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Long-Term Course of Opioid Addiction Yih-Ing Hser, Ph.D. UCLA Integrated Substance Abuse Programs Addiction Seminar (Psychiatry 434) Supported by the National Institute on Drug Abuse (P30 DA016383)

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Page 1: Long-Term Course of Opioid Addiction Long-Term Course of Opioid Addiction Yih-Ing Hser, Ph.D. UCLA Integrated Substance Abuse Programs Addiction Seminar

Long-Term Course of Opioid Addiction

Yih-Ing Hser, Ph.D.

UCLA Integrated Substance Abuse Programs

Addiction Seminar (Psychiatry 434)

Supported by the National Institute on Drug Abuse (P30 DA016383)

Page 2: Long-Term Course of Opioid Addiction Long-Term Course of Opioid Addiction Yih-Ing Hser, Ph.D. UCLA Integrated Substance Abuse Programs Addiction Seminar

Overview Background

4 CALDAR

4 This topic

Overview of morality and opioid abstinence in long-term follow-up studies

The 33-year follow-up study

The START follow-up study

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Page 3: Long-Term Course of Opioid Addiction Long-Term Course of Opioid Addiction Yih-Ing Hser, Ph.D. UCLA Integrated Substance Abuse Programs Addiction Seminar

Center for Advancing Longitudinal Drug Abuse Research (CALDAR)

Increase knowledge of patterns of drug addiction & their interplay with treatment and other service systems

Enhance scientific collaboration through integration analysis, training, consultation, dissemination

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Page 4: Long-Term Course of Opioid Addiction Long-Term Course of Opioid Addiction Yih-Ing Hser, Ph.D. UCLA Integrated Substance Abuse Programs Addiction Seminar

Examples of CALDAR’sLong-term Follow-up Studies

1. The 33-year follow-up study of heroin addicts

2. A 12-year follow-up of a cocaine-dependent sample

3. A 5-year follow-up of participants in the Amity treatment program at a correction facility

4. Follow-up studies of methamphetamine patients

5. An 10-year follow-up of mothers and their children

6. START follow-up study

(Starting Treatment with Agonist Replacement Therapy—Randomization to Suboxone vs. Methadone)

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Page 5: Long-Term Course of Opioid Addiction Long-Term Course of Opioid Addiction Yih-Ing Hser, Ph.D. UCLA Integrated Substance Abuse Programs Addiction Seminar

Longitudinal Research Design

In contrast to cross-sectional research design—data are collected on one or more variables for a single time periodLongitudinal research design—data are collected on one or more variables for two or more time periods

► Longitudinal research design allows measurement of change, and possibly explanation of change

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Page 6: Long-Term Course of Opioid Addiction Long-Term Course of Opioid Addiction Yih-Ing Hser, Ph.D. UCLA Integrated Substance Abuse Programs Addiction Seminar

Goals of Longitudinal Analyses

Assess changes over time: ► How does it change over time?► What is the time trend?► How does the time trend differ by group?► Group differences at end of study (group

differences at end of study) minus (group differences at baseline)

Investigate factors related to the different patterns of changes

► Time trends as functions of covariates

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Page 7: Long-Term Course of Opioid Addiction Long-Term Course of Opioid Addiction Yih-Ing Hser, Ph.D. UCLA Integrated Substance Abuse Programs Addiction Seminar

Persistence of drug use: Drug addiction is a chronic condition

High relapse rates over long periods of time

Non-compliance, require long-term care management

Frequent encounters with social and health service systems

Longitudinal Drug Abuse Research

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Page 8: Long-Term Course of Opioid Addiction Long-Term Course of Opioid Addiction Yih-Ing Hser, Ph.D. UCLA Integrated Substance Abuse Programs Addiction Seminar

Life Course Perspective on Drug use

1. Life course theory recognizes the importance of time, timing, and temporal processes in the study of human behavior and experience over the life span, characterized by trajectories, transitions, and turning points

2. Persistence of drug use resembles chronic diseases: high relapse rates, non-compliance, require long-term care/management

