Transcript Integrated Dual Disorder Treatment

Medication-Assisted
Treatment (MAT) of
Opioid Dependence
Christina M. Delos Reyes, MD
Chief Clinical Officer, ADAMHS Board of Cuyahoga County
Medical Consultant, Center for Evidence-Based Practices at Case
OJACC 25th Annual Conference
Columbus, Ohio
October 13-14, 2011
1
Learning Objectives

Following this presentation, participants will
be able to:
• List three different types of MAT (medicationassisted treatment) for opioid dependence
• Describe the mechanism of action and the proper
dosing for three different types of MAT for opioid
dependence.
• Review common barriers to using MAT in a
variety of treatment settings.
• Develop a plan to overcome barriers to using MAT
2
in a particular treatment setting.
Ritual of a Heroin
User
“A Fort Myers woman in her 30s prepares a heroin
fix at the home of a friend on a recent day. The
woman uses a hypodermic needle to inject heroin,
which she had heated in a spoonful of water, into a
vein in her hand. However, the increased purity of the
drug and a fear of contracting HIV from
contaminated needles, along with the social stigma
associated with needle use, has caused an upsurge in
users snorting and smoking heroin. "You first get an
adrenaline rush, then a sensation of mellow. You lose
sense of time and forget everything,'' the woman said.
"Heroin is easy to find...You can get a bag for $10.”
3
SOURCE: Naples Daily News, 2001.
Opiate/Opioid : What’s the
Difference?


Opiate
A term that refers to drugs or medications that are
derived from the opium poppy, such as heroin,
morphine, and codeine.
Opioid
A more general term that includes opiates as well
as the synthetic drugs or medications, such as
buprenorphine, methadone, meperidine
(Demerol®), fentanyl—that produce analgesia and
other effects similar to morphine.
4
Basic Opioid Facts
Description: Opium-derived, or synthetics which
relieve pain, produce morphine-like addiction,
and relieve withdrawal from opioids
Medical Uses: Pain relief, cough suppression,
diarrhea
Methods of Use: Intravenously injected, smoked,
snorted, or orally administered
5
What’s What?
Agonists, Partial Agonists,
and Antagonists
Agonist
Morphine-like effect (e.g., heroin)
Partial Agonist
Maximum effect is less than a full
agonist (e.g., buprenorphine)
Antagonist
No effect in absence of an opiate or
opiate dependence (e.g., naloxone)
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Opioid Agonists

Natural derivatives of opium poppy
- Opium
- Morphine
- Codeine
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Opium
8
SOURCE: www.streetdrugs.org
Morphine
9
SOURCE: www.streetdrugs.org
Opioid Agonists

Semisynthetics: Derived from chemicals in
opium
- Diacetylmorphine – Heroin
- Hydromorphone – Dilaudid®
- Oxycodone – Percodan®, Percocet®
- Hydrocodone – Vicodin®
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Heroin
11
SOURCE: www.streetdrugs.org
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Opioid
Agonists
13
SOURCE: www.pdrhealth.com
Opioid Agonists

Synthetics
- Propoxyphene – Darvon®, Darvocet®
- Meperidine – Demerol®
- Fentanyl citrate – Fentanyl®
- Methadone – Dolophine®
- Levo-alpha-acetylmethadol – ORLAAM®
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Methado
ne
Darvocet
15
SOURCE: www.methadoneaddiction.net
Opioid Partial Agonists


Buprenorphine – Buprenex®, Suboxone®,
Subutex®
Pentazocine – Talwin®
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Buprenorphine/Naloxone combination
and Buprenorphine Alone
17
Opioid Antagonists

Naloxone – Narcan®

Naltrexone – ReVia®, Trexan®
18
Opioids and the Brain:
Pharmacology
and Half-Life
19
20
SOURCE: National Institute on Drug Abuse, www.nida.nih.gov.
Terminology
Receptor:
specific cell binding site or molecule: a molecule,
group, or site that is in a cell or on a cell surface
and binds with a specific molecule, antigen,
hormone, or antibody
21
Opioid Agonists:
Pharmacology


Stimulate opioid receptors in central
nervous system & gastrointestinal tract
Analgesia – pain relief (somatic &
psychological)

