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The effectiveness of buprenorphine in treating opioid addiction Skylee Campbell Outline 1. Background 2. Opioid vs opiate 3. Brief history 4. Treatment 5. Conclusions Opioid Statistics 1. 2. 3. 4. 5. Increased abuse of prescription opioids and non-medical opioids Increase in Admission rate to substance abuse treatment programs Opioid-related overdose Opioid-induced mortality Wu, Woody, Yang and Blazer (2010) Background Opioid vs opiate Brief history Treatment Conclusions 1. 2. 3. 4. 5. Background Opioid vs opiate Brief history Treatment Conclusions Increased Mortality Rates 3 main factors: (1) Direct effects on health e.g., cardiac arrhythmias, respiratory failure (2) Indirect effects via exposure e.g., non-sterile injection equipment (3) Environmental factors e.g., suicide, advanced exposure to violence, poor lifestyle choices, accidents Hulse, English, Milne, & Holman (1999) Opioid Statistics 1. 2. 3. 4. 5. Background Opioid vs opiate Brief history Treatment Conclusions Highest misused drugs in the United States Lifetime prevalence: 1.7 % of every 19-30 year old has tried heroin 18.7 % have used other opioids (such as Vicodin and OxyContin) Wu, Woody, Yang, & Blazer (2010) Veilleux, Colvin, Anderson, York & Heinz (2009) Younger Generations 1. 2. 3. 4. 5. Background Opioid vs opiate Brief history Treatment Conclusions Increase in non-medical prescription opioids Average age is 21.2 Most popular prescription drug is Vicodin Veilleux, Colvin, Anderson, York, & Heinz (2009) 1. 2. 3. 4. 5. Location Prescription drugs: more in urban areas rather than large cities and rural Possible reasons: - Heroin not as available as prescription drugs - Prescription drugs more socially acceptable - Easier to attain and cheaper Cicero, Surratt, & Inciardi, (2007) Background Opioid vs opiate Brief history Treatment Conclusions Gender Differences 1. 2. 3. 4. 5. Background Opioid vs. opiate Brief history Treatment Conclusions Women are more likely than men to: - initiate opioid use via prescription opioids - use for indicated use - Less likely to seek treatment for an opioid use disorder McHugh, DeVito, Dodd, Carroll, Potter, Greenfield, Connery & Weiss, (2013) Opiate vs. Opioid 1. 2. 3. 4. 5. Background Opioid vs opiate Brief history Treatment Conclusions Opiate Natural origin, made from opium (Papaver somniferum) Examples - Morphine - Codeine - Thebaine Renner & Levounis (2011) Opiate vs. Opioid 1. 2. 3. 4. 5. Background Opioid vs opiate Brief history Treatment Conclusions Opioid Opiate-like drugs Basic subgroups (1) Semisynthetic e.g., heroin, oxycodone, and buprenorphine (2) Synthetic: e.g., methadone and other medical prescription drugs in opioid group Renner & Levounis (2011) Abuse Potential 1. 2. 3. 4. 5. Background Opioid vs opiate Brief history Treatment Conclusions Many opiates and opioids have a high abuse potential A drug will have a higher abuse potential if: - Route of administration is quicker Injection > Oral - Shorter half-life e.g., Heroin vs. Methadone - Higher lipophilic properties Faster route across blood-brain barrier Renner & Levounis (2011) History 1. 2. 3. 4. 5. Background Opioid vs opiate Brief history Treatment Conclusions Opium - Produced from poppy: Papaver somniferum - 10 % morphine, 0.5 % codeine, lower % of thebaine McKim & Hancock (2013) History of Opium 1. 2. 3. 4. 5. Background Opioid vs opiate Brief history Treatment Conclusions 6th millenium BCE in the Western Mediterranean region Written reference to opium “joy plant” Spread to Middle East, North Africa, India, and China Primarily used as medicine, BUT also mentioned non-medical, more enjoyable properties McKim & Hancock (2013) History 1. 2. 3. 4. 