3. Critical life events often lead to or explain changes

4. Social capital, situated choice are additional key concepts

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Page 9: Long-Term Course of Opioid Addiction Long-Term Course of Opioid Addiction Yih-Ing Hser, Ph.D. UCLA Integrated Substance Abuse Programs Addiction Seminar

Longitudinal Approach to Study Drug Use over Time

Protective Factore.g. family support

Protective Factor(occurrence of positive life events)

e.g. got married, got employed

Risk Factorse.g. crime involvement

Estimated trajectory of Drug use

Age

Life-course Drug Use Career

Age

Trajectories of drug use are heterogeneous among individuals and can be classified as several distinctive

trajectory groups

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Page 10: Long-Term Course of Opioid Addiction Long-Term Course of Opioid Addiction Yih-Ing Hser, Ph.D. UCLA Integrated Substance Abuse Programs Addiction Seminar

Global Burden of Disease

Approximately 16.5 millions people worldwide are users of heroin or opium (UN World Drug Report 2013)

In the US, approximately 467,000 individuals with heroin use disorder; 2,056,000 with prescription pain relievers in 2012 (NSDUH)

Opioid dependence is the biggest contributor to overdose deaths

Opioid dependence is the biggest contributor to global burden of disease attributable to illicit drug use and dependence

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Page 11: Long-Term Course of Opioid Addiction Long-Term Course of Opioid Addiction Yih-Ing Hser, Ph.D. UCLA Integrated Substance Abuse Programs Addiction Seminar

A 33-year Follow-up of Heroin-Dependent Sample

A cohort of 581 male heroin addicts admitted to the California Civil Addict Program (CAP) in 1962-64 has been followed-up and interviewed over more than 30 years

The CAP was the only major publicly-funded drug treatment program available in California in the 1960s

The CAP provided a combination of inpatient and outpatient drug treatment to narcotics-dependent criminal offenders committed under court order

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Page 12: Long-Term Course of Opioid Addiction Long-Term Course of Opioid Addiction Yih-Ing Hser, Ph.D. UCLA Integrated Substance Abuse Programs Addiction Seminar

Life Course of Heroin Addiction

Death: 14%Negative urine on heroin: 29%

Incarcerated: 18%

28%25%12%

49%23%6%

Childhood/Adolescence

Young Adulthood Adulthood Middle-aged

Late-middle-aged & Older

CAPAdmission

Mean age = 25

Larger society/environment Drug itself Individual: social relationship (family, school, church),

education/employment, institutional interaction (CJS, treatment), health/mental health

Influencing Factors

Onset of HeroinMean age = 18

Follow-up at 1974/75

Mean age = 40

Follow-up at 1985/86

Mean age = 50

Follow-up at 1996/97

Mean age = 60

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Page 13: Long-Term Course of Opioid Addiction Long-Term Course of Opioid Addiction Yih-Ing Hser, Ph.D. UCLA Integrated Substance Abuse Programs Addiction Seminar

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Hypothetical Drug Use Trajectories

0

5

10

15

20

25

30

1 24 36 48 60 84 96 108 120 132 180

Months

Days

of use

Person 1 Person 2 Person 3

IncarceratedDrug txEmploymentMental health txCriminally active

Page 14: Long-Term Course of Opioid Addiction Long-Term Course of Opioid Addiction Yih-Ing Hser, Ph.D. UCLA Integrated Substance Abuse Programs Addiction Seminar

The Natural History of Narcotics Addiction Among CAP Sample

(N=581)

0

20

40

60

80

100

56 58 60 62 64 66 68 70 72 74 76 78 80 82 84 86 88 90 92 94 96

Per

cen

t of

Sam

ple

Daily Narcotic Use

Methadone Maintenance

Abstinent

Occasional Narcotic Use

Incarcerated

Dead

Unknown

Years 1956 through 1996 14

Page 15: Long-Term Course of Opioid Addiction Long-Term Course of Opioid Addiction Yih-Ing Hser, Ph.D. UCLA Integrated Substance Abuse Programs Addiction Seminar

Identify Groups with Distinctive Heroin Use Trajectories

Growth Mixture Modeling

First half of the observation (16 years) since heroin initiation

Two-part model (skewness)

