Transcript Medications in the Treatment of Substance Use Disorders

Medication-Assisted Treatment and
Recovery with Methadone or
Buprenorphine: What Really Are They?
Yngvild Olsen, MD, MPH
Maryland Addictions Directors Council Conference
May 1, 2014
Objectives
1. Understand the science behind medications
used to help treat opioid use disorder
2. Review two currently available medications
3. Identify indications for specific medications
4. Address myths about methadone and
buprenorphine
Case
38 year old female who has been using heroin and
cocaine intravenously for 20 years, has never been in
treatment, has had two prior arrests for possession,
serving sentences for both. She has hepatitis C,
depression, hypertension, and diabetes but no
regular health care. She is seen in the Emergency
Department for headache with a blood pressure of
190/110 and a finger stick of 380.
The ED physician mentions substance use disorder
treatment including a medication, perhaps
methadone or buprenorphine.
Her questions
• Isn’t being on one of those medications
(methadone or buprenorphine) just substituting
one addiction for another?
• How long would I need to take it?
• What would happen to me while I was taking
methadone or buprenorphine?
• Will I go through withdrawal when I want to come
off?
BACKGROUND INFORMATION
Basic Definitions
Addiction
– A primary, chronic disease of brain reward, motivation,
memory and related circuitry. Dysfunction in these
circuits leads to characteristic biological, psychological,
social and spiritual manifestations.*
– A chronic, relapsing disease characterized by
compulsive drug seeking and use despite harmful
consequences as well as neurochemical and molecular
changes in the brain.**
– A brain disease that affects behaviour.
*American Society of Addiction Medicine
**National Institute on Drug Abuse (NIDA)
Basic Definitions
Physical Dependence
– An adaptation of the body to a specific substance
so that in the absence of that substance a
withdrawal syndrome develops. The withdrawal
syndrome may be relieved in total or in part by
readministration of the substance.
Basic Definitions
Tolerance
– A state in which an increased dose of a
substance is needed to produce a desired
effect
Why do some people develop addiction?
Genetic Variants of the Human Mu Opioid Receptor:
Single Nucleotide Polymorphisms in the Coding
Region Including the Functional A118G (N40D) Variant
HYPOTHESIS
Gene variants:
• Alter physiology
“PHYSIOGENETICS”
• Alter response to
medications
“PHARMACOGENETICS”
• Are associated with
specific addictions
Slide Source: Dr. Kreek
Bond, LaForge… Kreek, Yu, PNAS, 95:9608, 1998; Kreek, Yuferov and LaForge, 2000
Lifetime Prevalence and Odds Ratios of Mental Disorders
by Substance Use Disorder: ECA
Alcohol
Drug
Comorbid
Disorder
%
O.R.
%
O.R.
Any mental
36.6
2.3
53.1
4.5
3.8
3.3
6.8
6.2
Affective
13.4
1.9
26.4
4.7
Anxiety
19.4
1.5
28.3
2.5
Antisocial
14.3
21.0
17.8
13.8
Schizophrenia
(Regier et al., JAMA 264:2511-2518, 1990)
Route of Administration
• The faster a drug gets to the brain, the more
addictive it is
– Injecting
– Smoking
– Snorting
– Oral
– Across the skin
Duration of Action
• The shorter acting a drug is, the more
addictive potential it has
– Heroin
– Cocaine
– Xanax
Potency
• More potent drugs have higher addictive
potential
• Takes less of drug to achieve effect
• Potent drugs:
– Heroin
– Crack
– Fentanyl
• Less potent:
– Marijuana
– Codeine
How does opioid addiction
develop?
The Human Brain
The limbic system contains the reward or pleasure center of the brain
The Human Brain
Source: NIDA. www.drugabuse.gov
The Reward Pathway
1. Neurotransmitter binds to receptor on second cell
2. This binding excites the second cell into action
3. The reward center in the limbic system contains thousands of
nerves and many different neurotransmitters
Dopamine
Dopamine
Innate Opioid Receptor System
• Purpose
– Regulate pleasure
– Regulate pain
The Reward Center and Endorphins
dopamine
receptor
opioid
receptor
dopamine
endorphin
Reward center activation
But……
• All substances of abuse target the reward
center and hijack it
Cocaine
Heroin
The Reward Center and Opioids
dopamine
receptor
opioid receptor
dopamine
Heroin
Euphoria!