5. Background Opioid vs opiate Brief history Treatment Conclusions Opiate: Morphine Frederick Serturner Isolated morphine from opium 1830s: Manufactured and sold commercially Raise for concern when people became addicted Too available McKim & Hancock (2013) History 1. 2. 3. 4. 5. Background Opioid vs opiate Brief history Treatment Conclusions Opiate: Codeine Pierre J. Robiquet Used new process of isolating morphine Discovered codeine Prescription currently legal in U.S. McKim & Hancock (2013) History Opiate: Thebaine Not used for therapeutic purposes Used for semisynthetic opioids Examples - Percocet - Percodan - OxyContin (oxycodone) McKim & Hancock (2013) 1. 2. 3. 4. 5. Background Opioid vs opiate Brief history Treatment Conclusions History 1. 2. 3. 4. 5. Background Opioid vs opiate Brief history Treatment Conclusions Opioid: Heroin Discovered in 1874 as first semisynthetic form of opioid More lipid soluble than morphine Originally seen as not as addictive McKim & Hancock (2013) Treatment Considerations Mu receptor Full agonist Antagonists Partial agonist Renner & Levounis (2011) 1. 2. 3. 4. 5. Background Opioid vs. opiate Brief history Treatment Conclusions Treatment Considerations Full Agonist • Prescription opioids • Morphine • Heroin • Methadone Renner & Levounis (2011) 1. 2. 3. 4. 5. Background Opioid vs. opiate Brief history Treatment Conclusions Treatment Considerations Antagonist • Do not produce any opioid effects • Naloxone: - Reverses effects of opioids • Naltrexone: - Blocks agonist from binding to mu receptor Renner & Levounis (2011) 1. 2. 3. 4. 5. Background Opioid vs. opiate Brief history Treatment Conclusions Treatment Considerations 1. 2. 3. 4. 5. Background Opioid vs. opiate Brief history Treatment Conclusions Partial Agonist • Buprenorphine - Longer half-life - Can relieve opioid and opiate withdrawal symptoms Renner & Levounis (2011) Buprenorphine 1. 2. 3. 4. 5. Background Opioid vs. opiate Brief history Treatment Conclusions Originally developed in the 1970s Developed because - Opioid addiction is costly to the government - Methadone treatment had many associated limitations Renner & Levounis (2011) Buprenorphine Administration Routes (1) Subutex form • Administered orally • Buprenorphine alone (2) Suboxone form • Administered orally • Mix of buprenorphine/naloxone (3) Implants (4) Injections Renner & Levounis (2011) 1. 2. 3. 4. 5. Background Opioid vs. opiate Brief history Treatment Conclusions Buprenorphine Implants 1. 2. 3. 4. 5. Background Opioid vs. opiate Brief history Treatment Conclusions • Implant = polymetric matrix composed of ethylene vinyl acetate and buprenorphine • Advantages (1) Delivers buprenorphine over 6 months - Initial pulse release constant, low level of buprenorphine released (2) To address problems with adherence and nonmedical use (Ling, Casadonte, Bigelow, Kampman, Patkar, Bailey, Rosenthal & Beebe, 2010) Buprenorphine Injections 1. 2. 3. 4. 5. Background Opioid vs. opiate Brief history Treatment Conclusions Produces a gradual release of buprenorphine Advantages Gradual opioid detoxification with minimal withdrawal symptoms Reduces frequency of clinic visits Eliminates need for take-home medication (Sigmon, Wong, Chausmer, Liebson & Bigelow, 2004) Buprenorphine naloxone 1. 2. 3. 4. 5. Background Opioid vs. opiate Brief history Treatment Conclusions Adding naloxone discourages parenteral use BUT preserves the therapeutic effect on opiate addiction when used sublingually as intended (Harris, Jones, Welm, Upton, Lin & Mendelson, 2000) Gender Differences 1. 2. 3. 4. 