Addiction: Is It A Chronic Disease?

Thursday, March 24, 2016

Sarah M. Bagley, MD

Clinical Addiction Research and Education Unit

BU School Of Medicine / Boston Medical Center

Medical Director, Adolescent and Young Adult Substance Use Program

Boston Medical Center

Outline

The session will include:

1. Neurobiology of addiction

2. Addiction treatment

Special thanks to Dr. Alex Walley for sharing his slides with

me

Outline

The session will address:

1. Addiction drives crime

2. Addiction is a treatable brain disease

– Typically requires time and multiple attempts

3. Opioid addiction and treatment

4. Stimulant addiction and treatment

5. Criminal Justice – Treatment opportunities

Addiction drives crime

• 48% of federal prisoners there for drug offenses

• 17% of State and 18% of Federal prisoners

committed their crime to obtain money for drugs

• 53% of State and 45% of Federal prisoners meet

DSM-IV criteria for drug dependence or abuse

Mumola, CJ. US Dept. of Justice, 2006; Bureau of Justice Statistics, 2011

Burden of Disease in Corrections

• 53% of State and 45% of Federal prisoners meet

DSM-IV criteria for drug dependence or abuse

• 1/3 of Americans with HCV pass through

corrections each year

• 1/4 of Americans with HIV pass through

corrections each year

• 40% of active TB cases in U.S. prisoners

CDC Publication No. 21-1306 Hammett TM et al. Am J Public Health. 2002;92(11):1789–94.

Baillargeon J et al. Ann Epidemiol. 2000;10:74–80.

McLellan et al. Drug Dependence: A

Chronic Medical Illness. JAMA 2000

• Main point?

– Drug addiction is a diagnosable, treatable

chronic disease

• Genetic heritability, personal choice, and

environmental factors involved in the etiology and

course as they are for DM2 and asthma

• Addiction results in brain changes

• Pharmacotherapy can work for nicotine, alcohol

and opioid, but not stimulant or marijuana addiction

McLellan et al. Drug Dependence: A Chronic Medical Illness. JAMA 2000

NIDA Principles of Drug Abuse Treatment

for Criminal Justice Populations

1. Drug addiction is a brain

disease that affects behavior

2. Recovery from drug addiction

requires effective treatment

3. Treatment must last long

enough to produce stable

behavioral change

4. Assessment is the first step in

treatment

5. Tailoring services is an

important part of effective drug

abuse treatment for CJ

populations

www.drugabuse.gov/sites/default/filespodat_cj_2012.pd

f

NIDA Principles of Drug Abuse Treatment

for Criminal Justice Populations

6. Drug use during treatment

should be monitored

7. Treatment should target

factors associated with

criminal behavior

8. Criminal justice supervision

should incorporate treatment

planning for drug abusing

offenders, and treatments

should be aware of

correctional supervision

9. Continuity of care is essential

re-entering the community

10. A balance of rewards and

sanctions encourages pro-

social behavior

11. Offenders with co-occurring

problems often require an

integrated treatment approach

12. Medications are an important

part of treatment for many

13. Treatment planning should

include strategies to address

medical conditions

www.drugabuse.gov/sites/default/filespodat_cj_2012.pd

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AMPHETAMINE

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MORPHINE

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Source: Di Chiara and Imperato

Drugs Elevate Dopamine Levels More/Longer

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Partial Recovery of Brain Dopamine Transporters

in Abuser After Protracted Abstinence

Normal Control METH Abuser (1 month detox)

METH Abuser (14 months detox)

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ml/gm

Source: Volkow, ND et al., Journal of Neuroscience 21, 9414-9418, 2001.