Why is euphoria from drugs a bad thing?
•
Overwhelms natural process for feeling
pleasure
•
The brain remembers the intense
pleasure brought about by drugs. These
memories drive continued use and
implicated in relapse
Over time……..
Receptor Changes
• Changes happen in the shape of opioid
receptors with chronic, prolonged exposure
 These changes alter the way nerve cells in the
brain act
• These changes may be irreversible (or at least
long-term)
• May be why so many people relapse after
detox or after years of not using
Opioid Withdrawal Syndrome
• With chronic exposure to opioids, the receptors
and the cells get used to being activated by the
opioid
• This means it takes more opioids to get the same
feeling (tolerance)
• When suddenly the receptor is empty, the cells
can’t act and withdrawal occurs (physical
dependence)
Addiction Vs. Physical Dependence
Source: NIDA.
www.drugabuse.gov
Symptoms of Opioid Withdrawal
–
–
–
–
–
–
–
–
–
–
–
–
–
–
Dysphoria: anxiety, irritability, restlessness
Hot and cold flashes
Goose bumps
Yawning
Runny nose
Watery eyes
Diarrhea
Abdominal cramps
Joint and body pains and aches
Headache
Dilated pupils
Nausea, vomiting
Insomnia
Fever
Summary
• All born with endorphin opioid system that helps
us feel pleasure and regulate pain
• Too much opioids taken into body overstimulate
the reward center
• With repeated exposure to opioids, the body
adapts so that long-term changes happen to the
receptors and cells in the brain
• These changes are manifested by tolerance,
withdrawal, and memory of overstimulation, all of
which drive continued drug use
Why are methadone or buprenorphine then
different from opioids of abuse?
Pharmacologic Mechanism of Heroin
• Binds to opioid receptors in the reward
center of the brain
• Produces intense euphoria
• Route of administration:
– Snort
– Injection
• Short-acting
• Causes physical dependence
Heroin Dose-Response
Pharmacologic Mechanism of Heroin
High
Normal
Withdrawal
Time
Pharmacologic Mechanism of Methadone and
Buprenorphine
• Binds to opioid receptors in the reward center of
the brain
• Route of administration: oral (methadone),
sublingual (buprenorphine)
• Long-acting
• Causes physical dependence
• In people with opioid addiction, at the correct
dose, does not overstimulate the reward center
Methadone/Suboxone Dose-Response
Mu Receptor Activation
Full agonist
methadone
mu receptor site
Partial agonist
buprenorphine
mu receptor site
Antagonist
mu receptor site
naloxone
Partial Agonist Activity Levels
100
Full Agonist (e.g. heroin)
90
80
70
60
But due to its “ceiling”
maximum opioid agonist effect
is never achieved
%
Mu Receptor 50
Intrinsic
40
Activity
Partial Agonist (e.g. buprenorphine)
30
20
Like full agonists, partial agonist drugs
produce increasing mu opioid receptor
specific activity at lower doses
10
0
no drug
low dose
DRUG DOSE
high dose
Treatment Effectiveness
 Goal of treatment is to return to productive
functioning
 Reduces drug use by 40-60%
 Drug treatment is as successful as treatment of
diabetes, asthma, and hypertension
 Strongest predictor of recovery is retention in
treatment
Benefits Of Treatment Including
Methadone
• Reduces risk of HIV infection
• Reduces risk of infection with hepatitis C
and B
• Increases rates of employment among
patients as a group
• Decreases crime
• Increases length of life
Maintenance Treatment Using Buprenorphine
• Numerous outpatient clinical trials comparing
efficacy of daily buprenorphine to placebo, and
to methadone
• Consistently find:
–Buprenorphine more effective than placebo
–Buprenorphine equally effective as moderate
doses of methadone
Example: Buprenorphine and HAART
Adherence
• Roux et al demonstrated improved adherence to
HAART among IV heroin users treated with
buprenorphine in outpatient medical clinic*
