Medication Assisted Treatment Michael Palladini, RPh MBA CAC palladini.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 selfdetermination 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 finegrained, 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
Potencies Drug 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 11
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. 14
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. 15
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 Abusedeterrent 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 Fentanyl Carfentanil 20
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Fentanyl 2mg 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. 22
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
Medications 1) Physiological effects 2) 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 naloxone 2.9mg buprenorphine/0.71mg naloxone 5.7mg buprenorphine/1.4mg naloxone 8.6mg buprenorphine/2.1mg naloxone Bunavail buccal film (6:1 ratio) 2.1mg buprenorphine/0.3mg naloxone 4.2mg buprenorphine/0.7mg naloxone 6.3mg 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/Maintenance Tapering 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