Download Pharmacologic Treatments of Alcohol Dependence

Alcoholism Treatment Matching:
Methodological and Clinical Issues
Dennis M. Donovan, Ph.D.
Alcohol & Drug Abuse Institute
and
Department of Psychiatry & Behavioral
Sciences
University of Washington
CONJ 556:
Addiction: Mechanisms, Prevention, Treatment
The World's Largest 6-Pack:
“Honestly, Officer, I only had one can….”
Spectrum of Intervention Response
Thresholds for Action
No
Problems
Mild
Problems
Moderate
Problems
Severe
Problems
Treatment
Brief Intervention
Primary Prevention
The CURE for
addiction as
a brain disease
http://www.recoveryjonescartoons.com/cartoons.htm
Selection of Level of Intensity of Intervention
No Intervention Needed
Brief Intervention
Self-Help Groups
Outpatient Treatment
Severity of
Dependence
Intensive Day or
Night Treatment
Residential Treatment
Miller, 1989
Institute of Medicine Report: Broadening the
Base of Treatment for Alcohol Problems (1990)
• It may no longer be appropriate to ask if
treatment works, which is the best available
treatment, or which treatment is more
effective than another.
• The question needs to be reframed:
“Which kinds of individuals, with what kinds of
alcohol problems, are likely to respond to
what kind of treatments by achieving what
kinds of goals when delivered by which kinds
of practitioners?”
What Is Treatment Matching?
“Deliberate and consistent attempt to
select a specific candidate for a specific
method of intervention in order to
achieve specific goals.”
Glaser & Skinner, 1982
The “Science” of Treatment Selection and Matching
“I utilize the best from Freud, the best from Jung, and
the best from my Uncle Marty, a very smart fellow.”
Key Conceptual and Methodological
Issues in Patient-Treatment Matching
Conceptual issues:
• Selecting effective matching variables
• Specifying the end result that matching is to enhance
• Determining the stage(s) in the treatment process at
which matching decisions are to be made
Methodological issues deal with the type of patienttreatment match or interaction effect and include:
• Nonlinear interaction effects
• Higher-order interaction effects
• Multilevel interaction effects
Finney & Moos, 1986
Conditions Enhancing Probability of Identifying Interaction
Effects Testing the Treatment Matching Hypothesis
• Large clinical sample, allowing subject
heterogeneity for meaningful subtypes
• Controlled trial with random assignment
to treatment conditions
• Use of reliable and valid instruments to
assess prognostic characteristics
• Well-defined treatments that are clearly
differentiable
• Use of a multidimensional assessment
approach
1992
• Inclusion of psychological variables
(including degree of alcohol dependence)
and demographic characteristics
• Use of data analytic strategies that are
appropriate for the detection of complex
interactions while also controlling for
prognostic indicators
Methods of Treatment Matching
• Client preference/self-selection
• Client attribute by type of treatment
(e.g., Project MATCH)
• Identified problem by services provided
(e.g., McLellan / ASI)
• Severity of substance abuse problems /
consequences by treatment intensity or
setting (e.g., ASAM Criteria)
Degree of Empirical Evaluation Relative to
Implementation of Matching Approaches
High
Empirical Evaluation
ClientTreatment
ProblemServices
Low
SeveritySetting
Client
Preference
Low
High
Implementation
Methods of Treatment Matching:
Client Preference/Self-Selection
Role of Client Choice in the Therapy Process
• A common clinical process following
assessment is that the client is advised
of the “appropriate” form of therapy.
• This is seen as undermining the client’s
sense of responsibility with regard to the
therapeutic process and may lead to
dissatisfaction, reduced compliance and
dropout.
Van Audenhove & Vertommen, 2000
Role of Client Choice in the Therapy Process
Treatment goals and approaches that
have been chosen by the client, either
independently or through negotiation
with the clinician, are likely to capitalize
on the client’s motivation and to
increase compliance.
Miller, 1989
“try to make me go to rehab,
i won't go, no, no, no…!”
Does Self-Selection of Treatments Lead to
Better Outcomes than Random Assignment?
• Receiving treatment of preference had no
measurable impact on treatment outcome,
either for drinking behavior or general
functioning.
• Receiving treatment of preference had no
measurable impact on treatment process,
utilizing client-rated (satisfaction and
effectiveness), clinician rated (rapport and
engagement) and objective (number of
sessions attended) measures.
