Medication Assisted Treatment

Michael Palladini, RPh MBA CACpalladini.michael@gmail.com

History of MAT

Addiction as a Disease

• The concept of addiction as a disease of the brain challenges deeply ingrained values about self-determination and personal responsibility that frame drug use as a voluntary, hedonistic act. In this view, addiction results from the repetition of voluntary behaviors.

• Advances in neurobiology have begun to clarify the mechanisms underlying the profound disruptions in decision-making ability and emotional balance displayed by persons with drug addiction.

“Collaboration requires openness to the possibility that our world-view and the cherished concepts we use to describe it may need to become more subtler, more fine-grained, amended or even discarded; and, that approaches which don’t work for one person can, equally, be life-saving for others, when all the time our own beliefs, experiences, perhaps even our entire biography, shouts out that this can’t be so.”

—Neil Hunt

• Many people recover from opioid dependence without the aid of medications—both with and without the aid of alternative treatment

• No one medication has been found to be effective for all patients being treated for opioid addiction

• Patients may transition from one medication to another through the stages of their recovery

• Many patients effectively combine medications with psychosocial treatment and peer-based recovery mutual aid to support their long-term recoveries.

What distinguishes addiction from treatment of addiction with methadone or buprenorphine maintenance is the presence of:

• Impaired control

• Craving

• Preoccupation

• Compulsive use in spite of escalating consequences

MAT

• Improve survival

• Increase retention in treatment

• Decrease illicit opiate use

• Decrease HepC/HIV

• Decrease criminal activity

• Increase employment

• Improve birth outcomes

Opiates/Opioids “Traditional Pain Relievers”

• Morphine• Codeine• Diacetylmorphine (Heroin)• Oxycodone• Hydrocodone• Oxymorphone• Hydromorphone• Fentanyl• Buprenorphine• Methadone

Opioid Effects

Therapeutic Effects

• Analgesia

• Sedation/Relaxation

• Cough Suppression

• Diarrhea Cessation

Side Effects

• Nausea/Vomiting

• Dizziness

• Headache

• Constipation

• Sweating

• Pruritus

• Dry mouth

• Miosis

• Euphoria

• Respiratory Depression

PotenciesDrug Morphine Equivalency

Aspirin 1/360

Codeine 1/20

Tramadol 1/10

Hydrocodone 0.6

Oxycodone 2-3

Heroin 2-4

Methadone 3-4

Oxymorphone 7

Buprenorphine 40

Fentanyl 50-100

Sufentanyl 500-1,000

Carfentanil 10,000-100,000

Signs and Symptoms of Opioid Withdrawal

• Dysphoria /Agitation• Anxiety• Nausea or vomiting • Muscle aches• Abdominal cramps • Lacrimation• Rhinorrhea• Insomnia

• Pupillary dilation • Sweating • Gooseflesh • Diarrhea • Yawning • Tachycardia• Hypertension

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23% of all patients in addiction treatment in the United States. Although the theory of MM is based on the ideal of prolonged maintenance for most patients, only 40% of MM patients have been in MM more than two years, and most are treated for less than one year

-DASIS (2006). The DASIS Report: Facilities operating opioid treatment programs: 2005. Office of Applied Studies, Substance Abuse and Mental Health Services Administration; Kresina, T.F., Litwin, A., Marion, I., Lubran, R., & Clark, H.W. (2009). United States government oversight and regulation of medication assisted treatment for the treatment of opioid dependence. Journal of Drug Policy Analysis, 2(1), Article 2.

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Comprehensive Addiction and Recovery Act (CARA) of 2014

• Expand prevention and educational efforts—particularly aimed at teens, parents and other caretakers, and aging populations—to prevent the abuse of opioids and heroin and to promote treatment and recovery.

• Expand the availability of naloxone to law enforcement agencies and other first responders to help in the reversal of overdoses to save lives.

• Expand resources to identify and treat incarcerated individuals suffering from addiction disorders promptly by collaborating with criminal justice stakeholders and by providing evidence-based treatment.

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Comprehensive Addiction and Recovery Act (CARA) of 2014

• Expand disposal sites for unwanted prescription medications to keep them out of the hands of our children and adolescents.

