Raymond J. Carroll Texas A&M University carroll [email protected] Postdoctoral Training Program:
Kathleen M Carroll PhD Yale University School of Medicine Dual Addictions Kathleen M Carroll PhD...
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Dual Addictions
Kathleen M Carroll PhDKathleen M Carroll PhDYale University School of Yale University School of
MedicineMedicine
Overview
• Definitions and terms
• Epidemiology: Rates and risks
• Onset: Gateways and destinations
• Treatments: Everything we don’t know
Terms
Comorbidity: Co-occurrence of two conditions or disorders
Dual diagnosis: Co-occurrence of alcohol/drug use disorder and another psychiatric disorder (heterotypic comorbidity)
Homotypic comorbidity: Co-occurrence of disorders within a diagnostic grouping (e.g., substance use disorders)
Major US epidemiologic surveysEpidemiologic Catchment Area Study (ECA)
1980-1984
N=20291 adults 18+
DSM-III
(DIS)
Regier et al., 1990
National Comorbidity Survey (NCS)
1990-1992
N=8098
15-54
DSM-III-R
(CIDI)
Kessler et al. 1994
NCS-R 2001-2002
N=9282 adults
DSM-IV
(CIDI)
Kessler et al.
2005
**NESARC 2001-2002
N=43093
adults
DSM-IV Grant et al., 2004
National Epidemiologic Survey on Alcohol and Related Conditions
(NESARC)• Previous surveys in US, Canada, Australia
confirm probabilities of alcohol use disorder rise with drug use disorder visa versa
• Only NESARC diagnosis specific (multiple types of drugs rather than ‘lumping’)
• Includes data on help seeking• Focus on 12-month (current), rather than lifetime
disorders• Oversampling of African Americans and Hispanics
DSM-IV Substance Dependence
Maladaptive use leading to clinically significant impairment or distress, shown by 3+ of the following in the same 12-month period:
1. Use of the substance more or longer than intended2. Persistent desire or unsuccessful efforts to cut down or
stop3. A great deal of time spent on use of the substance or
getting over its effects4. Important activities given up or reduced because of use5. Continued use despite knowledge of a serious physical or
psychological problem6. Tolerance7. Withdrawal, or use to avoid withdrawal
DSM-IV Substance Abuse
Not dependent, and maladaptive use leading to clinically significant impairment or distress, shown by 1 + of the following:
1. Continued use despite social/interpersonal problems
2. Hazardous use (e.g., driving when impaired by alcohol)
3. Frequent use leading to failure to function in major roles
4. Legal problems
NESARC: 12-month prevalence rates
Disorder 12-month prevalence
Population estimate (thous)
Any alcohol use disorder 8.5 17580
Any alcohol use only 7.4 15285
Any drug use disorder 2.0 4159
Any alcohol use + drug use disorder 1.1 2295
Any drug use disorder only 0.9 1864
Any drug abuse 1.4 2858
Any drug dependence 0.6 1301
Stinson et al, (2005) DAD
12-month prevalence: Drug use disorders
Disorder % abuse % dependence Pop est (thou)
Cannabis 1.13 0.32 3016
Opioid .24 .11 737
Cocaine .13 .13 557
Amphetamine .09 .07 342
Sedative .09 .07 333
Hallucinogen .12 .02 291
Tranquilizer .08 .05 260
Solvent/ inhalant
.02 - 49
Stinson et al, (2005) DAD
Demographics:
Users of alcohol + drugs more likely to be:
• Male (74%)
• Younger (18-29) (65%)
• Never married (63%)
• Similar to drug-only with respect to education, ethnicity, income
Disorder Prevalence (%)
Any drug dependence 67.7
Any drug abuse 49.5
Cocaine 79.5
Hallucinogen 79.2
Amphetamine 62.8
Solvent /inhalant abuse 59.9