Addiction is Treatable

Substance Use Careers Last for

Decades

Pe

rce

nt in

Re

co

ve

ry

30 25 20 15 10 5 0

100%

90%

80%

70%

60%

50%

40%

30%

20%

10%

0%

Median

duration of

27 years

(IQR: 18 to

30+)

Source: Dennis ,

Scott, Funk & Foss

( 2005) (n=1,271) Years from first use to 1+ years abstinence

Most people do achieve

abstinence

Years from first Tx to 1+ years abstinence

25 20 15 10 5 0

Median duration

of 9 years

(IQR: 3 to 23)

and 3 to 4

episodes of care

Pe

rce

nt in

Re

co

ve

ry

100%

90%

80%

70%

60%

50%

40%

30%

20%

10%

0% Source: Dennis et

al 2005 (n=1,271)

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

Using

(N=661)

1 to 12 ms

(N=232)

1 to 3 yrs

(N=127)

3 to 5 yrs

(N=65)

5 to 8 yrs

(N=77)

% Days of Psych Prob (of 30 days)

% Above

Poverty Line

% Days Worked For Pay (of 22)

% Clean and

Sober Friends

% Days of Illegal Activity (of 30 days)

Recovery over Abstinence of 8 Years 1-12 Months:

Immediate

increase in clean

and sober friend

1-3 Years:

Decrease in

Illegal Activity;

Increase in

Psych Problems

3-5 Years:

Improved

Vocational and

Financial Status

5-8 Years:

Improved

Psychological

Status

Source: Dennis, Foss & Scott (2007)

Why do people use drugs?

1. To feel good

2. To feel better

Natural History of Opioid Dependence W

ith

dra

wal

Norm

al

Eup

ho

ria

Chronic use Acute use

Tolerance and Physical

Dependence

Maintenance Treatment for Opioid

Dependence W

ith

dra

wal

Norm

al

Eup

ho

ria

Chronic use Maintenance

Opioid Detoxification Outcomes

• Low rate of retention in treatment

• High rates of relapse post-treatment

< 50% abstinent at 6 months

< 15% abstinent at 12 months

Increased rates of overdose due to decreased tolerance

Opioid Maintenance Medication Goals

1. Alleviate physical withdrawal

– 30-40mg

2. “Narcotic blockade”

– 60+ mg

3. Alleviate drug craving

– 60+ mg

4. Normalize brain changes

– takes 6+ months of abstinence

Medication Assisted Treatment First Clinical Trial

JAMA 1965

JAMA 2005

In a Comprehensive

Rehabilitation Program…

Increases overall survival

Increases treatment retention

Decreases illicit opioid use

Decreases hepatitis and HIV

seroconversion

Decreases criminal activity

Increases employment

Improves birth outcomes

Methadone Maintenance Treatment

Highly Structured

• Daily nursing assessment

• Weekly individual and/or group counseling

• Random supervised toxicology screens

• Psychiatric services

• Medical services

• Methadone dosing

– Observed daily “Take homes”

Relapse After Leaving Treatment

Methadone Maintenance Limitations

Highly regulated - Narcotic Addict Treatment Act 1974

Created methadone clinics (Opioid Treatment Programs)

Separate system not involving primary care or pharmacists

Limited access 5 states: 0 clinics, 4 states: < 3 clinics

Inconvenient and highly punitive

Mixes stable and unstable patients

Lack of privacy

No ability to “graduate”

Stigma

Who should get buprenorphine/naloxone

(Suboxone)?

• No evidence that certain patients respond better

to buprenorphine/methadone

• The choice between methadone or

buprenorphine depends upon: – Overall response to each treatment

• Many patients express a clear preference

– Access to treatment setting (e.g., doctors office vs Opioid

Treatment Program)

– Ease of withdrawal

– Patient (and clinician) expectancy

• Pure opioid antagonist

• Oral naltrexone

– Well tolerated, safe

– Duration of action 24-48 hours

– FDA approved 1984

• Injectable naltrexone (Vivitrol®)

– IM injection (w/ customized needle) once/month

– FDA approved 2010

– Patients must be opioid free for a minimum of 7-10 days before treatment

Naltrexone

• 10 RCTs ~700 participants to naltrexone alone or with psychosocial therapy compared with psychosocial therapy alone or placebo

