measuring outcome in the treatment of cocaine dependence paul crits-christoph, ph.d. mary beth...
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Measuring Outcome in the Treatment of Cocaine Dependence
Paul Crits-Christoph, Ph.D.Mary Beth Connolly Gibbons, Ph.D.
Robert Gallop, Ph.D.Jaclyn S. Sadicario, B.A.
George Woody, M.D.
Department of PsychiatryUniversity of Pennsylvania
Primary Goal of NIDA Cocaine Collaborative Study
In the treatment of cocaine dependence,
to compare the efficacy of:
Group Drug Counseling Along (GDC) Cognitive Therapy (CT) plus GDC Supportive-Expressive (SE) Therapy plus GDC Individual Drug Counseling (IDC) Plus GDC
Background
New research (McCann & Li, 2012) has demonstrated that number of weeks abstinent during and after treatment can reveal significant differences in outcome between treatments, even when previous analyses found no differences.
Goal of Current Study To evaluate the merits of different methods for
measuring outcomes including: – End-of-study abstinence measures during the active
treatment of cocaine dependence. Thus, we explored the associations between
active treatment phase cocaine use outcomes and (1) measures of cocaine use across follow-up, and (2) broader measures of functioning during active treatment and follow- up.
Design of Study 6 months of treatment Maximum of 24 group sessions;
36 individual sessions Experienced and trained counselors/therapists N=487 patients randomized Assessments of drug use and functioning obtained
at baseline and monthly for 6 months Addiction Severity Index (ASI) used to measure
functioning in addiction-related domains. Urines and self-report of cocaine use obtained
weekly
Patient Sample
Average age = 34 years, range 19-59 77% males, 23% females 58% Caucasian 42% minority (primarily African American) 60% employed 70% live alone 81% crack users, 19% intra-nasal users 33% current alcohol dependence 29% cocaine-induced mood disorder
Attrition
15 of 36 individual sessions completed
10 of 24 group sessions attended
Despite this attrition from treatment: - 94% completed at least one post-randomization assessment - 83% completed a 9 or 12 month follow-up
Mean ASI Drug Use Composite
0.08
0.10
0.12
0.14
0.16
0.18
0.20
0.22
0.24
Intake 1 2 3 4 5 6
IDCCTSEGDC
Month
IDC significantly better than CT, SE, and GDC, P’s < 0.01
Percent of Patients Achieving Three Months Abstinence
36
22
17
25
0
5
10
15
20
25
30
35
40
IDC CT SE GDC
Question: How best to measure outcomein the treatment of cocaine dependence?
1. What measures of during-treatment cocaine use best predict end-of-treatment functional outcomes?
2. What measures of during-treatment cocaine use best predict drug use outcomes at follow-up?
3. What measures of during-treatment cocaine use best predict functional outcomes at follow-up?
ASI Scales at 12 Months
Within-Treatment Outcome Psych Family/Social Medical Legal Employment
Average times used cocaine past week .13* .09 -.05 .15** .14*
Max. consecutive days abstinent from cocaine from self-report
-.00 -.11 .04 -.10 -.05
Completely abstinent (urine + self-report) -.02 -.10 .07 -.08 -.03
4+ weeks of abstinence (urine + self-report) .02 -.05 -.05 -.14* .09
3+ weeks of abstinence (urine + self-report) -.03 -.03 -.09 -.16** -.10
2+ weeks of abstinence (urine + self-report) .02 -.06 .10 -.17** -.03
1+ weeks of abstinence (urine + self-report) -.02 -.07 -.04 -.15** -.05
Percent reduction in cocaine use from baseline to month 6 (self-report)
-.13* -.07 -.01 -.14* -.14*
50% reduction from baseline (yes/no) -.16** -.10 .00 -.17** -.06
% (of available) Negative Urines for cocaine -.04 -.06 -.01 -.12* .07
% (scheduled) Negative Urines for cocaine -.02 -.09 .04 -.15* -.03
Note. Partial correlations shown with treatment group, site, and baseline ASI scores as covariate. N’s vary from 337 to 363.