5. Background Opioid vs. opiate Brief history Treatment Conclusions • No significant gender differences in treatment outcome indicators including: • Maximum daily dose of buprenorphine–naloxone • Achievement of a successful opioid treatment outcome • Treatment retention (Kelly, Schwartz, O'Grady, Mitchell, Reisinger, Peterson, Agar & Barry, 2009) Conclusions Advantages of Buprenorphine • Partial agonist • Improved overall safety margin • Long-lasting effect • Reduces severity of withdrawal Renner & Levounis (2011) 1. 2. 3. 4. 5. Background Opioid vs. opiate Brief history Treatment Conclusions Conclusions 1. 2. 3. 4. 5. Disadavantages of Buprenorphine • Concern of abuse • Need to be aware of potential for abuse Cicero, Surratt, Inciardi, & Munoz (2007) Background Opioid vs. opiate Brief history Treatment Conclusions “Holy Grail of Opioid Research” 1. 2. 3. 4. 5. Background Opioid vs. opiate Brief history Treatment Conclusions STILL in search for drug that has same analgesic effects of morphine but does NOT have side effects such as addiction Developed thousands of new opioids All have addictive properties Have NOT found perfect drug McKim & Hancock (2013) Acknowledgments • Conference organizers • Behavioral Science Department • Drs. David Yells and Richard Nance • Dr. Claudia Lieberwirth References Cicero, T. J., Surratt, H. L., & Inciardi, J. (2007). Use and misuse of buprenorphine in the management of opioid addiction. Journal of Opioid Management , 3(6), 1-7. Harris, D. S., Jones, R. T., Welm, S., Upton, R. A., Lin, E., & Mendelson, J. (2000). Buprenorphine and naloxone co-administration in opiate-dependent patients stabilized on sublingual buprenorphine. Drug and Alcohol Dependence, 61, 85-94. doi: S0376-8716(00)00126-5 McHugh, R. K., DeVito, E. E., Dodd, D., Carroll, K. M., Potter, J. S., Greenfield, S. F., Connery, H. S., & Weiss, R. D. (2013). Gender differences in a clinical trial for prescription opioid dependence. Journal of Substance Abuse Treatment, 45, 38-43. Retrieved from http://dx.doi.org/10.1016/j.jsat.2012.12.007 Hulse, G. K., English, D. R., Milne, E., & Holman, C. D. J. (1999). The quantification of mortality resulting from the regular use of illicit opiates. Society for the Study of Addiction and Other Drugs, 94(2), 221-229. doi: 0965-2140/99/020221-09 Kelly, S. M., Schwartz, R. P., O'Grady, K. E., Mitchell, S. G., Reisinger, H. S., Peterson, J. A., Agar, M. H., & Barry, B. S. (2009). Gender differences among in- and out-oftreatment opioid-addicted individuals. The American Journal of Drug and Alcohol Abuse, 35, 38-42. doi: 10.1080/00952990802342915 References Ling, W., Casadonte, P., Bigelow, G., Kampman, K. M., Patkar, A., Bailey, G. L., Rosenthal, R. N., & Beebe, K. L. (2010). Buprenorphine implants for treatment of opioid dependence: A randomized controlled trial. American Medical Association, 304(14), 1576-1582. Retrieved from http://jama.jamanetwork.com/ McKim, W. A., & Hancock, S. D. (2013). Drugs and behavior: An introduction to behavioral pharmacology. (7th ed., pp. 255-276). New Jersey: Pearson.) Renner, J. A., & Levounis, P. (2011). Handbook of office-based buprenorphine treatment of opioid dependence. (1st ed.). Virginia: American Psychiatric Publishing, Inc. Sigmon, S. C., Wong, C. J., Chausmer, A. L., Liebson, I. A., & Bigelow, G. E. (2004). Evaluation of an injection depot formulation of buprenorphine: placebo comparison. Society for the Study of Addiction, 99, 1439-1449. doi: 10.1111/j.1360-0443.2004.00834.x Veilleux, J. C., Colvin, P. J., Anderson, J., York, C., & Heinz, A. J. (2010). A review of opioid dependence treatment: Pharmacological and psychosocial interventions to treat opioid addiction. Clinical Psychology Review, 30, 155-166. doi: 10.1016/j.cpr.2009.10.006 Wu, L., Woody, G. E., Yang, C., & Blazer, D. G. (2010). Subtypes of nonmedical opioid users: Results from the national epidemiologic survey on alcohol and related conditions. Drug and Alcohol Dependence, 112, 69-80. doi: 10.1016/j.drugalcdep.2010.013 Questions?