– Anxiety frequent “cue” for substance use
– PTSD precedes, or is result of SUD
• Depression
– 2 fold risk for SUD (precedes SUD)
(Wilens et al., JAACAP 2011; Husson Psych Add Behav 2011; Clarke et al 2004; Riggs et al 2007)
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Life
tim
e P
reva
len
ce
Persistent BPD vs. Control: p=0.001;
Persistent BPD vs. Non-Persistent BPD: p=0.2;
Non-Persistent BPD vs. Controls: p=0.2
Development of SUD in Adolescent Bipolar Disorder
Wilens et al. Presented at AACAP 2012
Bipolar
Control
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Juvenile SUD: Diagnostics
– Evaluate medical condition including complications (LFT, STDs)
– Generate differential diagnosis for psychiatric/medical symptoms
– Utilize urine, saliva, or hair toxicology screens
(Gignac, Wilens & Waxmonsky and Wilens, Adol Substance
Abuse, in Child Adoles Psychopharm 2010)
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Recent “Synthetic” Drugs of Abuse
Bath Salts • Methyleneduioxypyrovalerone (MDPV) • Stimulant-like euphoria of 6-8 hrs (PO, smoke, IV) • Stimulant like effects: tachycardia, hypertension, arrthymias,
hyperthermia, sweating, seizures • Panic attacks, anxiety, agitation, paranoia, psychosis • Not detected by routine drug screens
Synthetic Marijuana (Spice, K2, Herbal incense) • Cannabis-like high • Chemicals sprayed on herbs • As of March 2011-many components are schedule 1 Controlled substance
act (illegal) • Reactions: agitation, convulsions/seizures, psychosis, withdrawal states
after persistent use • Not detected by routine drug screens (does NOT result in positive
cannabis)
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Screening Adolescents for Drugs and Alcohol
• During past 12 months did you
A) Drink any alcohol
B) Smoke any marijuana or hashish
C) Use anything else to get high?
• If NO: Ask if you have ever ridden in a CAR driven by someone who was high or had been using drugs or alcohol
• If YES-complete CRAFFT (next page)
(Knight et al., Arch Pediatr Adolesc Med 1999: 153: 591-6)
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Screening Adolescents for Drugs and Alcohol
C Have you ever ridden in a CAR driven by someone who was “high” or had been using alcohol or drugs?
R Do you ever use alcohol or drugs to RELAX, feel better about yourself, or fit in?
A Do you ever use alcohol or drugs while you are by yourself, ALONE? F Do you ever FORGET thins you did while using alcohol or drugs? F Do your family or FRIENDS ever tell you that you should cut down on
your drinking or drug use/ T Have you ever gotten into TROUBLE while you were using alcohol or
drugs?
• Two or more yes answers on the CRAFFT suggest a serious problem and a need for further assessment
(Knight et al., Arch Pediatr Adolesc Med 1999: 153: 591-6)
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According to Group Health’s standards for substance use disorder
documentation, clinical staff may and should document the following
information related to substance use:
• Patient disclosures about substance use, abuse, or dependence.
• Patient disclosures about current or past chemical dependency
treatment.
• Completed screening tools including:
- Adolescent substance use screening tool (CRAFFT) and CRAFFT
results.
- Others
- A DSM diagnosis of substance abuse or dependence and the pertinent
clinical information that supports the diagnosis.
- Referrals for a chemical dependency evaluation (includes all levels of
care, behavioral, medical, inpatient, partial, outpatient).
Protection of chemical dependency information begins at the start of a
treatment program, not at the time of screening, identification, or referral
(as outlined in confidentiality regulation 42 CFR Part 2).
Adapted from Group Health Guidelines
www.ghc.org/all-sites/guidelines/drug-adolescent.pdf
Documentation
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Juvenile SUD: Treatment
Stabilization of alcohol / drug abuse
– Harm Reduction: Lowering use
– Absolute sobriety: None
– Basic self-help philosophy
• Give multiple referrals
• Alcoholics Anonymous/Narcotics Anonymous for teens
• Rational Recovery
• Avoid “tough love” as initial step
(Gignac, Wilens & Waxmonsky and Wilens, Adol Substance Abuse, in Child Adoles Psychopharm 2010)
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Juvenile SUD: Treatment
Psychotherapy – Groups: for youth and for their parents – Motivational interviewing
• Engage/collaborative connection with patient • Discuss issues that are problematic (don’t focus on SUD)
– Cognitive Behavioral modification • Reduction in impairing behaviors • Reduce SUD “cues”
– Individual -"Recovery Sensitive Therapist" • Coping skills (esp. for conduct disorder) • Cognitive/ behavioral Tx • Relapse prevention (eg reducing cues, balance in life)
(Wilens, McKowen & Kane Contemp Peds 2013)
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Psychopharmacologic Strategies with Juvenile Substance Abuse
• Aversive treatment (antimetabolism)
• Reduce urge or craving
• Substitution therapy
• Treat underlying psychiatric comorbidity
• Preventive therapy
(Gignac et al. 2010; Yule and Wilens, Curr Psych. 2015; 14(4): 36-39, 47-51.)
