Download Medication Assisted Treatment for Substance Use Disorders in

Medication Assisted Treatment for
Substance Use Disorders in
Primary Care
Elinore F. McCance-Katz, MD, PhD
Professor of Psychiatry
University of California San Francisco
In This Presentation:
Review some of the basics of pharmacotherapy
treatments that can be accomplished in primary
care and mental health settings
• Tobacco
• Alcohol
• Opioids
Why Do We Need to Know About
Substance Abuse Pharmacotherapy?
Problem Substance Use is Prevalent in Americans
Risky Drinking: Binge (>5 drinks/sitting)
Heavy (> 5 d/mo binge drinking)
23%
6.7%
Illicit Drug Use
8.9%
Substance Abuse or Dependence
8.7%
Alcohol
5.9%
Illicit Drugs
Alcohol and Illicit Drugs
1.7%
1.1%
SAMHSA, National Survey on Drug Use and Health, 2010
What Can Primary Care and
Mental Health Clinicians Use to
Treat Substance Use Disorders?
Selected Pharmacotherapies
General Considerations for SUD
Pharmacotherapy
• Tobacco: Relapse Prevention
• Alcohol
₋ Acute withdrawal (usually done inpatient)
₋ Relapse Prevention-Yes
• Opiates
₋ Acute withdrawal (often done inpatient, but can be outpatient
procedure)
₋ Relapse Prevention-Yes
• Cocaine/Methamphetamines/Stimulants
₋ No FDA approved medications for withdrawal symptoms or
relapse prevention
When to Consider Pharmacotherapy
• Consider Precipitant To Treatment And Severity of
Associated Medical/Psychiatric/Psychosocial Problems:
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Family
Employment
Financial
Medical
Legal
Psychiatric comorbidity (including risk for harm to self or others)
Relapse Potential
• The higher the acuity or severity; greater need for use of
medication treatment (if there is an appropriate medication
intervention available)
• Most FDA approved medications for SUDs can be used in
primary care
• Exception: Methadone maintenance therapy
When to Consider Pharmacotherapy
• Most FDA approved medications for SUDs
can be used in outpatient settings
• Exception: Methadone maintenance
therapy: can only be used for treatment of
opioid addiction in licensed narcotic
treatment programs
Health Effects of Cigarette Smoking
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1200 deaths/day
Lung Cancer
COPD
Cardiovascular diseases
Therefore, screening is recommended and at
least a brief intervention should be offered to
all current smokers
MAT Effective Used with Counseling
• There is a strong dose-response relationship between the
intensity of tobacco dependence counseling and its
effectiveness.
• Effective treatments: person-to-person contact (via individual,
group, or proactive telephone counseling)
• Types of effective counseling: practical counseling (problem
solving/skills training), provision of social support, help in
securing social support outside of treatment
• Brief interventions (as short as 3 minutes) have been shown
to increase quit rates (congratulations on any success,
encouragement for abstinence, health benefits, discussion of
any problems to maintaining abstinence).
Who Should Be Offered
Pharmacotherapy?
All patients willing to attempt to quit smoking
Exceptions:
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Those with medical contraindications
Those smoking fewer than 10 cigarettes/d
Pregnant/breastfeeding women
Adolescents
Smokeless tobacco users
Consider risk/benefit
Cigarette Smoking
FDA approved:
• Nicotine Substitution (Agonist Therapy)
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Nicotine gum
Nicotine lozenge
Nicotine patch
Nicotine nasal spray
Nicotine inhaler
• Bupropion (approved for treatment of
depression and smoking cessation)
• Varenicline (nicotine partial agonist)
Nicotine gum:
Cigarette Smoking
• Reduces nicotine withdrawal: anger/irritability, depression,
anxiety, decreased concentration
• Effect on craving is minimal
• 2 or 4 mg gum; use over 30 min
• Use 4 mg dose for heavy smokers >25 cigarettes daily
• Dosing: 1 piece/hr better than prn for craving
• 50-90% nicotine released depending on chewing rate
• Absorbed through buccal mucosa
• Peak concentrations in 15-30 min (compared to 1-2 min for
cigarette smoking)
• Avoid acidic foods/beverages: e.g.: coffee, juices, soda as these
decrease absorption of nicotine
• Pregnancy Class D: risk to fetus has been shown, but use could
be justified in some cases
Cigarette Smoking
Nicotine gum
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Length of treatment is up to 12 weeks
Cost: $48/2 mg gum
$63/4 mg gum
Boxes with 100-170 pieces
Abstinence rate: approx 50%
(see U.S. Public Health Service: A clinical practice guideline for treating tobacco use and
dependence: A US public health service report. J Am Med Assoc 2000; 283: 3244–3254)
Cigarette Smoking
Nicotine lozenges: 2 and 4 mg (2 mg for those who
smoke more than 30 min after waking up)
• 1 lozenge every 1–2 hours during Weeks 1-6, using a
minimum of 9 lozenges/day
• then decrease lozenge use to 1 lozenge every 2–4 hours
during weeks 7–9
• then decrease to 1 lozenge every 4–8 hours during weeks
10–12.