• Launch an evidence-based opioid and heroin treatment and interventions program. While we have medications that can help treat addiction, there is a critical need to get the training and resources necessary to expand treatment best practices throughout the country.

• Strengthen prescription drug monitoring programs to help states monitor and track prescription drug diversion and to help at-risk individuals access services.

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US Attorneys Working Group on Drug Overdose and Addiction

September 2014

Recommendations:

• Educate buprenorphine providers on the best practice guidelines

• Develop and educate probation officers and state law enforcement about addiction and MAT

• Increase the number of drug and alcohol assessments and referrals to MAT for people who are incarcerated or on probation

CMS’s Opioid Misuse Strategy

• The CMS effort includes four priority areas: • 1. Implement more effective person-centered and

population-based strategies to reduce the risk of opioid use disorders, overdoses, inappropriate prescribing, and drug diversion;

• 2. Expand naloxone use, distribution, and access, when clinically appropriate;

• 3. Expand screening, diagnosis, and treatment of opioid use disorders, with an emphasis on increasing access to medication-assisted treatment; and

• 4. Increase the use of evidence-based practices for acute and chronic pain management.

Oxycontin“Abuse-deterrent formulations”

Fentanyl and Analogues

• Sublimaze® in the 1960’s• Duragesic® in the 1990’s• Actiq® lollipop, Fentora® buccal tablet (also a

sublingual spray)• AMF (alpha-methylfentanyl)• 3MF (3-methylfentanyl)• Acetylfentanyl• Carfentanil• Cyclopentylfentanyl• Others

Molecular Analogues/Synthetics

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Fentanyl

Carfentanil

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Fentanyl2mg can be lethal(2000 mcg)

Carfentanil can be 1,000 x potency

That’s 2 mcg

0.000000075 ozs

“A kilogram of heroin may in fact return a profit of about $80,000. A kilogram of Fentanyl may in fact return a profit of over $1 million.”

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Medication Assisted Treatment (MAT)

Methadone

Buprenorphine

Naltrexone

MAT

• Suppress symptoms of withdrawal• Decrease illicit opiate cravings and use• Block effects of other opiates• Improve survival• Increase retention in treatment• Decrease Hep C and HIV • Decrease criminal activity• Increase employment• Improve birth outcomes

Medications1) Physiological effects2) Legal and Regulatory

Choice of Therapy:Detox

-Withdrawal Symptom Control-Retention

Rehab/Maintenance-Reduction of Cravings-Retention-Convenience/Cost

Principles

• Informed Consent

• Psychosocial Care

• Physical and Mental Health Needs

-Pain

-Medications

Screening for MAT

• Opioid Dependence (DSM)

• Psych History (compliance)

• Medical History

• Pregnancy

• Recovery Supports

• Treatment History

Methadone

• Synthetic opioid

• Generic formulation only on market

• “Full agonist action”

• Use in opioid dependence circa 1965

• Narcotic Addict Treatment Act of 1974

• Considerable federal and state regulations

Methadone Induction

• First dose through 2 weeks

• 10 - 30mg/day (physician determined)

-Reassessed at 2 – 4 hours

-5 – 10mg increase possible

• Peak period (max concentration) approx. 3 to 4 hours after dose

-Clients asked about symptoms daily

Methadone Stabilization

• Weeks 3 – 4 of treatment

• Early stabilization includes stable dose for 3 to 4 consecutive days.

• Dose adjustment by 5 – 10mg every 3 to 5 days

• Late stabilization should occur after approximately 4 to 5 weeks.

• Maintenance dose allows for no withdrawal symptoms, no intoxication

Methadone Issues

• Abuse/Diversion/Overdose

Use of other drugs

-Opiates/Cocaine/Benzodiazepines

• Drug Interactions

-Significant

• Dosing Issues

-Complex/Extensive Metabolism

-Prolonged Withdrawal/Tapering

Buprenorphine

• DATA 2000

• Semi synthetic opioid

• “Partial agonist action”

• The “DEA physician waiver”

Buprenorphine “Ceiling Effect”

Formulations

• Suboxone® Film (4:1 ratio)