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Pharmacotherapies to Reduce Urge or Cravings
• Nicotine – Nicotine patch, inhaled nicotine, nicotine gum,
nicotine lozenges – Bupropion (Wellbutrin, Zyban) – Varenicline (nicotinic modulator) – Cytisine (acacia seed extract, nicotinic partial
agonist)-used in Europe – Experimental: Riminobant (Cannabinoid type I
receptor antagonist); nicotinic partial/full agonists-various nicotinic subunits
– Role of e-cigs questionable (e.g. may encourage cig use)
(Lerman et al. J Clin Oncol 2005:23-311-323; Basil et al. Psychiatry 12:2005:49-52; West et al.
NEJM 2011:365: 1193-200; Dutra and Glants, JAMA Pediatrics, 2014: 168: 610-617).
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Pharmacotherapies to Reduce Urge or Cravings
• Alcohol – Naltrexone (Rivea) -reduces alcoholic drinking: dosing 25-50 mg
BID to TID – Acamprosate (Campral) -helps with abstinence: dosing 333 mg 1-
2 TID – Topirimate (Topamax) -helps reduce alcoholic drinking, maintain
abstinence: dosing <300 mg /day – Odansetron (Zofran) -helps reduce urges and drinking in early
onset alcohol use disorders; 2-8 mg/day – Baclofen -GABA derivative, anecdotally reported to reduce
drinking urges and edginess; 10-20 mg/day – Dilsufiram (Antabuse)- reaction to alcohol (use for passes, highly
motivated youth); blocks aldehyde dehydrogenase
(Lerman et al. J Clin Oncol 2005:23-311-323; Basil et al. Psychiatry 12:2005:49-52; Johnson et al. JAMA 2007; 298:1641-
1651; Niederhofer &Staffen: Eur Child Adolesc Psychiatry:12:144148 2003; Deas D. et al., JAACAP 2005. 15:723-728; ADD
RECENT REFERENCE)
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Pharmacotherapy for Marijuana Use Disorders
• N-Acetyl Cysteine (NAC)-natraceutical-dosing 1200 mg BID (RCT; Grey et al. Am J Psych 2012)
• Buspirone (pilot RCT; McRae-Clark et al., 2009)
• Lofexidine/Dronabinol (Haney et al., 2008)
• Gabapentin (pilot RCT; Mason et al., 2012)
• Topirimate (adult addiction studies)
• Rimonabant- experimental (CB-1 receptor blocker; EU approval and withdrawal: mood/SI) (Huestis MA, et al.
Psychopharm 2007)
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Pharmacotherapies to Reduce Urge or Cravings
• Heroin, Opiates (Oxycontin)
– Naltrexone (oral: Rivea, intramuscular: Vivitrol) • Approved in adults; used off label in adolescents
– Buprenorphine (Subutex; Suboxone [buprenorphine+naloxone]) • Approved for individuals > 16 years
• Qualified physician
– Methadone • Approved for individuals > 18 years
• Administered via clinics
(Welsh & Meltzer, Psychiatry 2005 12: 29-39; Kaumpman K, Psychiatry 2005 12:44-48;
Marsch et al. Arch Gen Psych 2005; Woody et al. JAMA 2008)
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ADHD and SUD: Pharmacotherapy
Antidepressants/Noradrenergic agents Atomoxetine Bupropion Arousal agents Modafinil Stimulants (use extended release) Methylphenidate Amphetamine compounds
Wilens T, Morrison N. Current Opinion in Psychiatry. 2011. 24:280–285
www.mghcme.org Levin et al. JAMA Psychiatry. 2015;72(6):593-602.
Higher Dose Mixed Amphetamine Salts XR in
Helpful in ADHD & Cocaine Use Disorder (N=126)
%
13 week Randomized Controlled Trial
Diagnosis: Cocaine Use Disorder and ADHD
Treatment: CBT +/- MAS XR
Atomoxetine Improves Outcome in Recently Abstinent Adults
An event ratio of 0.737 indicates that, relative to patients treated with placebo, atomoxetine-treated
patients experienced an approximately 26.3% greater reduction in the rate of heavy drinking. Separation
between groups first occurred at day 55.