Antitussive action – cough suppression

Euphoria, stuperousness, “nodding”

Respiratory depression
22
Opioid Agonists:
Pharmacology






Pupillary constriction (miosis)
Constipation
Histamine release (itching, bronchial
constriction)
Reduced gonadotropin secretion
Tolerance, cross-tolerance
Withdrawal: acute & protracted
23
What is the Definition of
“Half-Life?”
The time it takes for half a given amount of a
substance such as a drug to be removed from living
tissue through natural biological activity
24
Duration of Action
•
•
Two factors determine the duration of action of
the medication:
Half-life - time it takes to metabolize half the
drug. In general, the longer the half-life, the
longer the duration of action.
Receptor affinity or strength of the bond
between the substance and the receptor medications that bind strongly to the receptor
may have very long action even though the
half-life may be quite short.
25
Opioid Antagonist HalfLives

Naloxone – 15-30 minutes

Naltrexone – 24-72 hours
26
Opioid Agonist Half-Lives

Heroin, codeine, morphine – 2-4 hours

Methadone – 24 hours

LAAM – 48-72 hours
27
Opioid Partial Agonist
Half-Lives

Buprenorphine – 4-6 hours (however, duration of
action very long due to high receptor affinity)

Pentazocine – 2-4 hours
28
Opioid Addiction
and the Brain
Opioids attach to receptors in brain
Repeated opioid use
Pleasure
Tolerance
Absence of opioids after prolonged use
Withdrawal
29
What Happens When
You Use Opioids?

Acute Effects: Sedation, euphoria, pupil
constriction, constipation, itching, and lowered
pulse, respiration and blood pressure

Results of Chronic Use: Tolerance, addiction,
medical complications

Withdrawal Symptoms: Sweating, gooseflesh,
yawning, chills, runny nose, tearing, nausea,
vomiting, diarrhea, and muscle and joint aches
30
Possible Acute Effects
of Opioid Use



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
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
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Surge of pleasurable sensation = “rush”
Warm flushing of skin
Dry mouth
Heavy feeling in extremities
Drowsiness
Clouding of mental function
Slowing of heart rate and breathing
Nausea, vomiting, and severe itching
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Consequences of Opioid Use

Addiction

Overdose

Death

Use related (e.g., HIV infection, malnutrition)

Negative consequences from injection:
•
•
•
•
•
•
Infectious diseases (e.g., HIV/AIDS, Hepatitis B and C)
Collapsed veins
Bacterial infections
Abscesses
Infection of heart lining and valves
32
Arthritis and other rheumatologic problems
Heroin Withdrawal Syndrome

Intensity varies with level & chronicity of use

Cessation of opioids causes a rebound in function
altered by chronic use

First signs occur shortly before next scheduled dose

Duration of withdrawal is dependent upon the halflife of the drug used:
• Peak of withdrawal occurs 36 to 72 hours after last dose
• Acute symptoms subside over 3 to 7 days
• Protracted symptoms may linger for weeks or months
33
Opioid Withdrawal
Syndrome
Acute Symptoms

Pupillary dilation

Lacrimation (watery eyes)

Rhinorrhea (runny nose)

Muscle spasms (“kicking”)

Yawning, sweating, chills, gooseflesh

Stomach cramps, diarrhea, vomiting

Restlessness, anxiety, irritability
34
Opioid Withdrawal
Syndrome
Protracted Symptoms

Deep muscle aches and pains

Insomnia, disturbed sleep

Poor appetite

Reduced libido, impotence, anorgasmia

Depressed mood, anhedonia

Drug craving and obsession
35
Treatment Options for
Opioid-Addicted
Individuals

Behavioral treatments educate patients about the
conditioning process and teach relapse prevention
strategies.

Medications such as methadone and
buprenorphine operate on the opioid receptors to
relieve craving.