Linear and quadratic terms

Three Distinctive Groups

Standard statistical criteria: BIC,entropy

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Page 16: Long-Term Course of Opioid Addiction Long-Term Course of Opioid Addiction Yih-Ing Hser, Ph.D. UCLA Integrated Substance Abuse Programs Addiction Seminar

Mean Number of Days Per MonthUsing Heroin, 33 Year Follow-up

0

5

10

15

20

25

30

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16

Years since first heroin use

Days

use

d

Decelerate Stably High Quitter

9%

32%

59%

16

Page 17: Long-Term Course of Opioid Addiction Long-Term Course of Opioid Addiction Yih-Ing Hser, Ph.D. UCLA Integrated Substance Abuse Programs Addiction Seminar

Differences in Trajectory Groups: Demographics

59

29

3834

66

50

7612

0

20

40

60

80

Late Decelerated Stably High Use Early Quitter

%

White Hispanic African American

17**p < .01Note: (no difference in education or age)

Page 18: Long-Term Course of Opioid Addiction Long-Term Course of Opioid Addiction Yih-Ing Hser, Ph.D. UCLA Integrated Substance Abuse Programs Addiction Seminar

Differences in Trajectory Groups: Mortality

50.3

38.1

25.0

0

20

40

60

80

Late Decelerated Stably High Use Early Quitter

Per

cen

t

18**p < .01

Page 19: Long-Term Course of Opioid Addiction Long-Term Course of Opioid Addiction Yih-Ing Hser, Ph.D. UCLA Integrated Substance Abuse Programs Addiction Seminar

Consistent with other studies showing:

Some users did stop using Many continued to use at high

levels, over a long period of time At any given time, 40-60%

“relapsed”

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Page 20: Long-Term Course of Opioid Addiction Long-Term Course of Opioid Addiction Yih-Ing Hser, Ph.D. UCLA Integrated Substance Abuse Programs Addiction Seminar

What New? Distinctive patterns of drug use

trajectory Individual’s baseline not

necessarily determines future Important to identify why the

different patterns of trajectory Escalating Decreasing High vs. low vs. no use

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Page 21: Long-Term Course of Opioid Addiction Long-Term Course of Opioid Addiction Yih-Ing Hser, Ph.D. UCLA Integrated Substance Abuse Programs Addiction Seminar

What Have we Learned? Cyclical patterns of abstinence and

use of different levels, protracting over a long time

Long-term observation is necessary to explicate addiction patterns and

trajectories. Otherwise, we may miss the critical points or differences as

well as opportunities for intervening If addiction is a chronic disease and

cumulative treatment effect exists, then long-term care makes sense for these individuals 21 21

Page 22: Long-Term Course of Opioid Addiction Long-Term Course of Opioid Addiction Yih-Ing Hser, Ph.D. UCLA Integrated Substance Abuse Programs Addiction Seminar

Is stable long-term recovery possible?

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Page 23: Long-Term Course of Opioid Addiction Long-Term Course of Opioid Addiction Yih-Ing Hser, Ph.D. UCLA Integrated Substance Abuse Programs Addiction Seminar

Rates of Abstinence by Years Abstinent Prior to Last Interview

(N = 242)

15% 17%

75% 72%

0

20

40

60

80

0(n = 85)

1-5(n = 66)

6-15(n = 36)

15+(n = 34)

Years Abstinent Prior to 1985/86

Per

cen

t A

bst

inen

t (1

985/

86 t

o p

rese

nt)

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Page 24: Long-Term Course of Opioid Addiction Long-Term Course of Opioid Addiction Yih-Ing Hser, Ph.D. UCLA Integrated Substance Abuse Programs Addiction Seminar

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More than 5 Years of Abstinence:Predicting lower depression

1.61.5

1.3 1.3 1.31.2

0

0.4

0.8

1.2

1.6

2

Me

an

Sc

ore

Depression * Anxiety

No abstinence (N=121) 1-<5 Years (n=31) 5+ Years (n=69)

* p < .05SCL58 Scale (1- 4) at the 33-year follow-up: higher scores indicate greater symptom severity.