Event ratio = 0.737
P value = .0230
Event ratio = 0.737
P value = .0230
12 week placebo controlled study N = 147 subjects Abstinent from 4-30 days Findings: (ATX vs. placebo) Improved ADHD Scores No differences in relapse rate Improved OCD scores Improved heavy drinking (shown) F-U study: Few side effects with alcohol
(Wilens et al. Drug Alc Dep 2009:96:145-154 2008; Adler et al. Am J Addict 2009:18: 393-401 )
Atomoxetine
Placebo
A RCT of Fluoxetine and Cognitive Behavioral Therapy
in Adolescents with Major Depression and SUD
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60
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75
0 4 8 12 16
Week of Treatment
CD
RS
-R t
Sco
re A
dju
sted
Mea
n (
SE
) Fluoxetine +
CBT
Placebo + CBT
Riggs P. et al. Arch Pediatr Adolesc Med 2007. 161:1-9
N=126 adolescents (13-19 yrs)
FLX dose = 20 mg
P<0.05; effect size 0.78
N=126 adolescents (13-19 yrs)
FLX dose = 20 mg
Depression
5
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15
20
25
30
0 4 8 12 16
Week of TreatmentT
ob
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Su
bst
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ce U
se i
n P
ast
30
Da
ys,
Ad
just
ed
Mea
n (
SE
), d
Fluoxetine +
CBT
Placebo + CBT
Substance Use
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Lithium Improves SUD in Bipolar Adolescents (Geller et al., JAACAP, 1998)
0
10
20
30
40
50
60
3 4 5 6
Substance Use
Weeks
Per
cen
t P
osi
tiv
e U
rin
es
Placebo (N=12)
Lithium (N=13)
Functioning
35
40
45
50
55
60
65
BSL 1 2 3 4 5 6Mea
n C
GA
S S
core
s
Weeks
Lithium (N=13)
Placebo (N=12) p<0.05
p<0.05
•Mean age = 16 yrs
•Alcohol and/or drugs (marijuana)
•Dose: [Lithium] = 0.9 to 1.3 me/L
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Quetiapine plus Topiramate Reduces Cannabis Use in Adolescents with Bipolar Disorder (N = 75 patients aged 12-21
years)
0
2
4
6
8
10
12
14
Baseline End of Study
Quetiapine+placebo
Quetiapine+Topiramate
Quetiapine dosing: 800 mg Topiramate dosing: 75 mg - 150 mg BID BPD YMRS Scores improved with both treatments
-14 Quetiapine + topiramate
-16 Quetiapine + placebo
(Delbello et al. AACAP presentation 2011)
P<0.05
Days used (past month)
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Juvenile SUD
Clinical management guidelines – Frequent communication with parents, therapist,
counselor, or other caregivers
– Clear expectations
– Documentation of clinical course, efforts, risk behaviors
– Monitoring of appropriate adherence with prescription (and other f/u recommendations)
– Frequent follow-up visit
– Involvement of legal system if necessary
(Gignac, Waxmonsky and Wilens, Adol SA, in Child Adoles Psychopharm, 2010
(Gignac et al. 2010; Yule and Wilens, Curr Psych. 2015; 14(4): 36-39, 47-51)
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Juvenile SUD: Confidentiality
• Need to discuss SUD with patient & parent
1) Adolescent discussion with parent
2) Practitioner + adolescent discussion with parent(s)
• Need for immediate disclosure
– Dangerousness or severe SUD (eg. IV)
– Incompetent adolescent
(Gignac, Waxmonsky and Wilens, Adol SA, in Child Adoles Psychopharm, 2010)
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Considerations When Using Medications in High Risk Adolescents or Substance Abusers (1)
• Practitioner ambivalence of using medications
• Ensure diagnosis (e.g. review ancillary data, request return evaluation visit)
• Limit and keep track of pill counts
• Set policy on lost prescriptions or early renewals
• Obtain random urine toxicology screens
Wilens TE. Psychiatr Clin North Am. 2004;27(2):283-301.; Riggs PD, et al. J Am Acad Child Adolesc Psychiatry. 1998;37(3):331-2.; Schubiner H. CNS
Drugs. 2005;19(8):643-55.; Wilson JJ, Levin FR. J Child Adolesc Psychopharmacol. 2005;15: 751-763.; Mariani JJ, Levin FR. Adv Psychiatry. 2006;
Wilens et al. JAACAP 2008; Wilens et al Contemp Peds 2013; Gignac et al. 2010; Yule and Wilens, Curr Psych. 2015; 14(4): 36-39, 47-51).
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Considerations When Using Medications in High Risk Adolescents or Substance Abusers (2)
• Frequent patient visits
• Use of nonstimulants and extended-release stimulant preparations for ADHD; nonbenzodiazepines for anxiety
• Discussion with patient regarding safe storage and not advertising availability of medications
• Discussion of withholding information (e.g. overdoses, use of illicit drugs)
• Discussion of potential ethical and legal complications of misuse and diversion
• Documentation of “discussions”
Wilens TE. Psychiatr Clin North Am. 2004;27(2):283-301.; Riggs PD, et al. J Am Acad Child Adolesc Psychiatry. 1998;37(3):331-2.; Schubiner H. CNS
Drugs. 2005;19(8):643-55.; Wilson JJ, Levin FR. J Child Adolesc Psychopharmacol. 2005;15: 751-763.; Mariani JJ, Levin FR. Adv Psychiatry. 2006;
Wilens et al. JAACAP 2008; Wilens, et al Contemp Peds 2013; (Gignac et al. 2010; Yule and Wilens, Curr Psych. 2015; 14(4): 36-39, 47-51.
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Juvenile SUD: Summary
• Juvenile SUD is commonly comorbid with psychopathology
• Screening, discussion, and documentation constitute components of care of these youth
• Treatment of psych may reduce ultimate SUD
• Treatment of comorbid youth requires both SUD and psych intervention
• Pharmacotherapy can be effective in youth with SUD problems
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