• NTE: 20/d
• 6 week post treatment quit rate with 4 mg lozenge: 49%
• 2 mg, 72 lozenges per box = $34
4 mg, 72 lozenges per box = $39
Cigarette Smoking
Nicotine Inhaler
• Available by prescription only
• Not a pulmonary effect; nicotine delivered to oropharynx
and absorbed
• A cartridge delivers a total of 4 mg of nicotine over 80
inhalations over 20 min. with absorption of 2 mg
• 6 ng/ml over 20 min vs. 49 ng/ml over 5 min.
• Recommended dosage is 6–16 cartridges/day
• Recommended duration of therapy is 12 weeks, but up to
6 months.
• 1 box of 168 10-mg cartridges = $196
Cigarette Smoking
Transdermal Nicotine Patch
• 16 h patch delivers 14 mg nicotine
• 24 h patch delivers 21 mg nicotine
• Peak levels 6-10 h after application
• Length of Treatment: 8 weeks as effective as longer
periods
• 4 weeks: 21 mg/24 hours
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then 2 weeks: 14 mg/24 hours
then 2 weeks: 7 mg/24 hours
• Side effects: local irritation, mild gastric, sleep
disturbances
• End of treatment smoking cessation: 18-77%
• 6 month abstinence rates: 22-42%
• Can use patch and gum together
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7 mg, box (14 patches) = $37
14 mg, box = $47
21 mg, box = $48
Cigarette Smoking
Nicotine Nasal Spray
• Rapid delivery system of 1 mg nicotine (0.5
mg/nostril/dose)
• Peak nicotine blood level in 10 minutes
• Rapid relief of withdrawal and craving
• Associated with greater sense of control
• 1-2 doses/h; min: 8/d; max 40/d; Use 3-6 mos
• Side effects: throat irritation, coughing, sneezing,
lacrimation; don’t use in active airway disease
• Use in those who fail nicotine gum and/or patch
• Highest potential for dependence 15-20% will use longer
than recommended (6-12 mos)
• $49 per bottle/ 100 doses/bottle
Cigarette Smoking
Bupropion
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Dopaminergic/noradrenergic
Dose: 300 mg daily IR or sustained release
Quit after 7-14 days of treatment
Treatment: 12 weeks; up to 6 mos.
Adverse events: dry mouth, insomnia, stimulation
Do not use in patients with history of seizures or bulimia
Can supplement with gum or patch
Antidepressant effects
60 tablets, 150 mg = $97 per month (generic)
Cigarette Smoking
Varenicline
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Nicotine partial agonist
Decreases craving to smoke
Twice daily oral medication to be started 1 week before
quit date (.5 mg/d x 3d; .5 BID x 4d; 1 mg BID)
Length of Treatment: 12 weeks; max: 6 mos
Monitor for depression/agitation/suicidal thinking
Get psychiatric history prior to prescribing
No abuse liability
1 mg, box of 56 = $131 (28-day supply)
Maintenance Medications To Prevent
Relapse To Alcohol Use
(FDA approved)
• Disulfiram
• Naltrexone (oral and injectable)
• Acamprosate
Clinical Guidance on Use of MAT
Clinical Guidance materials available from SAMHSA:
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TIP 49 Incorporating Alcohol Pharmacotherapies into Medical Practice
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http://store.samhsa.gov/product/TIP-49-Incorporating-AlcoholPharmacotherapies-Into-Medical-Practice/SMA09-4380
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SAMHSA Advisory: Naltrexone for Extended Release Injectable
Suspension for Treatment of Alcohol Dependence
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All SAMHSA materials available at no cost
Pharmacotherapy of Alcohol
Dependence: Naltrexone
• Oral Naltrexone Hydrochloride
₋ DOSE: 50 mg per day
• Extended-Release Injectable Naltrexone
(Garbutt et al, JAMA 2005)
₋ 1 injection per month/ 380 mg
Naltrexone Delays the Onset of
Relapse to Alcohol
Relapse: > 5/>4 men/women drinks at one sitting
Naltrexone
Potent inhibitor at mu opioid receptors:
• May explain reduction in relapse/craving
• Because endogenous opioids involved in the reinforcing
(pleasure) effects of alcohol and possibly craving
Naltrexone Safety
• Can cause hepatocellular injury in very high doses
(eg 5-10 times higher than normal)
• Contraindicated in acute hepatitis or liver failure
