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

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

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.

Annual Numbers of New Nonmedical Users of

Psychotherapeutics: 1965-2000

0

500

1000

1500

2000

2500

1965 1970 1975 1980 1985 1990 1995 2000

Th

ou

san

ds

of

New

Use

rs

Pain Relievers

Tranquilizers

Stimulants

Sedatives

Source: National Survey on Drug Abuse, 2001

Narcotic Painkiller Admissions, by Age:

1997 and 2002

0

0.5

1

1.5

2

2.5

3

10 15 20 25 30 35 40 45 50 55 60

Age of Admission

No

. o

f A

dm

issi

on

s (0

00s) 1997

2002

Source: The DASIS Report, Treatment Admissions Involving

Narcotic Painkillers: 2002 Update

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

Stimulants Sedatives andTranquilizers

Pain Relievers

Mil

lio

ns

of

Am

eric

ans

Source: Office of Applied Studies, Substance Abuse and Mental Health Services

Administration, National Household Survey on Drug Abuse, 1999

Promotional Spending for Three Opioid Analgesics

in First 6 Years of Sales

0

5

10

15

20

25

30

Year 1 Year 2 Year 3 Year 4 Year 5 Year 6

Ab

solu

te D

olla

rs in

Mill

ion

s, 2

002

Adj

uste

d MS Contin: 1984-1989OxyContin: 1996-2001Duragesic: 1991-1996

Source: United States GAO-04-110 Report to Congressional Requesters, Oxytocin

Abuse and Diversion and Efforts to Address the Problem

Estimated numbers (in thousands) and percentages of persons reporting past year use of, past year abuse

of, or dependence on opioids and tranquilizers

Number Percent (pop)

Percent (pop)

Percent (users)

Percent (pop)

Percent (users)

Opioids 8353 3.7 0.4 11.8 0.3 7.9

Tranquilizers 3673 1.6 0.1 6.6 0.1 3.2

Past year users Past year abuse

or dependence

Past year dependence

Source: J. Zacny et al, Drug and Alcohol Dependence 69, (2003) 215-232

Terminology

“Substance Abuse” used broadly

Any use Substance use disorders

DSM-IV DependenceAny 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 AbuseAny 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

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

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.

Demographic characteristics of severely opioid-dependent patients (N=58)

number %

Sex Male

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

Education Public 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

Percentage of Patients with a Current Substance Use Disorder

other than Opioid Substance Use Disorder

0

10

20

30

40

Alcohol Sedative-Hypnotic Cannabis Stimulant

Per

cen

tag

e o

f P

atie

nts

Abuse

Dependence

Percentage of Patients with a Past Substance Use Disorder

other than Opioid Substance Use Disorder

0

10

20

30

40

Alcohol Sedative-Hypnotic Cannabis Stimulant

Per

cen

tag

e o

f P

atie

nts

Source: U. Busto et al, Can J Clin Pharmacol Vol 5 No 1 (1998) 23-28

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

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

Study 1 cont’dResults:

• 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.

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

Study 2 cont’dResults:

• 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

DSM-IV Criteria in Dependent Group

0

20

40

60

80

100

Tolerance Withdrawal Using More Unable toStop

Problems Time ReplacingActivities

%

Most Common Psychological and Physical Problems Associated with Codeine Use

0

5

10

15

20

25

Depression Anxiety GI Disturbances Constipation Headaches

%

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

Dependent vs Non-Dependent Subjects

Dependent Non-DependentMean Daily Dose 176 mg 74mg

Alcohol Problems 57% 26%

Cannabis Problems 23% 5%

Sought help for mental health problem

76% 55%

Psychiatric hospitalization 22% 8%

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

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)

Drug use history for three chronological patient cohorts at the time of admission to MMT

Cohort 1 Cohort 2 Cohort 3 p value

% Currently injecting drugs

81.0 78.9 46.3 0.0001

Hepatitis C seroprevalence: % positive

90.4 78.5 55.8 0.0001

Source: B. Brands et al, Drug and Alcohol Dependence 66, (2002) 11-20

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

0 4 8 12 16 20 24

Treatment Duration (months)

Cu

mu

lati

ve P

rog

ram

Re

ten

tio

n 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

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.

Prescription Opioid Abuse and Dependence

• Acknowledgements

• Dr. M. Romach Ms. J. Blake

• Dr. E. M. Sellers Dr. D. Gourlay

• Ms. K. Knight Ms. G. Somer

• Mr. A. MacDonald Ms. H. Kameh

• Funding: CAMH, OMHF