Adamson, Sellman, & Dore, 2005
Self-Directed Care
• A system that is “intended to
allow informed consumers to
assess their own needs . . .
determine how and by whom
these needs should be met, and
monitor the quality of services
they receive” (Dougherty, 2003).
SAMHSA, 2004
• A system “in which funds that
would ordinarily be paid to
service provider agencies are
transferred to consumers, using
various formulas to account for
direct, administrative, and other
costs.” (Cook et al., 2004).
Patient-Centered Care
“Patient-centered care” is care that is
“respectful of and responsive to
individual patient preferences, needs,
and values and ensures that patient
values guide all clinical decisions.”
• Patient access to and receipt of
information that permits informed health
care decisions
• Supporting the client through
disagreements about treatment decisions
• Asking the patient’s goals for recovery
• Factoring these into shared decision
making for the recovery process
Source: Institute of Medicine (2006), Improving the Quality
of Health Care for Mental and Substance-Use Conditions.
• Assessing and supplementing
education/information
Methods of Treatment Matching:
Client Attribute by Type of Treatment
(e.g., Project MATCH)
Matching Alcoholism Treatment to Client Heterogeneity
Purpose of Project MATCH
To determine if various types of
alcoholics respond differentially to
different treatment approaches
Why a Multi-Site Matching Trial?
• There is considerable heterogeneity
among alcoholics
• No single treatment helps all alcoholics
• Promising results in small-scale
matching studies
• Matching is a dominant question on the
research agenda
Clinical Research Units
Project MATCH
Milwaukee
Seattle
*
Buffalo
*
VAMC
*
Albuquerque
Houston
VAMC
Providence
* ***
WHaven
VAMC
* Farmington
*
Charleston
VAMC
Two Parallel Study Arms
To test the generalizability of matching in
different client populations and
treatment settings


Outpatient
Aftercare
Project MATCH Therapy Manuals
To evaluate matching clients to distinct, manual-driven,
theoretically-based treatments that are widely applicable
to a range of settings and providers
Research Design: Outpatient Study
Recruitment from
Community at 5 sites
Random
Assignment
Motivational
Enhancement
Therapy
Cognitive
Behavioral
Training
Twelve
Step
Facilitation
Assessment and Follow-up Protocol
• Baseline Pre-Treatment
• End of Treatment (Month 3)
• Post-Treatment Follow-up: Mos 6, 9, 12, 15
• All contacts were in person except month 12
• Self reports corroborated by blood/urine
samples and collateral reports
Client Attributes Examined in
Project MATCH
•
•
•
•
•
•
•
•
•
Gender
Alcohol involvement
Cognitive impairment
Meaning seeking
(spirituality)
Motivation
Sociopathy
Social network support
for drinking
Alcohol dependence
Level of anger
• Interpersonal
dependency
• Prior AA involvement
• Self-efficacy
• Social functioning
• Antisocial personality
disorder
• Type and severity of
psychiatric disorder
• Religiosity
• Alcoholism type
• Readiness to change.
Outcome Variables
Primary Measures
• Percent of Days Abstinent (frequency)
• Drinks per Drinking Day (intensity)
Secondary Measures (Partial list)
• Other measures of drinking
• Negative consequences of drinking
• Other substance use
• Social functioning
• Psychological functioning
Compliance in Project MATCH:
Treatment Attendance
Percent of Prescribed Sessions
100
90
80
70
60
50
40
30
20
10
0
CB
MET
TS
Outpatient
Aftercare
The Crushing Weight of the Data
Mean Percent Days Abstinent as a
Function of Time (Outpatient)
100
90
80
70
60
50
40
30
20
10
0
CBT
MET
TSF
-2 -1
0
4
Project MATCH Research Group, 1997
5
6
7
8
9 10 11 12 13 14 15
Proportion of Patients Maintaining Total
Abstinence as a Function of Time (Outpatient)
Proportion of Clients
1.2
1
0.8
CBT
MET
TSF
0.6
0.4
0.2
0
1
3
7
14 30 60 90 120 150 180 240 300 360
Time in Days
Mean Number of Drinks
Mean Drinks per Drinking Day as a
Function of Time (Outpatient)
14
12
10
CBT
MET
TSF
8
6
4
2
0
-2 -1
0
4
5
6
7
8
9 10 11 12 13 14 15
Time in Months
Project MATCH Research Group, 1997
Proportion of Outpatients Avoiding a
Heavy Drinking Day as a Function of Time
Proportion of Clients
1.2
1
0.8
CBT
MET
TSF
0.6
0.4
0.2
0
1
3
7
14 30 60 90 120 150 180 240 300 360
Time in Days
Project MATCH Research Group, 1997
Only 4 of 21Possible Treatment - Attribute
Matches Found in Project MATCH
Alcohol Dependence: In the aftercare group, individuals
with high levels of alcohol dependence benefited more
from TSF than from CBT, whereas the reverse was true
for patients low in dependence.