• Check liver function before, q1 month for 3 months,
then q 3 months
• Contraindicated if patient needs opioid analgesia
• Caution about ibuprofen and other non-steroidal
anti-inflammatory agents
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may have additive hepatic effects
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Common AEs: nausea/headache
VA/DoD CPG SUDs, www.oqp.med.va.gov/cpg/SUD/SUD_Vase.htm
Disulfiram
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How it Works: Blocks alcohol metabolism leading to increase in blood
acetaldehyde levels; aims to motivate individual not to drink because they
know they will become ill if they do (Goodman and Gilman, 2001)
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Antabuse reaction: flushing, weakness, nausea, tachycardia, hypotension
₋ Treatment of alcohol/disulfiram reaction is supportive (fluids,
oxygen)
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Side Effects:
₋ Common: metallic taste, sulfur-like odor
₋ Rare: hepatotoxicity, neuropathy, psychosis
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Contraindications: cardiac disease, esophageal varices, pregnancy,
impulsivity, psychotic disorders, severe cardiovascular, respiratory, or
renal disease, severe hepatic dysfunction: transaminases > 3x upper level
of normal
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Avoid alcohol and alcohol containing foods
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Clinical Dose: 250 mg daily (range: 125-500 mg/d)
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Adherence: problem; but if drug is taken it works well (Fuller et al. 1994;
Farrell et al. 1995); good idea to start in a substance abuse treatment
program
Alcohol Relapse Prevention Meds:
Acamprosate
• How it works: Acamprosate is an amino acid derivative of taurine that stabilizes
glutamatergic neurotransmission altered during withdrawal (Littleton 1995);
Impact is anticraving, reduced protracted withdrawal.
• Side Effects: Diarrhea (up to 16%), nausea, itching (up to 4%)
• Contraindications: severe renal disease (creat cl < 30 ml.min); mod. Renal
disease (creat cl 30-50-ml/min: 1-333 mg pill 3 times daily); h/o allergy to
acamprosate
• No abuse liability, hypnotic, muscle relaxant, or anxiolytic properties
• Dose: 2 g daily (2-333 mg pills three times/d)
₋ Recommended length of treatment: 1 year
• Effective in reducing relapse to alcohol use in studies leading to FDA approval
• Not effective in Project COMBINE (JAMA 2006,2008)
• *See Clinical Tools Fact Sheet for more information*
How to Select a Medication
• Disulfiram: when the patient is committed to no
further drinking; heavy consequences of relapse
• Naltrexone: for the patient who wants to cut back
or get help for craving
• Acamprosate: naltrexone doesn’t work, patient
needs opioid analgesia; disulfiram not an option
Pharmacotherapies for
Opiate Addiction
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Methadone (Can’t use outside of
Narcotic Treatment Program)
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Buprenorphine
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Naltrexone
Clinical Guidance on Use of MAT
SAMHSA Advisory: An Introduction to Extended-Release
Injectable Naltrexone for the Treatment of People with Opioid
Dependence
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http://store.samhsa.gov/product/Advisory-An-Introduction-toExtended-Release-Injectable-Naltrexone-for-the-Treatment-ofPeople-with-Opioid-Dependence/SMA12-4682
TIP 40 Center for Substance Abuse Treatment. MedicationAssisted Treatment for Opioid Addiction in Opioid Treatment
Programs.
• http://www.ncbi.nlm.nih.gov/books/NBK64164/
TIP 43 Medication Assisted Treatment for Opioid Addiction in
Opioid Treatment Programs
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http://store.samhsa.gov/product/TIP-43-Medication-AssistedTreatment-for-Opioid-Addiction-in-Opioid-TreatmentPrograms/SMA08-4214
Why do Primary Care Physicians and
Psychiatrists Need to Know about
Treating Opiate Addiction?