12mg buprenorphine/3mg naloxone

8mg buprenorphine/2mg naloxone

4mg buprenorphine/1mg naloxone

2mg buprenorphine/0.5mg naloxone

• Buprenorphine Tablet (Mono product, formerly Subutex®)

8mg buprenorphine

2mg buprenorphine

Formulations (cont)

• Zubsolv tablet (4:1 ratio)1.4mg buprenorphine/0.36mg naloxone2.9mg buprenorphine/0.71mg naloxone5.7mg buprenorphine/1.4mg naloxone8.6mg buprenorphine/2.1mg naloxone• Bunavail buccal film (6:1 ratio)2.1mg buprenorphine/0.3mg naloxone4.2mg buprenorphine/0.7mg naloxone6.3mg buprenorphine/1mg naloxone

Buprenorphine Candidates

• Mild to moderate opiate dependence

• Methadone inappropriate

• Adequate support

• Age > 16

• Co-occurring MH stability

• Not suicidal

• Not using CNS depressants

• Motivated for treatment

Induction/Stabilization/MaintenanceTapering

• Dosing is specific to individual, management of cravings and withdrawal symptoms

• Effective treatment generally accomplished with a dosing regimen 8 – 24mg daily

• Daily dosing can be reduced over time without a loss of clinical effectiveness

Induction

• Typically one week in duration

• Patient must present with objective signs of withdrawal (avoid precipitated wd)

• Day 2 Max Dose usually between 8 – 16mg

• Methadone conversion:

-30mg (or lower) daily methadone dose for 5 – 7 days, then

-Abstain from methadone 48 – 72 hours

Induction (cont)

• Non-opioid tolerant patients:

-initiate treatment with no more than 2mg daily

-Increase dose slowly, 2mg every 5 – 7 days

• Patients using illicit buprenorphine:

-UDS

-Start with 8 – 12mg daily dosage

Stabilization

• Usually 1 – 2 months in duration

-No withdrawal symptoms

-Minimal side effects

-Minimal cravings

• Dosage adjustments should be in 2 – 4 mg increments/weekly

• Dosing schedule adjustable

• UDS

• On site dosing

Maintenance

• 18 – 24 months (individual dependent)

• Varying Prescription lengths (up to 1 month)

• UDS

• Bio – Psycho - Social Stability

Tapering

“Individualized”

-Express a desire to DC

-Stable housing/income

-Adequate support

-Agree to conditions of termination

Melted Suboxone film

Buprenorphine Issues

• Abuse/Diversion/Overdose• Dosing Issues

-Complex/Extensive Metabolism-Prolonged Withdrawal/Tapering

• Treatment/Counseling issues-DATA 2000 requirements-Payer requirements

• Drug Interactions

Suboxone vs Subutex

• Both Suboxone and Subutex cause precipitated withdrawal, which comes from buprenorphine, not naloxone.

• Naloxone does not pass through the mucous membranes lining the oral cavity, and instead ends up being swallowed, and taken up into the portal vein from the proximal small intestine.

• In MOST people, naloxone is then rapidly destroyed by the liver before getting into the systemic circulation.

• In a FEW people, though, naloxone causes side effects. Side effects are of two basic types.

• The first type is an allergic reaction to naloxone, causing flushing, wheezing, and perhaps nausea, vomiting, and/or rash

• The second type is where the naloxone is not destroyed well be the liver and instead gets into the systemic circulation and then to the brain and spinal cord, where it blocks the opiate effects of buprenorphine.

Naltrexone

• Synthetic molecule

• “Antagonist action”

• FDA original approval for opioid dependence 1984

• FDA approved for alcohol dependence 1994

• Vivitrol® FDA approved in 2006 (alcohol),

2010 (opioid)

Naltrexone

• Non-scheduled medication

• Vivitrol® (Alkermes)

• 380mg IM q28 days

• 7-10 days opiate free period

Naltrexone Issues

• Vulnerability to opioid overdose

• Precipitation of opioid withdrawal

• Switching from agonist therapy

• Cost

MAT Issues/Questions/Concerns

• Harm Reduction vs. Drug Free Models

• “Treatment” part of MAT

• Diversion

• Tapering/Detox

• Drug Interactions

• Profit Motives

• Long Term Effects

• Lack of Data