Psychopathology: In the outpatient group, those without
psychopathology were found to benefit more from TSF
than from CBT.
Anger: Also in the outpatient arm of the trial, patients high
in anger had more successful outcomes with the MET
than with the other two approaches.
Social Network Support for Abstinence: Patients whose
social networks offered less support for abstinence had
better outcomes in TSF than in MET.
Project MATCH Findings
• Treatment attendance was high across all three
treatments
• Excellent overall outcomes, with substantial
reductions in frequency and intensity of drinking
following treatment
• Few differences among treatments
• Outcomes similar for MET vs. CBT+TSF
• Observed main effects generally favored TSF
• Outcomes are not substantially improved by
client-treatment matching.
“In sum, Project MATCH’s findings
challenged the notion that patient-treatment
matching is a prerequisite for optimal
alcoholism treatment. Other than the four
relationships, the findings did not show that
matches between patient characteristics
and treatments produced substantially
better outcomes.”
NIAAA's 10th Report to Congress
Was Project MATCH Right After All?
Witkiewitz: J Abnorm Psychol, 116(2). 2007.378–394
Original Project MATCH Hypothesis:
Individuals lower in baseline selfefficacy would have better outcomes if
they were randomly assigned to CBT
rather than to MET.
Original Project MATCH Finding:
No interaction effect obtained.
Witkiewitz, et al., Finding:
Provided support for the original selfefficacy matching hypotheses. Baseline
self-efficacy was related to different
outcomes depending on whether
individual was randomly assigned to
CBT or to MET, and this relationship
was moderated by levels of drinking
frequency.
Interaction between self-efficacy and treatment
assignment on percentage of drinking days for
infrequent drinking class (top) and frequent drinking
class (bottom)
Witkiewitz: J Abnorm Psychol, 116(2). 2007.378–394
Subsequent Therapy Component by
Client Attribute Interactions
• A focus on emotional material in therapy was associated
with more frequent alcohol consumption among patients
high in depressive symptoms
• Therapist use of confrontation was associated with more
frequent alcohol consumption among patients at medium
and high levels of trait anger while it was associated with
less frequent alcohol consumption among patients low in
anger
• Confrontation was associated with more frequent alcohol
consumption among patients high in interpersonal
reactance (extent to which an individual generally resists
being influenced by others)
• Therapy structure was associated with more frequent
alcohol consumption among patients at medium or high
levels of reactance
Karno & Longabaugh, Addiction, 102, 587–596, 2007
Effects of Match between Patient Depressive
Symptoms and Therapy Emotion Focus
PDA
100
90
80
70
60
50
40
30
20
10
0
Matched
Unmatched Mismatched
Karno & Longabaugh, Addiction, 102, 587–596, 2007
% Recovered
Matched
Unmatched Mismatched
Do Client Attribute / Treatment Matches
Matter?
• Mismatches between patient attributes and
treatment appear to have serious
consequences, and this effect is magnified
with multiple mismatches.
• Matches, on the other hand, while beneficial,
may not be necessary to achieve good
outcomes
Karno & Longabaugh, Addiction, 102, 587–596, 2007
Still left with variable response…..
• Even when treatment delivery is standardized
and high adherence to manual is achieved,
some patients do well and others do not.
• Very hard to predict who will do well in a
particular treatment
• Nonresponse is often blamed on the patient,
but that is likely not the whole story.
Another Possible Approach?
Adaptive Treatment
In Adaptive Treatment Protocols…
• One of the conceptual issues identified by Finney &
Moos (1986): Determining the stage(s) in the
treatment process at which matching decisions are to
be made
• Treatment is tailored or modified on the basis of
measures of response (e.g., symptoms, status, or
functioning) obtained at regular intervals during
treatment
• Goal is to deliver the least burdensome treatment
that is effective, to promote better compliance over
time
• Rules for changing treatment are clearly
operationalized and described…..