Page 25: Long-Term Course of Opioid Addiction Long-Term Course of Opioid Addiction Yih-Ing Hser, Ph.D. UCLA Integrated Substance Abuse Programs Addiction Seminar

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More than 5 Years of Abstinence:Predicting better emotional well-being

74.078.0 83.0

53.0

65.0

59.0

0

20

40

60

80

100

Me

an

Sc

ore

Emotion* Health

No abstinence (N=121) 1-<5 Years (n=31) 5+ Years (n=69)

p < .05 SF36 Scale (0-100) at the 33-year Follow-up: higher scores indicate better a status

Page 26: Long-Term Course of Opioid Addiction Long-Term Course of Opioid Addiction Yih-Ing Hser, Ph.D. UCLA Integrated Substance Abuse Programs Addiction Seminar

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19.121.5

22.8

8.39.7

12.4

0

10

20

30

Me

an

Sc

ore

Self-esteem ** Life satisfication **

No abstinence (N=121) 1-<5 Years (n=31) 5+ Years (n=69)

* p<.05; **p < .01Self-Esteem (0-30) and Life Satisfaction (0-18) Scales at the 33-year : Higher scores indicate a better status

More than 5 Years of Abstinence: Higher self-esteem and life satisfaction

Page 27: Long-Term Course of Opioid Addiction Long-Term Course of Opioid Addiction Yih-Ing Hser, Ph.D. UCLA Integrated Substance Abuse Programs Addiction Seminar

27

64

45

9

35 32

14 18 16

6

5661

43

78

65

48

0

20

40

60

80

100

per

cen

t o

f su

bje

cts

Heroin ** Coca/Meth*

Other illictdrugs *

Alcohol Tobacco **

No abstinence (N=121) 1-<5 Years (n=31) 5+ Years (n=69)* p<.05; **p < .01

Alcohol, Tobacco and Illicit Drug Use

at the 33-year Follow-up

Page 28: Long-Term Course of Opioid Addiction Long-Term Course of Opioid Addiction Yih-Ing Hser, Ph.D. UCLA Integrated Substance Abuse Programs Addiction Seminar

28

18

39

58

0

20

40

60

80

100

pe

rce

nt

of

su

bje

cts

Employed **

No abstinence (N=121) 1-<5 Years (n=31) 5+ Years (n=69)

* p<.05; **p < .01

Employment at the 33-year Follow-up

Page 29: Long-Term Course of Opioid Addiction Long-Term Course of Opioid Addiction Yih-Ing Hser, Ph.D. UCLA Integrated Substance Abuse Programs Addiction Seminar

Summary of Findings Five years appear to be a good benchmark

4 Less future use4 Less CJS involvement4 Better emotional and social functioning

Timing may be critical4 Health is not much better4 Alcohol and tobacco still problematic

Need to 4 Understand the underlying mechanisms 4 Promote recovery in early stages of

addiction

Page 30: Long-Term Course of Opioid Addiction Long-Term Course of Opioid Addiction Yih-Ing Hser, Ph.D. UCLA Integrated Substance Abuse Programs Addiction Seminar

CTN START: Background1267 opioid dependent users

Randomly assigned to Suboxone vs. Methadone

Recruitment over the period of 2006 to 2009

Mortality status (date of death) determined by 3/2012

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START: Starting Treatment with Agonist Replacement TherapySuboxone (Buprenorphine+naloxone) vs. Methadone

Page 31: Long-Term Course of Opioid Addiction Long-Term Course of Opioid Addiction Yih-Ing Hser, Ph.D. UCLA Integrated Substance Abuse Programs Addiction Seminar

Medications for Opioid Addiction

Methadone: agonist Morphine Tincture of opium Naltrexone:antagonist Depo-naltrexone Buprenorphine: partial agonist

Subutex, Suboxone, Probuphine Clonidine: non-opioid Lofexidine

OOH O

N

OHCH3 CH2

CH2 CH N

CH3CH3

CH3

O

Page 32: Long-Term Course of Opioid Addiction Long-Term Course of Opioid Addiction Yih-Ing Hser, Ph.D. UCLA Integrated Substance Abuse Programs Addiction Seminar