• Increasing use of opioids to treat chronic pain
• Published rates of abuse and/or addiction in chronic
pain populations are 3-19%; making it important to
consider in treatment using chronic opioid therapy
Fishbain et al. Clin J Pain, 1992
Rates of Prescription Pain
Medication Abuse
Nonmedical use of prescription medications (past
month, 2010): 7 million
• Opioids (4.4 million), CNS depressants,
stimulants
• Prescription pain medication misuse now
second only to marijuana
• Treatment admissions (led by addiction to
prescription pain medications): 4 fold increase
2004-2008
• 98% increase in ED visits 2004-2009
Source: NSDUH, 2009, 2011, http://www.cdc.gov/HomeandRecreationalSafety/pdf/poision-issuebrief.pdf
Source Where Pain Relievers Were Obtained for
Most Recent Nonmedical Use among Past Year
Users Aged 12 or Older: NSDUH 2010
Source Where Respondent Obtained
Bought on
Drug Dealer/ Internet
0.4%
Stranger
More than 4.4%
One Doctor
1.6%
One Doctor
17.3%
Bought/Took
from Friend/Relative
14.8%
Other 1
6.5%
Free from
Friend/Relative
55%
Source Where Friend/Relative Obtained
More than One Doctor
3.3%
Free from
Friend/Relative
7.3%
One
Doctor
79.4%
Bought/Took from
Friend/Relative
4.9%
Drug Dealer/
Stranger
1.6%
Other 1
3.5%
Note: Totals may not sum to 100% because of rounding or because suppressed estimates are not shown.
1 The Other category includes the sources: “Wrote Fake Prescription,” “Stole from Doctor’s
Office/Clinic/Hospital/Pharmacy,” and “Some Other Way.”
Why Are Opioids Being Prescribed
More Frequently?
Model Policy for the Use of Controlled Substances for the
Treatment of Pain*
• Pain management integral to medical practice
• Opioids may be necessary
• Physicians will not be sanctioned for prescribing
opioids for legitimate medical purposes
• Undertreatment of pain will be considered a deviation
from the standard of care
• Use of opioids for purposes other than analgesia
threaten individuals and society
• Physicians have a responsibility to minimize abuse and
diversion
*Federation of State Medical Boards, 2003
Challenges with Opioids for Pain
Management
Chronic opioids for non-malignant pain presents many
potential problems:
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Lack of evidence for efficacy, particularly with high dose opioid
therapy
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Syndrome of rebound pain/hyperalgesic states produced by opioid
use
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Withdrawal syndromes masquerading as “pain”
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Opioid adverse events: QT prolongation, Torsade de Pointes
(shown with methadone)
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Rate of addiction may be underestimated (e.g.: 1% of chronic pain
patients receiving opioids vs. 10% rate of SUDs for general
population)
Balantyne et al., 2003
What’s the Best Path?
Use Best Practices
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Thorough history and physical examination; get old
medical records; query previous treatments and
responses/check Prescription Monitoring Program in your
state at baseline and periodically thereafter (e.g.: every 36 months)
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Speak with family/S.O. with consent (if available)
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Diagnostic work-up
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Adequate treatment of acute or chronic pain associated
with diagnosed condition/lesion (e.g. metastatic cancer)
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Consider non-opioid options (especially in those with
substance abuse history)
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Consider Risk/Benefit of chronic opioid therapy
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Reassess frequently and modify treatment plan
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Documentation
If You Decide that Opioid Therapy for Chronic
Nonmalignant Pain is Indicated for Your Patient
Check urine drug screen initially and periodically:
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Illicit drug use highly correlated with opioid abuse/addiction
Confirm use of the drug you’re prescribing
Point of Service vs. Clinical Lab (GC/MS confirmation)
Pill Counts
Periodic review:
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Evidence of analgesia
Treat side effects
Enhanced social/employment functioning
Overall improved quality of life
Consultation
• Pain specialists
• Psychiatrist (co-occurring mental illness is common)
• Addiction specialist
Approaching Patient with Aberrant
Medication-Taking Behavior
• Take non-judgmental stance
• Use open-ended questions
• State your concerns about the behavior
₋ Is the patient more focused on specific opioid or pain relief?