Opioids 57.5
Cannabis 57.6
Tranquilizers 57.5
Sedatives 39.8
Rates of alcohol use disorders among those with specific drug use disorders: NESARC
% alcohol use disorder, given drug use
% drug use disorder, given alcohol use
Any drug dependence 67.7 5.01
Any drug use 49.5 8.04
Cocaine 79.5 2.51
Hallucinogen 79.2 1.31
Amphetamine 62.8 1.22
Solvent /inhalant 59.9 0.17
Opioids 57.5 2.41
Cannabis 57.6 9.89
Tranquilizers 57.5 0.85
Sedatives 39.8 0.75
Alcohol use among those with specific drug use disorders and visa-versa
Comorbidity: NESARC
Disorder No alcohol or drug
Alcohol only
Drug only
Alcohol + any drug
Any personality disorder
13.2 25.3 44.0 50.8
Any mood disorder, past yr
8.1 16.4 27.5 35.3
Any anxiety disorder, past yr
10.4 15.6 24.0 26.5
Stinson et al, (2005) DAD
12-month prevalence treatment seeking by disorder: NESARC
0
5
10
15
20
25
Alcohol only Drug only Alcohol and anydrug
Stinson et al, (2005) DAD
12-month prevalence treatment seeking by disorder: NESARC
0102030405060708090
100
Alcohol only Drug only Alcohol and anydrug
Factors associated with multiple substance use
• Retention of use through gateway progression
• Pharmacologic effects of combinations, including modulation, treatment of withdrawal and uncomfortable effects
• Genetic evidence of common mechanisms, vulnerability in some families
• Availability, market trends
Gateway pattern of drug initiation: Kandel et al
Cigarettes
Alcohol
Cannabis
Other illicit
NCS-R: Only 5.2%Violate this pattern
Risk of developing disorder, given use
0
5
10
15
20
25
30
35
Tobacco Alcohol Heroin Cocaine Cannabis Tranqul.
Anthony et al. 1994, Comparative epidemiology, NCS
NESARC: Hazard rates for alcohol and drug use disorders
Hasin et al., 2007Arch Gen Psychiatry
Compton et al. 2007Arch Gen Psychiatry
Drug-alcohol comorbidity associated with:
• Earlier onset
• Higher severity
• Higher psychiatric comorbidity
• Higher rates of treatment seeking
• Higher rates of dropout once in treatment
• Less socioeconomic support
• Poorer treatment outcome
Limited research on treatment of homotypic comorbidity
Users of multiple substances usually excluded from treatment research:
• Difficulty in meeting needs of heterogeneous populations in single trial
• Complexity of assessment (time frame, availability of biologic indicators, time)
• Complexity of targeting multiple substances simultaneously (licit, illicit)Safety and compliance concerns, especially in pharmacologic trials
• Pharmacologic specificity
Rounsaville et al, 2003
Available pharmacotherapies for substance use disorders
Alcohol Opioids Cocaine Marijuana
Detoxification X x - -
Maintenance X
Antagonist X
Aversive, reduce craving
X
Treat co-existing psychiatric disorders
X X X X
Emerging pharmacologic strategies for homotypic comorbidity
Type Medication Reference
Opioid alcohol Naltrexone Volpicelli et al (1992)
O’Malley et al (1992)
Alcohol cocaine Disulfiram Carroll et al. (2004)
Original rationale for disulfiram as treatment for cocaine users
• Clinical observation of high levels of concurrent alcohol-cocaine use (60-70% of patients)
• Rationale: Reducing alcohol use may reduce concurrent cocaine use
1. Better ability to utilize coping skills (Marlatt et al)
2. Alcohol powerful conditioned cue (Higgins et al)3. Cocaethylene (Jatlow, McCance)
Open outpatient study, cocaine-alcohol users: % attaining 3+
weeks abstinence
0
10
20
30
40
50
60
70
TSF CBT CM/DISULF TSF/DISULF CBT/DISULF
Carroll et al., 1998