START: Study Sites

8 sites (across 5 states) California

Bi-Valley Medical Clinic Inc., Sacramento (n=117/84; 201) BAART, Turk St. Clinic, San Francisco (n=109/78; 187) Matrix Institute, Los Angeles (n=78/50; 128)

Oregon CODA-Research, Portland (n=136/89; 225)

Washington Evergreen Treatment Services, Seattle (n=79/55; 134)

Connecticut CT Counseling Centers, Waterbury (n=71/52; 123) Hartford Dispensary, Hartford (n=101/71; 172)

Pennsylvania NET Steps, Philadelphia (n=48/49; 97)

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Page 33: Long-Term Course of Opioid Addiction Long-Term Course of Opioid Addiction Yih-Ing Hser, Ph.D. UCLA Integrated Substance Abuse Programs Addiction Seminar

START: Treatment &

Randomization 24 weeks (active phase), ending 36 weeks

739 to Suboxone vs. 528 to Methadone

2006 71 vs. 72 1:1

2007 207 vs. 197 1:1

2008 254 vs. 139 2:1

2009 192 vs. 99 2:1

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Page 34: Long-Term Course of Opioid Addiction Long-Term Course of Opioid Addiction Yih-Ing Hser, Ph.D. UCLA Integrated Substance Abuse Programs Addiction Seminar

Data CollectionBaseline (randomization)

Demographics, substance use/urine, physical and psychiatric history, quality of health

START treatment Suboxone vs. methadone, days in treatment, dose

3 waves of follow-up starting late 2011

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Page 35: Long-Term Course of Opioid Addiction Long-Term Course of Opioid Addiction Yih-Ing Hser, Ph.D. UCLA Integrated Substance Abuse Programs Addiction Seminar

Research Questions

Mortality Treatment retention Long-term use

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Page 36: Long-Term Course of Opioid Addiction Long-Term Course of Opioid Addiction Yih-Ing Hser, Ph.D. UCLA Integrated Substance Abuse Programs Addiction Seminar

Description of Sample at Baseline: Demographics

Mean age 37Female 32%Ethnicity

White 72%Black 8%Hispanics 12%

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Page 37: Long-Term Course of Opioid Addiction Long-Term Course of Opioid Addiction Yih-Ing Hser, Ph.D. UCLA Integrated Substance Abuse Programs Addiction Seminar

Description of Sample at Baseline: Opioid and Other

DrugsUrine

Positive (%) Use

Disorder (%)

Amphetamine 9 11Cannabis 24 20

Cocaine 37 33

Opiates 97 100

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Page 38: Long-Term Course of Opioid Addiction Long-Term Course of Opioid Addiction Yih-Ing Hser, Ph.D. UCLA Integrated Substance Abuse Programs Addiction Seminar

Description of Sample at Baseline: smoking and alcohol

use

Current smoker 89%Alcohol use disorder 23%

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Page 39: Long-Term Course of Opioid Addiction Long-Term Course of Opioid Addiction Yih-Ing Hser, Ph.D. UCLA Integrated Substance Abuse Programs Addiction Seminar

Description of Sample at Baseline: psychiatric history

Schizophrenia 2.5%Major depressive disorder 28%Bipolar 12%Anxiety or panic disorder 30%

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Page 40: Long-Term Course of Opioid Addiction Long-Term Course of Opioid Addiction Yih-Ing Hser, Ph.D. UCLA Integrated Substance Abuse Programs Addiction Seminar

Description of Sample at Baseline: Quality of health1

Percentile 2

Physical 49 (9)Mental health 39 (13)

1. SF-362. Relative to the U.S. population with similar age & gender

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Page 41: Long-Term Course of Opioid Addiction Long-Term Course of Opioid Addiction Yih-Ing Hser, Ph.D. UCLA Integrated Substance Abuse Programs Addiction Seminar

Baseline differences between the two treatment conditions

No differences inAge, gender, ethnicity, injection, sites, alcohol, amphetamine, cannabis, sedativePhysical and mental health quality

Exceptions: cocaine & smoking (higher in the methadone group)

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Page 42: Long-Term Course of Opioid Addiction Long-Term Course of Opioid Addiction Yih-Ing Hser, Ph.D. UCLA Integrated Substance Abuse Programs Addiction Seminar

