Using Buprenorphine in an Opioid Treatment Program Thomas E. Freese, PhD Director of Training, UCLA Integrated Substance Abuse Programs Director, Pacific Southwest Addiction Technology Transfer Center Adj Assoc Professor, Dept of Psychiatry, UCLA David Geffen School of Medicine
Bringing Buprenorphine into the Opiod Treatment System 1906 Pure Food and Drug Act: Prevents manufacture, sale, or transportation of adulterated/misbranded/poisonous/ deleterious foods, drugs, medicines, and liquors. 1909 Smoking Opium Exclusion Act: Banned the import, possession and use of "smoking opium". Did not regulate opium-based "medications". 1919 Supreme Court ruled that doctors may not prescribe maintenance supplies of narcotics to people addicted to narcotics. However, it did not prohibit doctors from prescribing narcotics for withdrawal. 1924 Heroin Act: Prohibited manufacture, importat and possession of heroin. 1932 -- Uniform State Narcotic Act: Encouraged states to pass laws matching the Narcotic Drug Import and Export Act. 2
Bringing Buprenorphine into the Opioid Treatment System 1938 -- Food, Drug, and Cosmetic Act: manufacturer has to prove to FDA that a drug were safe before it could be sold 1970 -- Controlled Substance Act: Schedules substances based on the medicinal value, harmfulness, and potential for abuse or addiction. 1973 Drug Enforcement Agency was formed 1974 Narcotic Addict Treatment Act of 1974: Registration of practitioners conducting narcotic treatment programs, aka methadone clinics. 2000 The Drug Addiction Treatment Act of 2000: Enables qualified physicians to prescribe/dispense narcotics for the purpose of treating opioid dependency. 2002-- DEA reschedules buprenorphine as schedule III drug. 3
Drug Addiction Treatment Act of 2000 (DATA 2000) Expands treatment options to include both the general health care system and opioid treatment programs. Expands number of available treatment slots Allows opioid treatment in office settings Sets physician qualifications for prescribing the medication
Physicians must: DATA 2000: Physician Qualifications Be licensed to practice by his/her state Have the capacity to refer patients for psychosocial treatment Limit number of patients receiving buprenorphine to 30 patients for a least the first year File for a new waiver after first year to increase their limit to 100 patients. Be qualified to provide buprenorphine and receive a license waiver
Approval of Buprenorphine and Buprenorphine/Naloxone (SAMHSA, 2006)
Buprenorphine Research Outcomes Buprenorphine is as effective as moderate doses of methadone (Fischer et al., 1999; Johnson, Jaffee, Fudula,. 1992; Ling et al., 1996; Schottenfield et al., 1997; Strain et al., 1994). Buprenorphine is as effective as moderate doses of LAAM (Johnson et al., 2000). Buprenorphine's partial agonist effects make it mildly reinforcing, encouraging medication compliance (Ling et al., 1998). After a year of buprenorphine plus counseling, 75% of patients retained in treatment compared to 0% in a placebo-pluscounseling condition (Kakko et al., 2003).
Buprenorphine as a Treatment for Opioid Addiction A synthetic opioid Described as a mixed opioid agonistantagonist (or partial agonist) Available for use by certified physicians outside traditionally licensed opioid treatment programs
Advantages of Buprenorphine in the Treatment of Opioid Addiction 1. Patient can participate fully in treatment activities and other activities of daily living easing their transition into the treatment environment 2. Limited potential for overdose (Johnson et.al, 2003) 3. Minimal subjective effects (e.g., sedation) following a dose 4. Available for use in an office setting 5. Lower level of physical dependence
Disadvantages of Buprenorphine in the Treatment of Opioid Addiction 1. Greater medication cost 2. Lower level of physical dependence (i.e., patients can discontinue treatment) 3. Detectable only in specific urine toxicology screenings
Why was Buprenorphine/Naloxone Combination Developed? Developed in response to increased reports of buprenorphine abuse outside of the U.S. The combination tablet is specifically designed to decrease buprenorphine abuse by injection, especially by out of treatment opioid users.