“If……..Then”
Decision Rules
If (tailoring variable)
then (decision option)
Example:
If client does not
complete web-based
CBT assignments for 2
weeks
Provide telephone
Motivational Interviewing
session
Operationalizing Clinical Decisions
• Reduces inappropriate variance in
treatment delivery
• Provides framework for improving
outcomes
• Permits systematic research
An Example of an Adaptive Strategy for Aftercare for
Patients Recently Treated for Substance Use Disorder
(SUD) and Depression
Goal: minimize
relapse for all treated
within constraints of
health care system
SUD AND depression in
remission
Telephone contact
with BS Staff
1 per 7 days
Evaluate at 6 weeks
on risk factors for
BOTH SUD and Depression
Risk Low
for BOTH
Risk Moderate for
ONE OR MORE
Decrease telephone
contact to once per 14
Days with BS level staff
Increase
telephone contact once
Per 5 days with therapist
Baseline
Sequential,
Multiple
Assignment,
Randomized
Trial
(SMART)
Randomization
Treatment
Assessment
Assessment
NonResponder
Control
Responder
NonResponder
Responder
Final
Outcome
Final
Outcome
Randomization
Randomization
Switch
Treatment
No
Change
Reduce
Treatment
Burden
Final
Outcome
Final
Outcome
Final
Outcome
No
Change
Final
Outcome
Combined Pharmacological and Behavioral
Interventions for Alcohol Dependence
Ways in Which Psychopharmacology Is Used to
Treat Alcohol or Other Drug Dependencies
Purpose
Relapse
Prevention
Treatment Goal
Examples
• Make drinking alcohol
aversive
Disulfiram
(Antabuse)
• Reduce alcohol craving
Naltrexone (ReVia,
Vivitrol)
Acamprosate
(Campral)
Three Medications Approved by the FDA for Use in
the Treatment of Alcohol Dependence
Rationale for Project COMBINE
• Recent advances have occurred in the
development of pharmacological and behavioral
treatments for alcohol dependence
• The hypothesis that pharmacological and
behavioral treatments may enhance each other
and yield optimal improvement rates requires
investigation
• COMBINE will evaluate the efficacy of
naltrexone, acamprosate, and psychotherapy
individually and in combination
Effect of Alcoholism Typology on Response to Naltrexone in
the COMBINE Study
FIGURE 1.
Percent Heavy Drinking Days by Typology and Medication Condition
Babor’s Type A Alcoholism
• Later age of alcoholism onset
80
• Weaker family history (i.e.,
Percent
70
Heavy
Drinking
60
Days
Lines: Top to Bottom at 4 months
Type A Placebo
Type B Naltrexone
Type B Placebo
Type A Naltrexone
50
40
30
• Less severe dependence
• Fewer symptoms of cooccurring psychiatric disorders
20
10
0
Baseline
• Fewer first-degree relatives
who are alcoholics)
Month 1
Month 2
Month 3
Month 4
Among those receiving medication management without
CBI, Type A alcoholics had better drinking outcomes with
naltrexone than placebo, whereas medication condition
did not influence outcomes significantly in the Type Bs.
For those who received CBI, there were no significant
effects of A/B typology.
Bogenschutz, Tonigan, Pettinati, under review
• Less psychosocial
impairment (i.e., negative
familial, social, legal, or
occupational consequences of
drinking).
Methods of Treatment Matching:
Identified Problem by Services Provided
(e.g., McLellan / ASI)
Drug Abuse Treatment Core Components
and Comprehensive Services
Financial
Services
Housing &
Transportation
Child Care
Core
Treatment
Behavioral
Therapy and
Counseling
Clinical and
Case
Management
Medical
Services
Mental
Health
Intake
Processing/
Assessment
Vocational
Treatment
Plan
Pharmacotherapy
Substance Use
Monitoring
Self-Help/Peer
Support Groups
Continuing Care
Family
Services
AIDS/HIV
Services
Legal
Services
Educational
An investigation that randomized 94
patients to problem–service matching
versus standard services found that
those who received three or more
service sessions matched to mental
health, family or employment problems
had better treatment completion and
post-treatment outcomes.
