Medication Assisted Treatment for Substance Use Disorders in

Primary Care

Elinore F. McCance-Katz, MD, PhDProfessor 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?

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 DrugsAlcohol and Illicit Drugs

1.7%1.1%

Problem Substance Use is Prevalent in Americans

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:₋ 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

• 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:₋ Those with medical contraindications₋ Those smoking fewer than 10 cigarettes/d₋ Pregnant/breastfeeding women₋ Adolescents₋ Smokeless tobacco users

Consider risk/benefit

Cigarette SmokingFDA approved:

• Nicotine Substitution (Agonist Therapy)₋ Nicotine gum₋ Nicotine lozenge₋ Nicotine patch₋ Nicotine nasal spray₋ Nicotine inhaler

• Bupropion (approved for treatment of depression and smoking cessation)

• Varenicline (nicotine partial agonist)

Cigarette SmokingNicotine gum:

• 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 SmokingNicotine gum

• 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 SmokingNicotine 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 SmokingNicotine 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

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

₋ 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

₋ 7 mg, box (14 patches) = $37₋ 14 mg, box = $47 ₋ 21 mg, box = $48

Cigarette Smoking

Cigarette SmokingNicotine 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 SmokingBupropion

• 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 SmokingVarenicline

• 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:• TIP 49 Incorporating Alcohol Pharmacotherapies into Medical Practice

• http://store.samhsa.gov/product/TIP-49-Incorporating-Alcohol-Pharmacotherapies-Into-Medical-Practice/SMA09-4380

• SAMHSA Advisory: Naltrexone for Extended Release Injectable Suspension for Treatment of Alcohol Dependence

• 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₋ may have additive hepatic effects

₋ Common AEs: nausea/headache

VA/DoD CPG SUDs, www.oqp.med.va.gov/cpg/SUD/SUD_Vase.htm

Disulfiram• 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)

• Antabuse reaction: flushing, weakness, nausea, tachycardia, hypotension ₋ Treatment of alcohol/disulfiram reaction is supportive (fluids,

oxygen)

• Side Effects: ₋ Common: metallic taste, sulfur-like odor ₋ Rare: hepatotoxicity, neuropathy, psychosis

• Contraindications: cardiac disease, esophageal varices, pregnancy, impulsivity, psychotic disorders, severe cardiovascular, respiratory, or renal disease, severe hepatic dysfunction: transaminases > 3x upper level of normal

• Avoid alcohol and alcohol containing foods

• Clinical Dose: 250 mg daily (range: 125-500 mg/d)

• 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

• Methadone (Can’t use outside of Narcotic Treatment Program)

• Buprenorphine

• Naltrexone

Clinical Guidance on Use of MATSAMHSA Advisory: An Introduction to Extended-Release Injectable Naltrexone for the Treatment of People with OpioidDependence

• http://store.samhsa.gov/product/Advisory-An-Introduction-to-Extended-Release-Injectable-Naltrexone-for-the-Treatment-of-People-with-Opioid-Dependence/SMA12-4682

TIP 40 Center for Substance Abuse Treatment. Medication-Assisted 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

• http://store.samhsa.gov/product/TIP-43-Medication-Assisted-Treatment-for-Opioid-Addiction-in-Opioid-Treatment-Programs/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-issue-brief.pdf

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.”

Bought/Took from Friend/Relative

14.8%

Drug Dealer/Stranger

4.4%

Bought on Internet

0.4% Other 1

6.5%

Free from Friend/Relative

7.3%

Bought/Took fromFriend/Relative

4.9%

OneDoctor79.4%

Drug Dealer/Stranger

1.6%Other 1

3.5%

Source Where Respondent Obtained

Source Where Friend/Relative Obtained

One Doctor17.3%

More than One Doctor

1.6%Free from

Friend/Relative55%

More than One Doctor3.3%

Source Where Pain Relievers Were Obtained for Most Recent Nonmedical Use among Past Year

Users Aged 12 or Older: NSDUH 2010

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

Why Are Opioids Being Prescribed More Frequently?

Chronic opioids for non-malignant pain presents many potential problems:

• Lack of evidence for efficacy, particularly with high dose opioid therapy

• Syndrome of rebound pain/hyperalgesic states produced by opioid use

• Withdrawal syndromes masquerading as “pain”

• Opioid adverse events: QT prolongation, Torsade de Pointes (shown with methadone)

• 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

Challenges with Opioids for Pain Management

What’s the Best Path?Use Best Practices

• 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 3-6 months)

• Speak with family/S.O. with consent (if available)• Diagnostic work-up• Adequate treatment of acute or chronic pain associated

with diagnosed condition/lesion (e.g. metastatic cancer)• Consider non-opioid options (especially in those with

substance abuse history)• Consider Risk/Benefit of chronic opioid therapy• Reassess frequently and modify treatment plan• Documentation

If You Decide that Opioid Therapy for Chronic Nonmalignant Pain is Indicated for Your Patient

Check urine drug screen initially and periodically:• 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:• 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

• 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.

Approaching Patient with Aberrant Medication-Taking Behavior

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. Naltrexone3. 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?• 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: • 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• 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

Ask a clinical question…

• Get a response from an expert PCSS mentor• Download clinical tools, helpful forms and concise guidance's (FAQs) on

specific questions regarding opioid dependence, use of buprenorphine, safe/effective use of opioids; information on training and peer support

Clinical Support SystemsSponsored by Center for Substance Abuse Treatment/SAMHSA

www.PCSSB.org(888) 572-7724

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