What is the Ratio of Buprenorphine to Naloxone in the Combination Tablet? Each tablet contains buprenorphine and naloxone in a 4:1 ratio Each 8 mg tablet contains 2 mg of naloxone Each 2 mg tablet contains 0.5 mg of naloxone Ratio was deemed optimal in clinical studies Preserves buprenorphine s therapeutic effects when taken as intended sublingually Sufficient dysphoric effects occur if injected by some physically dependent persons to discourage abuse
Why Combining Buprenorphine and Naloxone Sublingually Works Buprenorphine and naloxone have different sublingual (SL) to injection potency profiles that are optimal for use in a combination product. SL Bioavailability Buprenorphine 40-60% Naloxone 10% or less Potency Buprenorphine 2:1 Naloxone 15:1 (Chaing & Hawks, 2003)
Buprenorphine/Naloxone: What You Need to Know Basic pharmacology, pharmacokinetics, and efficacy is the same as buprenorphine alone Partial opioid agonist; ceiling effect at higher doses Blocks effects of other agonists Binds strongly to opioid receptor, long acting
Quality of Life in Methadone and Buprenorphine Patients 213 participants 106 on Buprenorphine 107 on Methadone Enrolled after being in treatment for 3 months Evaluated at 12 months for improvements in Opioid use Psychiatric status Quality of life Significant improvements overall. No group difference Maremmani, et al., (2006), JSAT, 33, 91-98. Slide 15
Comparing Buprenorphine to Methadone Mortality over 9 months 25 Methadone = 13,718 clients (60 deaths) 25 Buprenorphine = 2,716 (7 deaths) 20 20 15 15 10 10 5 5 0 0 Not in Tx In Tx Not in Tx Bell, et al., (2009), Drug and Alcohol Dependence, 104, 73-77. In Tx Slide 16
Use in OTPs 17
Selecting OTP vs OBOT No good data on which to make a selection. Methadone retains people in treatment better Buprenorphine has a better safety profile Must consider patient preference Patient s ability to manage meds responisbly Need for structure in treatment (OTPs provide more) Specific drug being treated and route of admin Psychiatric co-morbidity Cost and coverage http://atforum.com/2013/11/methadone-vs-buprenorphine-howdo-otps-and-patients-make-the-choice/ 18
Buprenorphine in OTPs Originally, bup must be dispensed just like methadone in OTPs (i.e. on site dosing until patient earns take homes) Physicians had a 100 pt cap, but could give take homes right away 19
OTPs providing buprenorphine 0-5 6-10 11-30 31-50 51-70 > 71
A Quick Review of the Medication Itself 21
Partial Opioid Agonist Buprenorphine Has effects of typical opioid agonists at lower doses Produces a ceiling effect at higher doses Binds to opioid receptors and is long-acting Safe and effective therapy for opioid maintenance and detoxification in adults Slow to dissociate from receptors so effects last even if one daily dose is missed. FDA approved for use with opioid dependent persons aged 16 and older 22
Formulations of Buprenorphine Buprenorphine is currently marketed for opioid treatment under the trade names: Subutex (buprenorphine) Suboxone (buprenorphine/naloxone) Over 25 years of research Over 5,000 individuals received medication during clinical trials Proven safe and effective for the treatment of opioid addiction 23
Newer Formulations of Buprenorphine In response to reports of diversion and non-prescribed use of buprenorphine tablets, three new formulations have been approved or are in late stages of development: Suboxone Sublingual Film (approved) Still in trials (i.e., not FDA approved) Long-acting injectable rod (Probuphine) Treatment of opioid dependence Patch (Butrans) 7 days of medication delivered Treatment of pain 24
Buprenorphine Research Outcomes Buprenorphine is as effective as moderate doses of methadone (Fischer et al., 1999; Johnson, Jaffee, &Fudula, 1992; Ling et al., 1996; Schottenfield et al., 1997; Strain et al., 1994). Buprenorphine is as effective as moderate doses of LAAM (Johnson et al., 2000). Buprenorphine's partial agonist effects make it mildly reinforcing, encouraging medication compliance (Ling et al., 1998). After a year of buprenorphine plus counseling, 75% of patients retained in treatment compared to 0% in a placebo-plus-counseling condition (Kakko et al., 2003). 25
Buprenorphine Diversion 26
Discontinuation of Sale and Distribution of Subutex In Sept 2011, Reckitt Benckiser issued a letter to notify health care providers that they were discontinuing the sale and distribution of Subutex Tablets CIII (2mg and 8mg tablets), as of January 2012 Believe the mono product creates a greater risk of misuse, abuse, and diversion Concentrating future efforts around less abusable products to protect patients, communities, and access to treatment 27
U.S. Retail Distribution of Buprenorphine Approaches 1.5 million Grams 1,600,000 1,400,000 1,200,000 1,000,000 800,000 600,000 400,000 200,000 0 2003 2004 2005 2006 2007 2008 2009 2010 SOURCE: CESAR FAX, Volume 20, Issue 23, June 20, 2011. 28
Buprenorphine Now More Likely Than Methadone to Be Found in Drug Seizures 12,000 10,000 8,000 6,901 Methadone 8,221 7,539 9,202 9,136 10,016 7,508 10,537 9,477 6,000 5,719 4,961 Buprenorphine 4,000 2,000 0 2,855 1,537 90 360 792 2003 2004 2005 2006 2007 2008 2009 2010 SOURCE: CESAR FAX, Vol. 21, Issue 13, April 2, 2012. 29
Law Enforcement Seizures of Buprenorphine (NFLIS) 4,500 4,000 3,500 3,000 2,500 2,000 1,500 1,000 500 0 4,161 3,856 1,689 831 2003 2004 2005 2006 2007 2008 2009 2010 Northeast South Midwest West SOURCE: CESAR FAX, Vol. 21, Issue 14, April 9, 2012. 30
Strategies to Reduce Diversion and Misuse Clear expectations for doctor and patient Open discussion of misuse and diversion Therapeutic dosing and in-office induction Encourage safe storage Frequent office visits until patient is stable SOURCE: Slide courtesy of Michelle Lofwall, MD. 35
Notice: The Drug Addiction Treatment Act of 2000 limits physicians or physician group practices to prescribing buprenorphine for opioid addiction to a maximum of 100 patients at one time. Because of this, some physicians listed on the Locator may not be accepting new patients at this time. If you are unable to find a physician within your area who is accepting new patients, please check our site later, as new physicians are being added weekly. To locate the physicians) authorized to prescribe Buprenorphine nearest you, find your State on the map below and click on it. www.buprenorphine.samhsa.gov
Resources for Continued Learning TIP 40: Clinical Guidelines for the Use of Buprenorphine in the Treatment of Opioid Addiction SAMHSA s Buprenorphine Website (http://buprenorphine.samhsa.gov) Physician Clinical Support System-Buprenorphine (www.pcssb.org) BupPractice Training and Practice Tools www.buppractice.com) 43
Feel free to contact me with questions or for additional information: Thomas E. Freese, PhD tfreese@mednet.ucla.edu www.psattc.org 44