1. Prescription Opioid Abuse and Dependence Usoa E. Busto, Pharm.D. Beth Sproule, Pharm. D. Bruna Brands, Ph.D. Centre for Addiction and Mental Health October 18, 2004

2. Prescription Opioids Prescription opioids are widely used for pain management and bring important improvements in quality of life However most opioid medications have a potential to be abused and cause dependence e.g. morphine, hydromorphone, oxycodone, hydrocodone, and codeine

3. Prescription Opioids The challenge is to balance the need to make psychotropic medications readily available for therapeutic use while minimizing the risk of their abuse.

4. Annual Numbers of New Nonmedical Users of Psychotherapeutics: 1965-2000 0 500 1000 1500 2000 2500 19651970197519801985199019952000 Thousands of New Users Pain Relievers Tranquilizers Stimulants Sedatives Source: National Survey on Drug Abuse, 2001

5. Narcotic Painkiller Admissions, by Age: 1997 and 2002 0 0.5 1 1.5 2 2.5 3 1015202530354045505560 Age of Admission No. of Admissions (000s) 1997 2002 Source: The DASIS Report, Treatment Admissions Involving Narcotic Painkillers: 2002 Update

6. Current Use of Prescription Drugs for Nonmedical Purposes in 1999 1 1.4 2.7 0 0.5 1 1.5 2 2.5 3 StimulantsSedatives and Tranquilizers Pain Relievers Millions of Americans Source: Office of Applied Studies, Substance Abuse and Mental Health Services Administration, National Household Survey on Drug Abuse, 1999

7. Promotional Spending for Three Opioid Analgesics in First 6 Years of Sales 0 5 10 15 20 25 30 Year 1Year 2Year 3Year 4Year 5Year 6 Absolute Dollars in Millions, 2002 Adjusted MS Contin: 1984-1989 OxyContin: 1996-2001 Duragesic: 1991-1996 Source: United States GAO-04-110 Report to Congressional Requesters, Oxytocin Abuse and Diversion and Efforts to Address the Problem

8. Estimated numbers (in thousands) and percentages of persons reporting past year use of, past year abuse of, or dependence on opioids and tranquilizers NumberPercent (pop) Percent (users) Percent (pop) Percent (users) Opioids83533.70.411.80.37.9 Tranquilizers36731.60.16.60.13.2 Past year usersPast year abuse or dependence Past year dependence Source: J. Zacny et al, Drug and Alcohol Dependence 69, (2003) 215-232

9. Terminology “Substance Abuse” used broadly Any useSubstance use disorders DSM-IV Dependence Any 3 of: tolerance withdrawal uses more or longer than intended unable to cut down use consumes a great deal of time important social/work activities given up continued use despite psychological or physical problems known to be caused by substance DSM-IV Abuse Any 1 of: recurrent use causing failure to fulfill major role obligations at work/home/school recurrent use when physically hazardous recurrent substance-related legal problems continued use despite persistent social/interpersonal problems due to substance use

10. Prescription Opioid Abuse/Dependence we do not know the prevalence of prescription opioid use disorders nor the characteristics or life circumstances of the individuals that develop these disorders we know very little about how regular opioid use evolves into problematic use and substance use disorders

11. Study 1. Interviews with Oral Opioid Dependent Inpatients Objectives: To determine the characteristics, patterns of drug use, treatment and outcome of patients severely dependent on oral opioids Subjects: 58 patients (60% male, mean age 35.4  9.5 years) admitted to the inpatient Medical Unit of the Addiction Research Foundation Methods: Data collected prospectively by structured interview using the psychoactive substance use module of the Structured Clinical Interview for DSM- III-R (SCID). Busto UE, Sproule BA, Knight K, Romach MK, Sellers EM. Severe dependence on oral opiates. The Canadian Journal of Clinical Pharmacology 1998;5(1):23-28.

12. Demographic characteristics of severely opioid-dependent patients (N=58) number% SexMale Female 35 23 60 40 Admission age (yrs) 20-29 30-39 40-69 Mean age (  SD) 15 31 11 35.4  9.5 28 53 19 EducationPublic school or lower Some secondary school Secondary school completed Post secondary school incomplete Post secondary school completed 4 18 19 10 6 7 32 33 17 10 Source: U. Busto et al, Can J Clin Pharmacol Vol 5 No 1 (1998) 23-28

13. Percentage of Patients with aCurrent Substance Use Disorder other than Opioid Substance Use Disorder 0 10 20 30 40 AlcoholSedative-HypnoticCannabisStimulant Percentage of Patients Abuse Dependence Percentage of Patients with aPast Substance Use Disorder other than Opioid Substance Use Disorder 0 10 20 30 40 AlcoholSedative-HypnoticCannabisStimulant Percentage of Patients Source: U. Busto et al, Can J Clin Pharmacol Vol 5 No 1 (1998) 23-28

14. Combinations of Current Psychoactive Substance Use Disorders Opioid only (34%) Opioid and one other (2%) Opioid and Alcohol (9%) Opioid and Sedative- Hypnotics (19%) Alcohol, Sedative-Hypnotics, Cannabis, Cocaine, Polydrug Hallucinogens, Stimulants Opioid and at least 2 others (36%): Source: U. Busto et al, Can J Clin Pharmacol Vol 5 No 1 (1998) 23-28