• Sullivan et al found significant reduction in HIV
RNA levels among 13 IV heroin users treated with
buprenorphine in HIV clinic**
*Roux et al, Addiction, 2008
** Sullivan et al, CID, 2006
Effect of Medications on Opioid Use
100
Opioid Positive Urine Specimens
Percent Positive
80
60
LAAM
40
Buprenorphine
High Dose Methadone
20
Low Dose Methadone
0
1
2
3
4
5
6
7
8
9 10
11
12
13 14
15 16
17
From: Johnson et al., 2000
Treatment Outcomes For Tapering off
Medication
In methadone studies, 50-80% relapse within one year
after taper
91% of patients receiving buprenorphine for 4 months
had relapsed to prescription opioids within 2 months of
taper*
Opioid overdose fatality rates are 3 to 20 times higher in
the month after tapering off than during treatment
*Weiss R. et al. NIDA CTN Prescription Opioid Treatment Study.
http://www.medscape.com/viewarticle/722342
But......
• Methadone and Suboxone can be abused
• People can overdose on methadone (not as
easy on Suboxone)
• Neither methadone nor Suboxone affect other
drugs of abuse
–
–
–
–
Benzodiazepines
Alcohol
Cocaine
Other pills (phenergan, clonidine)
Side Effects of Methadone and
Buprenorphine
•
•
•
•
•
•
•
•
•
Respiratory depression
Sedation
Constipation
Decreased libido and sexual dysfunction
Headache (primarily buprenorphine)
Sweating (primarily methadone)
Loss of appetite and dry mouth
Nausea, vomiting
Heart arrhythmias (high doses of methadone)
• Medication interactions
Indications for Medications
• All patients with opioid use disorder should be
offered medication as a component of treatment
• The choice of medication is a medical decision
between a physician and a patient
– Weighing complete history, physical examination, and
relevant laboratory testing
• Factors to consider
– Methadone heavily structured and regulated
– Buprenorphine is expensive but less structured
– Naltrexone contra-indicated if prescription opioids are
part of chronic pain treatment
Components of Comprehensive
Drug Addiction Treatment
www.drugabuse.gov
Case
38 year old female
• Using heroin and cocaine intravenously for 20 years
• No h/o treatment
• Two prior arrests for possession, sentences for both.
• Hepatitis C, depression, hypertension, and diabetes
but no regular health care.
• In ED for headache with a blood pressure of 190/110
and a finger stick of 380.
Methadone or buprenorphine?
Her questions
• Isn’t being on methadone or
buprenorphine just substituting one
addiction for another?
• What will happen to me?
• How long do I need to be on it?
• Will I go through withdrawal when I want
to come off?
Substituting one addiction for
another?
• Methadone and buprenorphine treat
withdrawal and physical dependence
• Medications and counseling treat opioid
addiction
• On the right dose of medication, people
function normally, are not getting high, and
are not addicted
How long do I need to take it?
• Individualized
• Less than 90 days in any treatment setting is of
limited to no effectiveness
• Staying on medication in combination with
counseling results in better outcomes than detox
– May include decreasing dose to minimal
effective dose
• Goal is recovery
Protective Factors for Sustained
Recovery after Medication Taper
1. Stable housing
2. Outstanding legal issues resolved
3. Employment or education or other activities
that provide daily purpose and focus
4. Other medical conditions are stable and being
managed
5. Other mental health conditions are stable and
being managed
6. Other substance use disorders are stable and
being managed
7. Solid recovery support network
Will I go through withdrawal when I
want to come off?
• Slow tapering of dose causes minimal
withdrawal and reduces relapse risk
• Should be done under medical supervision
and monitoring
• There is no rush!
MANY PATHS TO RECOVERY!