Double blind trial of disulfiram for cocaine dependence in methadone
maintenance N=67
0
10
20
30
40
50
60
70
Disulfiram Placebo
% cocaine neg urines% days coc. abst
Petrakis et al 2000
Randomized outpatient clinical trial: Disulfiram, CBT, and IPT, N=121
Frequency of cocaine use by treatment week
0
0.5
1
1.5
2
2.5
3
3.5
0 1 2 3 4 5 6 7 8 9 10 11 12
Treatment week
Day
s of
use
CBT/Disulfiram
IPT/Disulfiram
CBT/Placebo
IPT/Placebo
Carroll et al., 2004
z p
Time -7.15 .00
Disulfiram x time -2.10 .04
CBT x time -2.33 .03
Disulfiram x CBT x time
-1.97 .05
Cocaine outcomes for those who did NOT Cocaine outcomes for those who did NOT meet criteria for alcohol abuse or meet criteria for alcohol abuse or dependence (n=58) dependence (n=58)
Behavioral therapy studies of alcohol-drug users
Behavioral therapies tend to be effective across types of substance use
Alcohol Opioids Cocaine Marijuana Mixed
Motivational interviewing
X (X) (X) X (X)
Contingency management
X X X X X*
Cognitive behavioral therapies
X X X X X
Behavioral couples, family therapies
X X X X X
Clinical Trials Network:17 Current Nodes, >200
CTPs
Clinical Trials Network: MET Trials Participant Characteristics
• Mean age 35• 29% female (<MI)• 42% Caucasian (<MI)• 12 years of education• 28% mandated or legal referral
• Primary substance use problem:• Alcohol: 29 % (<MI)• Marijuana: 16%• Cocaine: 23% (>MI)• Methamphetamine: 4% (<MI)• Opioids: 9%• Benzodiazepenes: 1%
Ball et al., 2007
CTN MET/MI studies: Design
Individual presents for treatment at clinicScreened for studyInformed consent
Baseline assessment Randomization
Standard individual treatment @ CTP
3 sessions
3 sessionsWith MET
Posttreatment assessment28 days after randomization
84-day (3 month) follow-up
CTN: MET longitudinal outcomes
0.00
0.50
1.00
1.50
2.00
2.50
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16
CAU MET
Days of Use - all sites
Ball et al.., 2007
CTN MET/MI studies: Outcomes for alcohol subgroups
Engagement Substance use outcomes
Alcohol use only subgroup
MI (1 session)
Carroll et al. (2007)
+ - +
MET (3 sessions)
Ball et al. (2007)
- (+) +
MET-Spanish
(3 sessions)
Under review
- - +
‘CBT 4 CBT’Computer Based Therapy/CBT
• 6 modules, ~1 hour each, high flexibility• Highly user friendly, no text to read, linear navigation• Video examples of characters struggling real life
situations• Multimedia presentation of skills• Repeat movie with character using skills to change ‘ending’• Interactive exercises, quizzes • Multiple examples of ‘homework’
Computer-based training in CBT: CBT4CBT
“All comers”: few restriction on participation, only require some drug use in past 30 days
• 43% female• 45% African American, 12% Hispanic • 23% employed• 37% on probation/parole• 59% primary cocaine problem, 18% alcohol,
16% opioids, 7% marijuana• 79% users of more than one drug or alcohol
Carroll et al., in press, Am J Psychiatry
Primary outcomes, 8 weeksCBT+TAU versus TAU
34
53
0
10
20
30
40
50
60
70
80
% drug positive urines
CBT4CBT + TAUTAU
Carroll et al., in press, Am J Psychiatry
Treatment of Dual Addictions:General strategies
• Target, treat most severe disorder and any requiring detoxification first
• Utilize pharmacotherapies when available
• Attend to psychiatric and medical comorbidity
• Frequent monitoring, chronic care model
• Sequential targeting may be important for some treatments (eg. contingency management)
“I wonder why we’re not getting any new converts.”