Within-treatment cocaine outcomes (months 1 to 6) predicting 12 month (after baseline) follow-up functioning
Drug Use Outcomes at 12 Months Within-Treatment Outcome
Mean (SD)or percent
Days Using Cocaine
Past Month
Abstinent past month
Abstinent past 3 months
ASI Drug Use
Average times used cocaine past week 0.75 (1.10) .27 -.27 -.25 .24
Max. consecutive days abstinent from cocaine from self-report
60.7 (63.7) -.22 .32 .40 -.27
Completely abstinent (urine + self-report) 11.8% -.18 .31 .38 -.21
4+ weeks of abstinence (urine + self-report) 51.3% -.15** .12* .15** -.14*
3+ weeks of abstinence (urine + self-report)58.8% -.17** .12* .15** -.14*
2+ weeks of abstinence (urine + self-report) 70.6% -.20 .16** .15** -.16**
1+ weeks of abstinence (urine + self-report) 81.9% -.14* .13* .13* -.15**
Percent reduction in cocaine use from baseline to month 6 (self-report)
67.7 (56.6) -.23 .26 .31 -.27
50% reduction from baseline (yes/no) 78.1% -.23 .25 .29 -.29***
% (of available) Negative Urines for cocaine0.67 (0.41) -.18** .25 .28*** -.23***
% (scheduled) Negative Urines for cocaine0.49 (0.32) -.20 .26 .28*** -.22***
Within-treatment cocaine outcomes (months 1 to 6) predicting 12 month (after baseline) drug use outcomes.
Note. Partial correlations shown with treatment group and site used as covariates. Baseline scores for ASI Drug Use Composite and Days Used Past Month also used as covariates for those outcomes. Sample sizes vary from 337 to 363 due to missing data.* p< .05. ** p< .01. p<.001.
McCann, DJ., & Li SH (2012). A Novel, Nonbinary Evaluation of Success and Failure Reveals Bupropion Efficacy Versus Methamphetamine Dependence: Reanalysis of a Multisite Trial. CNS Neuroscience & Therapeutics, 18, 414–418.
EOSA = end of study abstinence. e.g., 2+ weeks abstinent immediately prior to end of treatment
NOBWOS = number of beyond-threshold weeks of success. e.g., if threshold is 2 weeks abstinent prior to treatment end, patient has to achieve 3 or more weeks abstinent
We added:
Number of consecutive weeks of abstinence from the end of the study
Does Looking at Abstinence at the End of Treatment Help?
Drug Use Measures at 12 Months (after baseline)
McCann and LiWithin-Treatment Outcomes
Mean Mean(SD) or percent
Days Using Cocaine in Past Month
Abstinent during Past month
Abstinent during Past 3 months
ASI Drug UseComposite at 9
months
EOSA – 1+ wks 45.1% (n=152) -.04 .18** .17** .20***EOSA -2+ wks
24.3% (n=82) -.15** .22*** .25*** -.26***
EOSA -3+ wks 15.7% (n=53) -.12* .22*** .24*** -.18**EOSA – 4+ wks 12.2% (n=41) -.16** .22*** .26*** -.20***NOBWOS – 1+ wks 1.25 (3.81) -.15** .22*** .26*** -.20***NOBWOS – 2+ wks 1.00 (3.58) -.14* .21*** .24*** -.18***NOBWOS – 3+ wks 0.85 (3.35) .13* .20*** .23*** -.18**NOBWOS – 4+ wks
0.72 (3.14) -.13* .19*** .22*** -.17**
Number of consec. wks abstinent from endpoint
1.70 (4.01)
-.14**
.23***
.26***
-.22***
McCann and Li Within-treatment cocaine outcomes (months 1 to 6) predicting 12 month (after baseline) drug use measures
Note. EOSA = end of study abstinence. NOBWOS=number of beyond-threshold weeks of success.Partial correlations shown with treatment group and site used as covariates. Baseline scores for ASI Drug Use Composite and Days Used Past Month also used as covariates for those outcomes. N=337.p< .05. ** p< .01. p <.001.
EOSA=end of study abstinence.NOBWOS=number of beyond-threshold weeks of success. Lower ASI scores=fewer problems. * p < .05. ** p< .01
ASI Scales at 12 Months
Within-Treatment Outcome Psych Family/Social Medical Legal Employment
EOSA – 1+ wks -.00 -.04 .09 .02 .07
EOSA -2+ wks -.03 -.12 .08 -.05 -.01
EOSA -3+ wks -.07 -.08 .02 -.04 -.12*
EOSA – 4+ wks -.13* -.06 .01 -.01 -.09
NOBWOS – 1+ wks -.06 -.07 .03 -.02 -.08
NOBWOS – 2+ wks -.06 -.06 .02 -.01 -.08
NOBWOS – 3+ wks -.05 -.05 .02 -.01 -.07
NOBWOS – 4+ wks -.04 -.05 .03 -.01 -.07
Number of consec. wks abstinent from endpoint
-.05 -.07 .04 -.01 -.06
Within-treatment cocaine outcomes (months 1 to 6) predicting 12 month (after baseline) follow-up functioning.
