The effectiveness of buprenorphine in treating opioid addiction

1. The effectiveness of buprenorphine in treating opioid addiction • Skylee Campbell

2. Outline • Background • Opioid vs opiate • Brief history • Treatment • Conclusions

3. Opioid Statistics • Background • Opioid vs opiate • Brief history • Treatment • Conclusions • 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)

4. Increased Mortality Rates • Background • Opioid vs opiate • Brief history • Treatment • Conclusions • 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)

5. Opioid Statistics • 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)

6. Younger Generations • 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)

7. Location • Background • Opioid vs opiate • Brief history • Treatment • Conclusions • Prescription drugs: more in urban and rural areas rather than large cities • Possible reasons: • - Heroin not as available as prescription drugs • - Prescription drugs more socially acceptable • - Easier to attain and cheaper Cicero, Surratt, & Inciardi, (2007)

8. Gender Differences • 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)

9. Opiate vs. Opioid • Background • Opioid vs opiate • Brief history • Treatment • Conclusions • Opiate • Natural origin, made from opium (Papaver somniferum) • Examples • - Morphine • - Codeine • - Thebaine Renner & Levounis (2011)

10. Opiate vs. Opioid • 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)

11. Abuse Potential • 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)

12. History • 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)

13. History of Opium • 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)

14. History • 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)

15. History • 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)

16. History • Background • Opioid vs opiate • Brief history • Treatment • Conclusions • Opiate: Thebaine • Not used for therapeutic purposes • Used for semisynthetic opioids • Examples • - Percocet • - Percodan • - OxyContin (oxycodone) McKim & Hancock (2013)

17. History • 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)

18. Background • Opioid vs. opiate • Brief history • Treatment • Conclusions Treatment Considerations • Mu receptor • Full agonist • Antagonists • Partial agonist Renner & Levounis (2011)

19. Background • Opioid vs. opiate • Brief history • Treatment • Conclusions Treatment Considerations • Full Agonist • Prescription opioids • Morphine • Heroin • Methadone Renner & Levounis (2011)

20. 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)

21. Background • Opioid vs. opiate • Brief history • Treatment • Conclusions Treatment Considerations • Partial Agonist • Buprenorphine • - Longer half-life • - Can relieve opioid and opiate withdrawal symptoms Renner & Levounis (2011)

22. Background • Opioid vs. opiate • Brief history • Treatment • Conclusions Buprenorphine • Originally developed in the 1970s • Developed because • - Opioid addiction is costly to the government • - Methadone treatment had many associatedlimitations Renner & Levounis (2011)

23. Background • Opioid vs. opiate • Brief history • Treatment • Conclusions Buprenorphine • Administration Routes • Subutex form • Administered orally • Buprenorphine alone • Suboxone form • Administered orally • Mix of buprenorphine/naloxone • (3) Implants • (4) Injections Renner & Levounis (2011)

24. Background • Opioid vs. opiate • Brief history • Treatment • Conclusions Buprenorphine Implants • 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)

25. Background • Opioid vs. opiate • Brief history • Treatment • Conclusions Buprenorphine Injections • 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)

26. Background • Opioid vs. opiate • Brief history • Treatment • Conclusions Buprenorphine -naloxone • Adding naloxone discourages parenteral use BUTpreserves the therapeutic effect on opiate addiction when used sublingually as intended (Harris, Jones, Welm, Upton, Lin & Mendelson, 2000)

27. Background • Opioid vs. opiate • Brief history • Treatment • Conclusions Gender Differences • 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)

28. Background • Opioid vs. opiate • Brief history • Treatment • Conclusions Conclusions • Advantages of Buprenorphine • Partial agonist • Improved overall safety margin • Long-lasting effect • Reduces severity of withdrawal Renner & Levounis (2011)

29. Background • Opioid vs. opiate • Brief history • Treatment • Conclusions Conclusions • Disadavantages of Buprenorphine • Concern of abuse • Need to be aware of potential for abuse Cicero, Surratt, Inciardi, & Munoz (2007)

30. Background • Opioid vs. opiate • Brief history • Treatment • Conclusions “Holy Grail of Opioid Research” • 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)

31. Acknowledgments • Conference organizers • Behavioral Science Department • Drs. David Yells and Richard Nance • Dr. Claudia Lieberwirth

32. 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-of-treatment opioid-addicted individuals. The American Journal of Drug and Alcohol Abuse, 35, 38-42. doi: 10.1080/00952990802342915

33. 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

34. Questions?