www.mghcme.org

Adolescent Substance Use and Use Disorders

Timothy E. Wilens, M.D.

Chief, Division of Child & Adolescent Psychiatry, (Co) Director of Center for Addiction Medicine,Massachusetts General HospitalMassachusetts General Hospital for ChildrenHarvard Medical School

www.mghcme.org

Faculty Disclosure

. Timothy Wilens, M.D. Grant support (Research): NIH (NIDA)Consulting Fees: Alcobra, Neurovance/Otsuka, Ironshore, and KemPharmRoyalties (Published author/ co-editor/co-owner ofcopyrighted diagnostic questionnaire, licensing agreement): Guilford Press, Cambridge University Press, Elsevier, IronshoreConsulting Fees (clinical consultant): US National Football League (ERM Associates), U.S.Minor/Major League Baseball; Phoenix/Gavin House and BayCove Human Services

• Some of the medications discussed may not be FDA approved in the manner in which they are discussed including diagnosis(es), combinations, age groups, dosing, or in context to other disorders (eg, substance use disorders)

www.mghcme.org

2017 Past Month Substance Use in Adolescents

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%8th grade

Miech et al., Monitoring the Future, 2017

www.mghcme.org

0

5

10

15

Alcohol

abuse/dependence

Drug

abuse/dependence

Any substance use

disorder

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)

www.mghcme.org

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

Drug Alcohol Depend. 2018 Mar 27;186:242-256.

www.mghcme.org

Age at Onset of DSM-IV Drug

Abuse and Dependence

Compton et al. Arch Gen Psychiatry/ Vol 64, May 2007; 45(11): 1294 - 1303

www.mghcme.org

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

www.mghcme.org

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

www.mghcme.org

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)

www.mghcme.org

Juvenile SUD: Risk and Protective Factors

Familial - runs in families

Genetic – 50% accounted for by “genes”

Environmental – Values, patterns, availability

Self medication – Symptoms, affect intolerance

(Wilens et al., 2000; 2002, 2005, 2013; Nunes et al. 2003; Rhee et al. 2003; Yule et al. AJA 2013)

www.mghcme.org

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

www.mghcme.org

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 (%)

Note: Boldface figures indicate significant results. Dashes indicate analyses were not performed because

of a limited number of data points.

Groenman AP et al. J Am Acad Child Adolesc Psychiatry. 2017

Jul;56(7):556-569

Child Psychopathology Increases Risk for Later SUD

www.mghcme.org

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, 2016; Husson Psych Add Behav 2011; Clarke et al 2004; Riggs et al 2007)

www.mghcme.org

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

Bipolar/Conduct in Adolescence Increases the Risk of SUD in Young Adults

Bipolar

Control

Wilens, et al. J Clin Psychiatry. 2016 .

Non-Persistent Bipolar

www.mghcme.org

MGH Outpatient Young Person SUD Service: Rates of Overdose at Intake (N=155)

Yule et al. J Clin Psych, 2018

OD Linked to Psychopathology

Psychiatric CharacteristicsLikelihood of Overdose vs No Overdose

Odds Ratio

*

*

*

*

*p<0.05

Yule et al. J Clin Psych, 2018

www.mghcme.org

Juvenile SUD: Diagnostics

– Evaluate medical condition including complications (LFT, STDs)

– Generate differential diagnosis for psychiatric/medical symptoms

– Utilize urine, saliva, or hair toxicology screens

(Jackson, Yule, Wilens; Adolescent SUD in Handbook of

Adolescent Medicine, 2nd Edition, 2017)

www.mghcme.org

Medical Cannabis in Children and Adolescents:A Systematic Review

(Wong, S and Wilens, T. Pediatrics. 2017 Oct 23. pii: e20171818. doi: 10.1542/peds.2017-1818)

• Evidence for benefit was strongest for chemotherapy-

induced nausea and vomiting, and for treatment-refractory

epilepsy.

• At this time, there is insufficient evidence to support use for

spasticity, neuropathic pain, posttraumatic stress disorder,

Tourette syndrome, or any psychiatric disorder in childhood.

www.mghcme.org

Putative Medical Uses of THC vs CBD

CBD

Seizures

Pain

Migraines

Anxiety

Depression

Inflammatory diseases (IBD)

THC

Pain

Nausea/Vomiting

Spasticity

Glaucoma

Insomnia

Appetite

www.mghcme.org

“Synthetic” Drugs: Synthetic Marijuana

• Synthetic Marijuana (Spice, K2, Herbal incense)• Cannabis-like high• Chemicals sprayed on herbs• As of 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)

www.mghcme.org

Adolescent SUDPart II: Diagnosis and Treatment

www.mghcme.org

Screening Adolescents for Drugs and Alcohol:S2BI (Levy et al, Pediatrics 2016)

In the past year, how many times have you used:

• Tobacco?

• Alcohol?

• Marijuana?

STOP if all “Never.”

Otherwise, CONTINUE.