Conclusions
■ Within-study cocaine use measures moderately associated with cocaine/drug use at 12 months.
- Abstinence based measures look best, urine samples showed no correlation except for legal problems
■ Within-study cocaine use measures not associated with functioning at treatment endpoint or at 1-year follow-up.
■ End of study abstinence weeks, and weeks beyond threshold
associated with cocaine use/abstinence measures at 1-year follow-up, but not functioning
- Count of weeks abstinence at end of treatment works as well
Conclusions
■ Drug use is episodic. Very few “intermittent users”, mostly continuous users and abstainers.
■ Some people function relatively well despite drug use.■ Unable to summarize outcome in one success/fail index.
Limitations■ Distributions of outcome measures■ Use of correlations to compare (but odds ratio better)■ Complete abstainers result in restrictive range of predictors■ Sample: patients with psychiatric comorbidities requiring
any psychotropic medications (including antidepressants) were excluded
■ Other functioning measures (outside of ASI) not included
18
Amphetamine Addiction in Iceland and Extended Release Injectable Ntx
Valgerður Rúnarsdóttir, M.D.,
Vogur Hospital Iceland
SAA National Center of Addiction Medicine
Ingunn Hansdóttir, PhD,
Assistant Professor University of Iceland
Research Counsil Member SAA National Center of Addiction Medicine
Symposium on Emerging Data on Efficacy and Clinical Applications of Extended Release Naltrexone Formulations,
presented at 75th Annual Meeting - College on Problems of Drug Dependence - June 15-20, 2013, San Diego, CA
19
Swedish studies
Jayaram-Lindstrom et al Am.J. Psychiatry, 2008 Significant effect using oral naltrexone in
ramdomized, placebo-controlled 12 week trial of 80 amphetmine dependent outpatients.
20
21
Icelandic setting
Centralized addiction treatment Good access to treatment Vogur hospital lynchpin in addiction trmt Population endorses disease concept Well trained staff Evidence based practice
22
Icelandic setting - Treatment as usual: Detox Hospitalization 7-10 days
Residential: 4 weeks
Intensive outpatient 5x week for 1 mo (60 hrs) 1x week for 3 mo (12 hrs)
Outpatient follow-up 2x week for 3 mo (24 hrs) 1x week for 9 mo (36 hrs)
Detox
7-10 days
Residential4 weeks
Outpatient intensive
Outpatient follow-up
23
Study Design -I
100 amphetamine dependent treatment seeking patients at Vogur Hospital
Randomized, double blind trial og 6 month trmt with VIVITROL® or VIVITROL®placebo and Treatment as usual
Stratified by gender and IV status. All participants detoxed at Vogur Hospital and
consented. Randomized before going to outpatient status.
24
Baseline diagnoses
DSM-IV checklist physician diagnosis
N (%)
Amphetamine dependence 100Alcohol dependence 75Cannabis dependence 69Cocaine dependence 26Methylphenidate dependence 15Sedative dependence 30Opiate dependence 0
25
RetentionNumber of subjects receiving study treatment
injection 1 injection 2 injection 3 injection 4 injection 5 injection 60
10
20
30
40
50
60
70
80
90
100100
72
56
47 46
37
TotalTreatmentPlacebo
Negative urines;%1247 urines collected (1194-/53+) 2400 urines target
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 240%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
Observed Treatment
Observed Placebo
Imputed Treatment
Imputed Placebo
27
% Drug Negative Urines(N=1257)
Amphetamine:: 4.25 Benzodiazepines: 8.26 Marijuana: 6.98 Cocaine: 1.44 Opioids: 0.96
28
Conclusions
Robust response to treatment as usual for those who stayed in trmt with no additional benefit from Naltrexone.
Different sample & more psychosocial rx than Swedish srudy
Trend towards worse outcome for those going directly to outpatient
Have not analyzed data as per McCann & Li