15. Proportion of Opioid-Dependent Patients Meeting DSM-III-R Criteria for Current Opioid Dependence All 9 Criteria 7 Criteria 6 Criteria 3-5 Criteria Withdrawal Symptoms, Marked Tolerance, Inability to Stop, Persistent Use, Use in Spite of Problems, Withdrawal Relief, Hazardous Use, Much Time Spent Getting Substance, Use Interferes with Activities 8 Criteria Source: U. Busto et al, Can J Clin Pharmacol Vol 5 No 1 (1998) 23-28

16. Study 1 cont’d Results: mean daily dose of codeine: 554  343 mg (range 120mg to 1500mg) mean daily oxycodone dose (in codeine equivalents): 1265  1377 mg, range 333 to 6670 mg, p<0.01) 36% also met criteria for abuse or dependence on at least 2 other substances mean duration of opioid use at the current dose: 7 years majority obtained opioids by going to different physicians (39%), although 26% got their opioids primarily from one physician 26% purchased oral opioids off the street Busto UE, Sproule BA, Knight K, Romach MK, Sellers EM. Severe dependence on oral opiates. The Canadian Journal of Clinical Pharmacology 1998;5(1):23-28.

17. Study 2 - Survey of Regular Users of Codeine Objectives: to determine the characteristics of a broader population of regular opioid users Subjects: n=339 individuals who were using codeine at least 3 days per week for the past 6 months (excluding cancer pain patients); 49% males, mean age 43 ± 12 years Methods: anonymous 27 page questionnaire assessment of codeine dependence and abuse in the past year was made on the basis of written short answers to open-ended questions two trained investigators evaluated the responses to determine whether the criteria were clearly met, clearly not met, or whether it could not be determined on the basis of the information provided

18. Study 2 cont’d Results: currently using acetaminophen with codeine products (30mg 37%, 8mg 23%) mean daily dose of 115mg (range 8-1200mg) at least 5-6 days per week (70%) used an average of 12 ± 9 years 37% (n=124) met DSM-IV criteria for codeine dependence 30% identified themselves with problematic codeine use most obtained codeine from one physician (66%) most (81%) reported chronic pain (55% headaches) Sproule BA, Busto UE, Somer G, Romach MK, Sellers EM. Characteristics of dependent and non-dependent regular users of codeine. Journal of Clinical Psychopharmacology 1999;19(4):367-372

19. DSM-IV Criteria in Dependent Group %

20. Most Common Psychological and Physical Problems Associated with Codeine Use %

21. Study 2 cont’d dependent subjects currently found codeine less effective for treating pain only 42% of the dependent subjects with chronic pain had tried non-opioid medication for their pain dependent subjects were more likely to use codeine for pleasurable effects, to relax, or to prevent withdrawal symptoms subjects in the dependent group also obtained their codeine from friends (32%), from family (11%), off the street (19%), and through prescriptions from more than one doctor (11%) Sproule BA, Busto UE, Somer G, Romach MK, Sellers EM. Characteristics of dependent and non-dependent regular users of codeine. Journal of Clinical Psychopharmacology 1999;19(4):367-372

22. Dependent vs Non-Dependent Subjects DependentNon-Dependent Mean Daily Dose176 mg74mg Alcohol Problems57%26% Cannabis Problems23%5% Sought help for mental health problem 76%55% Psychiatric hospitalization22%8%

23. Study 2 cont’d Conclusions: chronic codeine use is associated with dependence, as well as substantial comorbid pain and psychiatric problems Sproule BA, Busto UE, Somer G, Romach MK, Sellers EM. Characteristics of dependent and non-dependent regular users of codeine. Journal of Clinical Psychopharmacology 1999;19(4):367-372

24. Study 3. Retrospective Study of Prescription Opioid Use in Methadone Maintenance Patients steep increase in the number of patients dependent on prescription opioids admitted to our methadone maintenance treatment program following an expansion in service in the latter half of the 1990s in Ontario detailed retrospective chart review of patients admitted to methadone maintenance treatment after program expansion was conducted n=178, mean age=34.5±0.7 years, 65% male at admission most patients (82%) had been using prescription opioids (± heroin)

25. Drug use history for three chronological patient cohorts at the time of admission to MMT Cohort 1Cohort 2Cohort 3p value % Currently injecting drugs 81.078.946.30.0001 Hepatitis C seroprevalence: % positive 90.478.555.80.0001 Source: B. Brands et al, Drug and Alcohol Dependence 66, (2002) 11-20

26. Cumulative 2-Year Retention in the CAMH MMT Program for 3 Chronological Patient Cohorts 0.2 0.4 0.6 0.8 1 1.2 04812162024 Treatment Duration (months) Cumulative Program Retention Cohort 1 (n=63) Cohort 2 (n=95) Cohort 3 (n=82) Source: B. Brands et al, Drug and Alcohol Dependence 66, (2002) 11-20

27. Overall Summary Points Prescription opioid abuse/dependence has not been well studied. There are indicators that this may be an increasing problem. Severe dependence on oral opioids is possible, and is likely to be associated with polysubstance abuse and treatment relapse. Regular codeine use is associated with substantial dependence, although the exact prevalence is not known. Psychiatric comorbidity is very common. Pain was not optimally treated in these patients. Prescription opioid dependent has increased among patients admitted to our methadone maintenance treatment program, again with indications of significant psychiatric comorbidity in this population.

28. Prescription Opioid Abuse and Dependence Acknowledgements Dr. M. RomachMs. J. Blake Dr. E. M. SellersDr. D. Gourlay Ms. K. KnightMs. G. Somer Mr. A. MacDonaldMs. H. Kameh Funding: CAMH, OMHF