START Treatment

Treatment condition Suboxone58%

Methadone42%

Days in treatment1 (within 168 days)

99 (70) 138 (54)

Treatment completion2 46% 74%Average dose, mg 14 (8) 68 (35)

1. The difference between the two treatment groups was significant at p < .01

2. The difference between the two treatment groups was significant at p < .01

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Page 43: Long-Term Course of Opioid Addiction Long-Term Course of Opioid Addiction Yih-Ing Hser, Ph.D. UCLA Integrated Substance Abuse Programs Addiction Seminar

Mortality

Mortality status (date of death) determined by 3/2012 Web archives: date of death

CDC National Death Index: date and ICD-10 causes of death

CDC has a 2-year lag time in their data

Death certificates from local corner’s office

Page 44: Long-Term Course of Opioid Addiction Long-Term Course of Opioid Addiction Yih-Ing Hser, Ph.D. UCLA Integrated Substance Abuse Programs Addiction Seminar

0

0.2

0.4

0.6

0.8

1

0 20 40 60 80 100

120

140

160

168

Surv

ival

Days in treatment during 24 weeks

Buprenorphine (n=738) Methadone (n=529)

Figure 1. Survival Curves for Buprenorphine Versus Methadone

1

Page 45: Long-Term Course of Opioid Addiction Long-Term Course of Opioid Addiction Yih-Ing Hser, Ph.D. UCLA Integrated Substance Abuse Programs Addiction Seminar

11.8%

5.8%8.7%

23.3% 35.6%

17.1%

Page 46: Long-Term Course of Opioid Addiction Long-Term Course of Opioid Addiction Yih-Ing Hser, Ph.D. UCLA Integrated Substance Abuse Programs Addiction Seminar

0102030405060708090

100

0 1 2 3 4 5 6 7 8 9

10 11 12 13 14 15 16 17 18 19 20 21 22 23 24

Week in Treatment

Suboxone Dose (n=739)

Suboxone with Positive Urine (n=739)

Methadone Dose (n=528)

Methadone with Positive Urine (n=528)

Figure 3. Average Weekly Dose and Positive Opiate over Weeks in Treatment (n=1,267)

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Page 47: Long-Term Course of Opioid Addiction Long-Term Course of Opioid Addiction Yih-Ing Hser, Ph.D. UCLA Integrated Substance Abuse Programs Addiction Seminar

To improve retention, clinicians need to

1. use higher medication doses, particularly for BUP,

2. address continued use of opiates and other drugs, and

3. identify additional factors/strategies influencing BUP retention, particularly during the first 30 days of treatment.

Page 48: Long-Term Course of Opioid Addiction Long-Term Course of Opioid Addiction Yih-Ing Hser, Ph.D. UCLA Integrated Substance Abuse Programs Addiction Seminar

48

The Future? Changing profiles of opioid addiction Evidence-based intervention, practice, &

principles Long-term care or management Service structure

4 Integration within treatment systems4 Integration across systems4 Affordable Care Act

Technology

Page 49: Long-Term Course of Opioid Addiction Long-Term Course of Opioid Addiction Yih-Ing Hser, Ph.D. UCLA Integrated Substance Abuse Programs Addiction Seminar

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Longitudinal Studies and Analyses Two or more observations of the response variable taken

at different times are made on the same individuals

Can be used to assess on-going/recurring behaviors & events

Adjust for correlated observations over time, and/or

Allow examination of both within- and between-subjects hypotheses, i. e. can separate

differences within individuals (e.g. aging/drug career progression), from

differences among people (cohort effects)

Allow complexity, depending on models chosen: covariates (both time-variant and time-invariant), missing data, clustering of observations, latent constructs, temporal structuring

More powerful for some hypotheses than cross-sectional designs

Page 50: Long-Term Course of Opioid Addiction Long-Term Course of Opioid Addiction Yih-Ing Hser, Ph.D. UCLA Integrated Substance Abuse Programs Addiction Seminar

Learn more about longitudinal research

findings and modeling techniques??

See CALDAR website (www.caldar.org) for new findings, development, and workshops

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