• Prescription drugs that were not prescribed for you (such as pain medication or Adderall)?

• Illegal Drugs (such as cocaine or Ecstasy)?

• Inhalants (such as nitrous oxide)?

• Herbs or synthetic drugs (such as salvia, “K2”, or bath salts)?

https://www.drugabuse.gov/ast/s2bi/#/

www.mghcme.org

Documentation

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

www.mghcme.org

Juvenile SUD: Treatment

Stabilization of alcohol / drug misuse

– 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

(Jackson, Yule, Wilens; Adolescent SUD in Handbook of Adolescent Medicine, 2nd Edition, Springer, 2017)

www.mghcme.org

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

• Coping skills

• Reduce SUD “cues”

• Relapse prevention (eg reducing cues, balance in life)

(Wilens, McKowen & Kane Contemp Peds 2013)

www.mghcme.org

Psychopharmacologic Strategies with Juvenile Substance Use Disorders

• 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.Jackson, Yule, Wilens;

Adolescent SUD in Handbook of Adolescent Medicine, 2nd Edition, Springer, 2017)

www.mghcme.org

Pharmacotherapies to Reduce Urge or Cravings

• Nicotine (less effect than adults)– Nicotine patch (most effective in teens), 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

– E-cigs not recommended (e.g. 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).

www.mghcme.org

Pharmacotherapies to Reduce Urge or Cravings

• Alcohol– Naltrexone (Rivea) -reduces alcoholic drinking: dosing 25-50 mg

QD to BID– 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; Yule,

Wilens. Curr Psychiatry. 2014E)

www.mghcme.org

Pharmacotherapy for Marijuana Use Disorders

• N-Acetyl Cysteine (NAC)-natraceutical-dosing 1200 mg BID (RCT; Grey et al. Am J Psych 2012; Drug Alc Depend 2018)

– In adult trials, only early-onset cannabis use disorder responded

• Buspirone (pilot RCT; McRae-Clark et al., 2009)

• 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)

www.mghcme.org

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)

www.mghcme.org

Young people SUD- Comorbidity

• ADHD – Consider addressing both conditions

– Low level substance use–> continue to treat ADHD

– More severe SUD –> address SUD first, if possible

– Can treat ADHD through SUD (nonstim, XR stims only)

• Depression – Co-treat Depression and SUD

– May need to improve SUD to see residual mood symptoms

• Anxiety– Address SUD initially, then anxiety

– Can treat anxiety through SUD (use SSRI/SNRI, buspirone)

• Severe Mood Dysregulation– Treat mood dysregulation and SUD simultaneously

– Use safer agents (e.g. SGAs for mood)

For review, see (Gignac et al. 2010; Yule and Wilens, Curr Psych. 2015; 14(4): 36-39, 47-51.Jackson, Yule,

Wilens; Adolescent SUD in Handbook of Adolescent Medicine, 2nd Edition, Springer, 2017)

www.mghcme.org

ADHD and SUD: Pharmacotherapy

• Treat through cannabis use/misuse• Use disorder -> sequence treatment to address substance

use, then restart ADHD treatment• In refractory SUD cases --> Treat ADHD• Nonstimulants

– Atomoxetine– Guanfacine XR/Clonidine XR– Bupropion

• Stimulants (use extended release; avoid immediate release)– Methylphenidate (e.g. Concerta and equivalent)– Amphetamine (e.g. Vyvanse, Add XR and equivalent)

Wilens T, Morrison N. Current Opinion in Psychiatry. 2011;24:280-285.Wilens and Carrelas, ADHD & SUD, in ADHD Textbook: Children and Adults, Cambridge Press 2016

Levin, et al. JAMA Psychiatry. 2015;72(6):593-602.

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 studyN = 147 subjectsAbstinent from 4-30 days Findings: (ATX vs. placebo)

Improved ADHD ScoresNo differences in relapse rateImproved OCD scoresImproved heavy drinking (shown)

F-U study: Few side effectswith alcohol

(Wilens et al. Drug Alc Dep 2009:96:145-154 2008; Adler et al. Am J Addict 2009:18: 393-401 )

Atomoxetine

Placebo

www.mghcme.org

A RCT of Fluoxetine and Cognitive Behavioral Therapy

in Adolescents with Major Depression and SUD

40

45

50

55

60

65

70

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

10

15

20

25

30

0 4 8 12 16

Week of TreatmentT

ob

acco

Su

bst

an

ce U

se i

n P

ast

30

Da

ys,

Ad

just

ed

Mea

n (

SE

), d

Fluoxetine +

CBT

Placebo + CBT

Substance Use

www.mghcme.org

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

www.mghcme.org

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 mgTopiramate dosing: 75 mg - 150 mg BIDBPD 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)

www.mghcme.org

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)

www.mghcme.org

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; Jackson, Yule,

Wilens; Adolescent SUD in Handbook of Adolescent Medicine, 2nd Edition, Springer, 2017)

www.mghcme.org

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