• Approach as if they have a relative contraindication to
controlled drugs (if not absolute contraindication)
• Take pressure off yourself by referring to clinic policies
Passik SD, Kirsh KL. J Supportive Oncology, 2005.
What to do if Your Patient Develops a Substance
Use Disorder with Prescribed Opioids
Therapeutic Options:
1. Detoxification (medical withdrawal from opioids); short term
pharmacotherapy may occur in inpatient, residential or
outpatient settings; patients may benefit from naltrexone
following medical withdrawal as medical withdrawal alone
has high relapse rate
2. Naltrexone
3. Possible methadone maintenance (especially if
ongoing opioid analgesia needed)
4. Buprenorphine
₋ Medical withdrawal and/or medication therapies
should include psychosocial interventions, e.g.:
Individual/Group Drug Counseling
Know the options in your community
Naltrexone (Antagonist Therapy)
Why antagonist therapy?
• Block effects of a dose of opiate (Walsh et al. 1996)
• Prevent impulsive use of drug
• Relapse rates high (90%) following detoxification with no medication
treatment
• Dose (oral): 50 mg daily, 100 mg every 2 days, 150 mg every third day
• Injectable naltrexone once monthly; eliminates need for daily dose
• Who gets naltrexone?
₋ Highly motivated
₋ Does not want agonist/controlled substance
₋ Some employment requirements
Be aware and tell patients that loss of opioid tolerance occurs
with naltrexone; relapse could place patient at danger for
overdose
Agonist/Partial Agonist
Pharmacotherapy
What is agonist therapy?
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Use of a long acting medication in the same class as
the abused drug (once daily dosing)
Prevention of Withdrawal Syndrome
Induction of Tolerance
What agonist therapy is not:
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Substitution of “one addiction for another”
Opioid Dependence
Maintenance Therapy
Methadone Maintenance: Who is appropriate?
• Needs structure of daily dosing/staff evaluation
• Pain and addiction
• Co-occurring mental illness
Characteristics
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Long acting mu agonist
Duration of action: 24-36 h
Dose: philosophical issue for many programs
30-40 mg will block withdrawal, but not craving
Illicit opiate use decreases
80-120 mg is average therapeutic dose
Opioid Dependence
Maintenance Therapy
Buprenorphine
• Mu opioid receptor partial agonist
• Strong affinity for mu opioid receptors; slow to dissociate
from receptors
• Schedule III
• Little effect on respiration or cardiovascular responses at
high doses
• Induction onto medication when in mild-moderate
withdrawal
• Maintenance form: buprenorphine/naloxone combination;
except pregnant women: use mono-formulation
• Average dose 8/2-16/4 mg daily (sublingual)
Opioid Dependence
Maintenance Therapy
Buprenorphine
• Can be used for withdrawal treatment or maintenance
• Maintenance treatment more effective than withdrawal
treatment
• Mild withdrawal syndrome
• Primary care physicians, psychiatrists, addiction
specialists are expected to be providers of this treatment
• Abuse by injection may be problem in some
• Drug Interactions: Atazanavir/ritonavir: increases
buprenorphine concentrations; rifampin: decreases
buprenorphine concentrations; opiate withdrawal possible
• DEA waiver required to prescribe
Why is All of This Important?
• Drug and alcohol use disorders affect approximately 10% of
the American population
• Screening and early intervention= prevention!
• Substance use disorders are chronic, relapsing diseases
that are likely to recur
• Effective pharmacotherapies are available and can be
implemented in primary care
• Substance abuse can negatively impact other illnesses
present in the patient (e.g.: alcoholic cardiomyopathy,
COPD, HIV/AIDS, HCV, other ID)
• May masquerade as an illness that the patient does not
have (e.g.: HTN, seizure d/o, mental disorders)
• Can contribute to non-adherence to prescribed regimens,
toxicities due to drug interactions
More Information
• The PCSS-O module entitled “Review of Opioids”
will offer additional information on opioids and
medication treatments for opioid addiction
• The PCSS-O module entitled “Considerations in the
Assessment and Treatment of Pain and Opioid Use
Risk” will offer additional information on pain and
addiction
Clinical Support Systems
Sponsored by Center for Substance Abuse Treatment/SAMHSA
www.PCSSB.org
(888) 572-7724
www.PCSS-O.org
(855) 227-2276
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