McLellan et al., 1997
Change in “Wrap-Around” Services
1980s (TOPS) vs. 1990s (DATOS)
1980s
77
1990s
60
50
15
20
5
LTR
ODF
OMT
Percent of Sample Receiving 2 or More Services
Etheridge, Craddock, Dunteman, & Hubbard, 1995
Change in “Wrap-Around” Services
1980s (TOPS) vs. 1990s (DATOS)
1980s
1990s
68
43
26
23
21
10
Medical
Services
Psychol
Services
10
Family
Services
10
Educational
Services
Percent of Outpatient Psychosocial Treatment Sample
Etheridge, Hubbard, Anderson, Craddock, & Flynn, 1997
Effects of Comprehensive Matching of
Service Needs on Drug Use Outcomes
• Examined five areas of need: medical, mental, vocational,
family, and housing
• Most participants indicated needing at least one service
(an average of 3.22 services needed per person)
• Only about 1/3 of service needs were met/matched
– (1.11 met, 2.22 unmet)
• Overall, matching of needs with services was associated
with significant reductions in drug use
• Of the five areas, only matching on mental health failed to
be associated with improved drug use outcomes
• The effects of matching are greater for clients with high
needs (having needs in 4-5 areas) than those with low
needs
Friedmann, et al., 2004
Computer-Assisted System for Patient
Assessment and Referral: CASPAR
Compared to clients of counselors conducting
standard assessments, those of counselors using
CASPAR
• Had treatment plans that were better matched to
their needs
• Received significantly more and better-matched
services
• Were less likely to leave treatment against
medical advice
• Were more likely to complete the full course of
treatment than patients of counselors in the SA
group.
Methods of Treatment Matching:
Severity of Substance Abuse Problems
and Consequences
by Treatment Intensity or Setting
(e.g., ASAM Patient Placement Criteria)
ASAM Criteria Describe Levels of Treatment
Differentiated by Three Characteristics
• Degree of direct medical management
provided
• Degree of structure, safety, and security
provided
• Degree of treatment intensity provided
ASAM PLACEMENT CRITERIA
LEVELS OF
OF CARE
CRITERIA
I. OUTPT
II. INTENSIVE
OUTPT
III. MED
MON INPT
IV. MED
MGD INPT
Withdrawal
no risk
minimal
Medical
Complications
no risk
manageable
some risk
medical
monitoring
required
Psych/Behav
Complications
no risk
severe risk
24-hr acute
med. care
required
24-hr psych.
& addiction
Tx required
Readiness
For Change
cooperative
Relapse
Potential
maintains
abstinence
mild severity
cooperative
but requires
structure
more symptoms,
needs close
monitoring
supportive
less support,
w/ structure
can cope
Recovery
Environment
moderate
high resist.,
needs 24-hr
motivating
unable to
control use in
outpt care
danger to
recovery,
logistical
incapacity
for outpt
Finding from Research on ASAM
Patient Placement Criteria
• Individuals who receive a less intensive level of
care than recommended have poorer outcomes
than those who receive the recommended level
• Receiving a more intensive level of care than
recommended did not improve outcomes over
those for appropriately matched level of care
• There is substantial disagreement between
clinicians’ recommended level of care and that
recommended by a computer algorithm (which
recommended more intensive levels than did
counselors)
Practical Barriers to Implementing
Matching Procedures
• Lack of true alternative treatments either within a
given program or across programs in a
community
• Need to specify the treatments long a number of
theoretically or therapeutically relevant
dimensions
• Need to specify the individual client
characteristics or problems at which the
treatment is targeted
• Practical impact of the increased workload in
order to provide the necessary assessments and
treatments
Donovan & Mattson, 1994
Practical Barriers to Implementing
Matching Procedures
• Need to account for influence of therapist
characteristics either within or across
treatment modalities
• Potential requirement of “staged” matching
across different levels of motivation or
readiness to change and phases of treatment
and recovery
• Need to determine the best methods of and
criteria for matching clients to treatment
Donovan & Mattson, 1994
Suggestions for Conceptual Changes
in Allocation Research
• Extend the scope of relevant factors in change
processes
– Clarify the relevance of social support for maintaining
or reducing problematic substance use
– Study patient–therapist interactions
– Study site effects
• Clarify the relevance of patient decision making for
treatment allocation
– Analyze the relevance of motivation/readiness for
change
– Clarify the role of patients’ treatment choices
• Search for mediator and moderator effects
Bühringer, 2006
Suggestions for Conceptual Changes
in Allocation Research
• Consider treatment ‘macro-level’ allocation
needs in practice (setting, duration, intensity)
– Determine the need for in-patient/residential
interventions
– Improve the knowledge on duration versus
intensity of interventions
– Determine the choice of relevant problem areas
for treatment
Bühringer, 2006
Suggestions for Methodological Changes
in Allocation Research
• Maximize patient heterogeneity, increasing
external validity
• Maximize intervention heterogeneity
– have a larger variation in the time and intensity of
treatment
– intensify the exposure of specific intervention
techniques, in order to achieve larger betweentreatment effects
• Implement more adequate research designs
Bühringer, 2006