Combining the two types of treatment
enables patients to stop using opioids
and return to more stable and
productive lives.
36
Treatment Options for
Opioid-Addicted
Individuals

Medically-assisted withdrawal

Long-term residential treatment

Outpatient psychosocial treatment

Behavioral therapies

Medication-Assisted Treatment (MAT)
37
Medication-Assisted
Treatment
 Naltrexone—antagonist
 Methadone—agonist
 Buprenorphine—partial agonist
38
Naltrexone


Opiate antagonist to treat opiate dependence
All effects of opiates are blocked
• Must be detoxed and opiate-free or else will cause
opiate withdrawal syndrome


Blocks opioid receptors that are involved in
the rewarding effects of opiates (& alcohol!)
Risk for hepatotoxicity
• Monitor for liver enzymes
39
Naltrexone





Brand name: Revia (oral tablets)
Usual dose: 50mg daily
Efficacy highest in patients who can abstain
for 4 to 7 days before initiating treatment
No negative effect with use
Some clients notice anxiolytic effect
40
Long- Acting Naltrexone





Brand name is Vivitrol
Approved for alcoholism in 2006
Approved for opiate dependence Oct 2010
Given monthly, 380 mg appears to have
increased efficacy versus 190 mg
May have increased efficacy for men vs.
women, and those abstinent when medication
is initiated vs. those still drinking
41
Long- Acting Naltrexone


Discontinuation rate- 14% in patients on 380
mg a month, 7% in patients on 190 mg a
month and placebo. Most common side
effects: nausea, injection site reaction,
headache.
LFTs remained stable throughout the
medication trial
42
Naltrexone:
Recent Research



2005: Cuts the relapse risk during first 90 days
by 36% (28% relapse rate on oral naltrexone
vs. 43% relapse rate on placebo)
2005: injectable naltrexone resulted in a 25%
reduction in proportion of heavy drinking days
vs. placebo
Overall: helps to curb consumption in patients
with multiple “slips” but less effective in
maintaining abstinence
43
Naltrexone


Non-compliance is the main barrier to success
Most useful for highly motivated patients w/
external circumstances
• Impaired professionals, parolees, probationers, etc
44
Methadone



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Opiate agonist to treat opiate dependence
Well-studied and effective treatment
• Normalizes function/return to work, decreases
crime/violence, reduces HIV exposure
Doses > 70mg/day generally better than low doses
Enhanced services = improved outcomes
• Counseling, medical, social/vocational services,etc
No contraindication in SMI, though not well studied
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Methadone




Usually taken once a day to suppress
withdrawal for 24 to 36 hours
Usually given in liquid form by Opiate
Treatment Programs
Induction phase—no more than 30 to 40 mg on
the first day of treatment
Dosage changes usually occur once a week
• More rapid dosage increases can cause overdose

Maintenance phase—usually 80-120mg daily46
Methadone

Common side effects
• Sweating, constipation, abnormal libido, sleep
abnormalities, mild anorexia, weight gain, water
retention

Adverse effects
• Prologation of QTc (usually seen with very high
doses, mean of 350mg daily)
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Buprenorphine
 Opioid partial agonist
  risk of overdose and  abuse potential
 May precipitate opiate withdrawal in dependent
individuals
 Approved for treatment of opiate dependence
• Maintenance dose in the range of 8-16 mg daily
 Sublingual route of administration
 Subutex= Bup only; Suboxone= Bup + Naloxone
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Buprenorphine


Approved in U.S. (2002) as office-based
treatment vs. ‘methadone clinics’
Individual doctors may treat up to 30 patients
at a time, using an special DEA #
• After 1 year, may increase to 100 patients

Must be addiction medicine/addiction
psychiatry certified OR complete 8-hr training
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Direct Buprenorphine Induction
from Short-Acting Opioids


Ask patient to abstain from short-acting opioid (e.g.,
heroin) for at least 6 hrs. and be in mild withdrawal
before administering buprenorphine/naloxone.
When transferring from a short-acting opioid, be sure
the patient provides a methadone-negative urine screen
before 1st buprenorphine dose.
SOURCE: Amass, et al., 2004, Johnson, et al. 2003.
Buprenorphine

Suboxone= buprenorphine + naloxone in a 4:1
mixture
• Available doses: 8/2mg and 2/0.5mg
• 2 sublingual forms: tablet and Film