– No clear benefit in treatment retention or relapse at follow up

• Benefit in highly motivated patients

– Impaired physicians > 80% abstinence at 18 months

Cochrane Database of Systematic Reviews 2006

Oral Naltrexone

• Multicenter (13 sites in Russia-OAT unavailable) DB RPCT 24 weeks

• 250 individuals with opioid dependence randomized to XR-NRT vs placebo

• All offered biweekly individual drug counseling

• Funded by pharmaceutical company – Alkermes

Krupitsky E, et al. Lancet, 2011

Injectable Naltrexone (Vivitrol)

Outcomes NTX placebo

Trial completion 53% 38%

Confirmed abstinence at 24 weeks 90% 35%

Change in craving score -10.1 0.7

Other medications for alcohol use

disorders

• Alcohol dependence

– Naltrexone – daily oral or monthly injection

• No abuse potential, opioid blocker

– Acamprosate – 3x daily oral

• No abuse potential, few side effects

– Disulfiram – daily oral

• No abuse potential, makes alcohol toxic

Why do people use stimulants?

• Euphoria - Rush

– Onset and intensity depends on delivery method

• Increased energy, alertness, libido

• Diminished social inhibition

• Decreased appetite

Cocaine and methamphetamine

Binges

• 2-3 day binges are typical, called runs

• Regular re-dosing to maintain rush or high

in setting of acute tolerance

• Ends when drug or money runs out, or

paranoia/ disorganized thinking sets in

Pharmacologic Treatment

• Antipsychotics

– Amato. Cochr Database Syst Rev. 2007 Jul 18;(3):

• Anticonvulsants - GABA modulators

– Carbamazepine, Phenytoin, Valproic Acid, Tigabine, Gabapentin,

Lamotrigine – Alvarez. JSAT 2010: 38; 66-73.

– Baclofen – Heinzerling. Drug Alcohol Depend. 2006 Dec 1;85(3):177-84.

– Vigabatrin (GVG) – Brodie. Am J Psychiatry. 2009;166:1269-77.

• Stimulant replacement

– Modafinil – Shearer. Addiction. 2009 Feb;104(2):224-33.

– Dexamphetamine – Longo. Addiction 2009, 105, 146–154

• Vaccine – Martell. Arch Gen Psychiatry. 2009 Oct;66(10):1116-23.

• Disulfiram – Pani. Cochr Database Syst Rev. 2010 Jan 20;(1):

Non-medical treatment for addiction

• Physician advice and brief intervention

– Evidence is limited to non-dependent, risky alcohol use

• Motivational enhancement therapy

• Cognitive behavior therapy

• Community Reinforcement Approach/ Community Reinforcement and Family Therapy (CRAFT)

• 12-step facilitation

• Contingency management

All treatments require adherence

Coming home

• 95% of prisoners will eventually

be released

• 730,000 released in 2009

– 21 % increase from 2000

• ~13 times increased risk of death in the two weeks

after release

Cuellar AE. Health Aff. 2012 May;31(5):931-8.

Binswanger et al. N Engl J Med 2007;356:157-65

Motor vehicle traffic, poisoning, and drug poisoning (overdose) death rates: United States, 1980-2010

NCHS Data Brief, December, 2011, Updated with 2009 and 2010 mortality data 0

5

10

15

20

25

1980 1982 1984 1986 1988 1990 1992 1994 1996 1998 2000 2002 2004 2006 2008 2010

Dea

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per

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00

po

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on

Year

Motor Vehicle Traffic Poisoning Drug Poisoning (Overdose)

Drug Overdose Death Rates in USA More Than Tripled Since 1990 (Nearly 17,000 in 2010).

More OD Deaths than

MVA Deaths Since 2009

Methadone treatment before and after release from prison

increases treatment retention and reduces drug use

At 12 months post-release, offenders who had received MMT in prison and continued it in the

community were more likely to enter and stay in treatment and less likely to test positive for opioid and

cocaine use than participants who received counseling and referral to methadone, or those who

received counseling with transfer to methadone maintenance upon release.

