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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
Thousands of New Users
2500
Pain Relievers
2000
1500
Tranquilizers
1000
Stimulants
500
Sedatives
0
1965
1970
1975
1980
1985
1990
1995
2000
Source: National Survey on Drug Abuse, 2001
Narcotic Painkiller Admissions, by Age:
1997 and 2002
No. of Admissions (000s)
3
1997
2002
2.5
2
1.5
1
0.5
0
10
15
20
25
30
35
40
45
50
55
60
Age of Admission
Source: The DASIS Report, Treatment Admissions Involving
Narcotic Painkillers: 2002 Update
Current Use of Prescription Drugs for Nonmedical
Purposes in 1999
Millions of Americans
3
2.7
2.5
2
1.4
1.5
1
1
0.5
0
Stimulants
Sedatives and
Pain Relievers
Tranquilizers
Source: Office of Applied Studies, Substance Abuse and Mental Health Services
Administration, National Household Survey on Drug Abuse, 1999
Absolute Dollars in Millions, 2002 Adjusted
Promotional Spending for Three Opioid Analgesics
in First 6 Years of Sales
30
25
MS Contin: 1984-1989
OxyContin: 1996-2001
Duragesic: 1991-1996
20
15
10
5
0
Year 1
Year 2
Year 3
Year 4
Year 5
Year 6
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
Past year users
Past year abuse
or dependence
Past year
dependence
Number
Percent
(pop)
Percent Percent Percent
(pop)
(users)
(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
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 Abuse
DSM-IV Dependence
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
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
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 DSMIII-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
Percentage of Patients with a Current Substance Use Disorder
other than Opioid Substance Use Disorder
40
Abuse
Dependence
30
20
10
0
Alcohol
Sedative-Hypnotic
Cannabis
Stimulant
Percentage of Patients
Percentage of Patients with a Past Substance Use Disorder
other than Opioid Substance Use Disorder
40
30
20
10
0
Alcohol
Sedative-Hypnotic
Cannabis
Stimulant
Source: U. Busto et al, Can J Clin Pharmacol Vol 5 No 1 (1998) 23-28
Combinations of Current Psychoactive
Substance Use Disorders
Opioid and SedativeHypnotics (19%)
Opioid only (34%)
Opioid and Alcohol (9%)
Opioid and one other (2%)
Opioid and at least 2 others (36%):
Alcohol, Sedative-Hypnotics,
Cannabis, Cocaine, Polydrug
Hallucinogens, Stimulants
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
3-5 Criteria
6 Criteria
All 9 Criteria
7 Criteria
8 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
Source: U. Busto et al, Can J Clin Pharmacol Vol 5 No 1 (1998) 23-28
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.
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’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
DSM-IV Criteria in Dependent Group
100
80
% 60
40
20
0
Tolerance
Withdrawal
Using More
Unable to
Stop
Problems
Time
Replacing
Activities
Most Common Psychological and Physical
Problems Associated with Codeine Use
25
20
% 15
10
5
0
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-Dependent
Mean 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 Program Retention
Cumulative 2-Year Retention in the CAMH MMT Program
for 3 Chronological Patient Cohorts
1.2
Cohort 1 (n=63)
Cohort 2 (n=95)
1
Cohort 3 (n=82)
0.8
0.6
0.4
0.2
0
4
8
12
16
20
24
Treatment Duration (months)
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
Dr. E. M. Sellers
Ms. K. Knight
Mr. A. MacDonald
• Funding: CAMH, OMHF
Ms. J. Blake
Dr. D. Gourlay
Ms. G. Somer
Ms. H. Kameh