Induction phase Day 1: usual dose is 2 mg
given every 2-3 hours, up to 8 mg
Induction phase Day 2: start with 8mg, can go
up to 16mg depending on patient symptoms
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Buprenorphine




Maintenance phase: usually 8 to 16 mg daily
This may vary in clinical practice, but realize
that 16mg dose covers ~95% of opiate
receptors
Adverse side effects: Increased LFTs, cytolytic
hepatitis
Common side effects: generally mild
• Constipation; dizziness; drowsiness; headache;
nausea; sweating; vomiting;
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Buprenorphine:
Recent Research

The SAMHSA Evaluation of the Impact of the DATA Waiver
Program
• FINAL REPORT in March 2006





Buprenorphine clinically effective and well accepted by
patients.
Waiver Program has  the availability of medication-assisted
treatment for opioid addiction.
Adverse effects, whether involving diversion or adverse
clinical events or public health consequences, have been
minimal.
The 30-patient limit on individual physician practices and cost
/ reimbursement issues may be decreasing potential access to
treatment.
For more information, see www.buprenorphine.samhsa.gov 53
Partial vs. Full Opioid Agonist
death
Opiate
Effect
Full Agonist
(e.g., methadone)
Partial Agonist
(e.g. buprenorphine)
Antagonist
(e.g. Naloxone)
Dose of Opiate
54
Possible Barriers
to using MAT
Potential Fear # 1:
Medication will
eventually replace
rehabilitation as the
treatment of choice for
addiction “a pill for
every ill”



Rationale # 1:
Medication may be a
useful adjunct to
treatment
“Another tool in your
toolbox”
55
Possible Barriers
to using MAT
Potential Fear # 2:
Medication will distract
from the difficult work
of recovery from
addiction




Rationale # 2:
Medication makes detox
safer and more humane
Medication may allow
the process of recovery
to begin and continue
Medication may make
recovery possible for
those with severe
mental illness
56
Possible Barriers
to using MAT
Potential Fear # 3:
Medication will perpetuate
an existing addiction
Potential Fear # 4:
Medication will cause new
addictions




Rationale # 3:
Physical dependence to
medication may occur,
but addictive behavior
should decrease
Rationale # 4:
New addictions to
medications are a risk,
but the actual incidence
is quite low
57
Other Barriers to MAT?

Financial
• MAT may be very expensive and many still do not
have insurance

Regulatory


Until very recently, doctor visits for MAT were not
covered by ODADAS
Logistical
• Usual treatment settings may not be set up to
provide MAT

Others?
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Medications only work if…


…they are getting “from the bottle to the
bloodstream”
How to help clients with the idea of starting
meds?
• “that will mean I am really sick…” OR “I don’t
need a crutch…”

How to help clients with the idea of staying on
meds?
• “I feel fine, I don’t need it anymore” OR “if I take
meds, then I am not really sober”
Some Lessons from
Motivational Interviewing






What are the client’s goals?
How does medication fit (or not fit) with those
goals?
What are the pros and cons of the medications?
Use of reflective listening
What is the patient willing to do right now?
What are the patient’s fears about medication?
Overcoming
Barriers to MAT


Small group discussion
Large group discussion
61
Hope for Recovery


People with addictive disorders often lack
experiences of success and have lost hope
Medications in conjunction with other
interventions can increase hope for a better life
• Reduced symptoms of withdrawal
• Reduced symptoms of craving
• Support for long-term sobriety
62
Resources



“BUPRENORPHINE TREATMENT:
A TRAINING FOR MULTIDISCIPLINARY
ADDICTION PROFESSIONALS”
• http://www.nida.nih.gov/blending/buptreatmen
t.html
NIDA Methadone Research Web Guide
http://international.drugabuse.gov/collaboration/P
DFs/MethadoneResearchWebGuide.pdf
Mid-America Addiction Technology Transfer Center.
Psychotherapeutic Medications 2011: What Every
Counselor Should Know. http://www.mattc.org
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Contact Information
Christina M. Delos Reyes, MD
Chief Clinical Officer
ADAMHS Board of Cuyahoga County
Phone: 216-241-3400 x 728
Fax: 216-241-0805
[email protected]
Center for Evidence-Based Practices at Case
www.centerforebp.case.edu