Outline

The session will address:

1. Addiction drives crime

2. Addiction is a treatable brain disease

– Typically requires time and multiple attempts

3. Opioid addiction and treatment

4. Stimulant addiction and treatment

5. Criminal Justice – Treatment opportunities

Thanks!

Sarah Bagley, MD

sbagley@bu.edu

“Addiction” Diagnosis ~ 23,000,000

Little or No Use

Rare Use

Frequent Use In Specialty Treatment ~ 2,300,000

Source: A. T. McLellan, 2011

(Diabetes ~24,000,000)

“Harmful Use”

~60,000,000

Scope of Substance Use in the U.S.

“Street pills”

• Opioids

– Oxycodone (Percocet,

Oxycontin, Perc 30s)

– Morphine (MS Contin)

– Hydrocodone (Vicodin)

– Hydromorphone (Dilaudid)

– Fentanyl (Duragesic)

– Methadone (Dolophine)

– Buprenorphine/naloxone

(Suboxone)

• Benzodiazepines

– Clonazepam (Klonopin)

– Alprazolam (Xanax)

– Diazepam (Valium)

• Clonidine (Catapress)

• Promethazine (Phenergan)

• Queitiapine (Seroquel)

• Gabapentin (Neurontin)

• Carisoprodol (Soma)

• Z drugs – Ambien and Lunesta

Treating addiction in the criminal justice system is

cost-effective

Methadone treatment cost averages $4,700 compared to $24,000 for state and

federal prison per year

Zarkin et al. 2008. Warren et al. 2008

How long should

methadone maintenance

treatment last?

Long enough.

What should we do with our

stimulant-using patients?

• For both inpatients and outpatients

– Ask about medical complications, overdose

– Harm reduction – safer use techniques

– Motivational interviewing to develop a decisional balance that favors safer use, quitting and engaging in available treatment

• Consider contingency management strategies

Opioid withdrawal

Kosten et al. NEJM 2003; 348: 1786.

Cocaethylene

• Psychoactive substrate from EtOH+cocaine

• ETOH commonly used as “landing gear”

• ETOH before cocaine inhibits cocaine

metabolism, producing cocaethylene

• 60-90% of cocaine abusers abuse ETOH

• Greater cardiac toxicity

• Greater rates of seizures, hepatic damage

Opioid-naïve brain cell

Heroin

Brain cell on opioids Opioid-dependent brain cell without

opioids (aka dopesick)

Brain cell on too many opioids

x x

Heroin

Brain cell on opioids

Heroin Methadone

Relapse

Heroin

Methadone maintenance

Heroin NALOXONE

Overdose reversal Brain cell on too many opioids

x x

Heroin

Opioid withdrawal

METHADONE Methadone

Brain cell during methadone detox

Methadone

Brain cell detoxed

Dose Response

Effects of Psychosocial Services

McLellan, AT et.al , JAMA 1993

Chronic Opioid Withdrawal

• Lasts months to years

• Secondary to derangement of endogenous

opioid receptor system

• Symptoms

– generalized malaise, fatigue

– poor tolerance to stress and pain

– craving for opioids

– restlessness, insomnia

Acute Toxicity

• Elevated BP and HR

• Arrythmia

• Vasoconstriction

• Hyperthermia

• Agitation

• Rhabdomyolysis

• Seizure

• Acute psychosis prolonged psychosis

–Paranoid delusions

–Visual, sensory, and auditory hallucinations

(ie formications)

Long-term Goals of Detox

• Referral to substance abuse treatment

Detoxification program leading to long term

medication-free treatment (e.g. residential

treatment, intensive outpatient treatment)

Medication assisted treatment (e.g.

methadone, buprenorphine)

Is there stimulant withdrawal?

• Intense craving

• Depression

• Fatigue

• Unpleasant dreams

• Hypersomnia, then insomnia

• Increased appetite

• Limited ability to experience pleasure

>> All results of relative dopamine depletion