Relationships with Long Term Cocaine Use and Functioning Brian D Kiluk PhD Kathleen M Carroll PhD Yale University School of Medicine Supported by NIDA Supplement to R01 DA15969 MOST Meeting March 25 2015 ID: 1033127
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1. Evaluating Cocaine Use Outcome Measures: Relationships with Long Term Cocaine Use and Functioning Brian D. Kiluk, Ph.D.Kathleen M. Carroll, Ph.D.Yale University School of MedicineSupported by NIDA Supplement to R01 DA15969MOST Meeting March 25, 2015
2. OverviewEvaluate 15 candidate cocaine use treatment outcome measuresPooled data across 5 RCTsCriteriaSensitivity to medication effectsSensitivity to behavioral therapiesRelationship with post-treatment cocaine useRelationship to measures of general functioningCarroll, Kiluk et al., (2014). Towards empirical identification of a clinically meaningful indicator of treatment outcome for drug addiction: Features of candidate indicators and evaluation of sensitivity to treatment effects and relationship to one year cocaine use follow-up outcomes. Drug and Alcohol Dependence, 137, 3-19.
3. Multiple cocaine treatment RCTs, 2000-presentStudy 1 “Cocaine-alcohol”Carroll, K.M., Nich, C., Ball, S.A., et al. 1998. Treatment of cocaine and alcohol dependence with psychotherapy and disulfiram. Addiction 93, 713-728.Carroll, K.M., Nich, C., Ball, S.A., et al. 2000. One year follow-up of disulfiram and psychotherapy for cocaine-alcohol abusers: Sustained effects of treatment. Addiction 95, 1335-1349.Study 2 “M&M”Carroll, K.M., Fenton, L.R., Ball, S.A.,et al. 2004. Efficacy of disulfiram and cognitive-behavioral therapy in cocaine-dependent outpatients: A randomized placebo controlled trial. Archives of General Psychiatry 64, 264-272.Study 3 “TSF/Disulfiram”Carroll, K.M., Eagan, D., Nich, C., et al. 2012,. Efficacy of Twelve Step Facilitation and disulfiram for cocaine-using methadone-maintained individuals. Drug and Alcohol Dependence , 126, 224-231Study 4 “CBT4CBT1”Carroll, K.M., Ball, S.A., Martino, S., et al. 2008. Computer-assisted cognitive-behavioral therapy for addiction. A randomized clinical trial of 'CBT4CBT'. American Journal of Psychiatry 165, 881-888.Carroll, K.M., Ball, S.A., Martino, S., et al. 2009. Enduring effects of a computer-assisted training program for cognitive-behavioral therapy: A six-month follow-up of CBT4CBT. Drug and Alcohol Dependence 100, 178-181 Study 5 “CM Disulfiram”Carroll, K.M., Nich, C., Petry, N.M., et al, under review. Disulfiram and contingency management to enhance CBT for cocaine dependence: effects on cocaine use and preliminary evidence for interactions with DBH polymorphism.
4. Common assessment approach 12 weeks outpatient treatmentBehavioral therapies manual guided with independent fidelity checksMedications placebo controlled with riboflavin checks1-3/x weekly urine toxicology screens1 year follow-up (15 months from randomization)Substance Use CalendarDay by day frequency of cocaine use during entirety of studyAverage 13% discrepancy from urine results (urine positive, self-report negative)Follow-ups with urine collection at 1, 3, 6, 12 months >80% of the intention to treat sampleAddiction Severity Index at each assessment
5. Common follow-up indicatorsMean days of cocaine use 1, 3, 6, and 12 month follow ups via Substance Use CalendarAbstinent throughout full follow-upComposite measure of ‘good outcome’ Days of employment problems = 0, Days of legal problems = 0, Days of psych problems=0, Days of cocaine use = 0
6. Study 1Clinical MangmtTSFCBTDisulfiram250 mg/dayNo medication121 cocaine- and alcohol dependent outpatients12 weeks1 year follow-upWeekly utoxManual guided, fidelity ratedRiboflavin for med complianceOutcomes:CBT, TSF > Clinical managementDisulfiram > no med
7. Study 2CBTIPTDisulfiramPlaceboN=121 cocaine dependent outpatients12 weeksUtox 1x week1 year follow-upManual-guided with fidelity ratingsDouble blind placebo control, riboflavinOutcomesCBT>IPTDisulif>placebo
8. Study 3TAUTAU + TSFDisulfiramPlaceboN=112 cocaine-dependent methadone maintained patients12 weeksUtox 3x week1 year follow-upManual-guided with fidelity ratingsDouble blind placebo control, riboflavinOutcomesTSF>TAU aloneNo medication effect
9. Study 4TAUTAU + CBT4CBTN=78 mixed substance users, outpatients, 38 cocaine users.8 weeks of treatment, 6 month follow-upUtox 2x weeklyOutcomesCBT4CBT>TAU alone
10. Study 5CBTCBT+CMDisulfiramPlaceboN=99 cocaine-dependent outpatients12 weeksUtox 3x week1 year follow-upManual-guided with fidelity ratingsDouble blind placebo controlOutcome:CM+CBT>CBT aloneNo main effect for disulfiram, interaction with DBH
11. Overview of trialsMedicationBehavtherapyN for follow-up sample (all > 80%)% female% ethnic minorityMean days cocaine use/past 28% not working% criminal justice referredStudy 1:Coc-Alcohol, Disulfiram v no medCBT v TSF v clinical management9129%60%1455%24%Study 2:M&MDisulfiram v placeboCBT vIPT1082535145722Study 3:TSF-Disulifram, Disulfiram v placeboTSF v no TSF112413616462Study 4:CBT4CBTNo medCBT4CBT vTAU38**477688042Study 5:CM-DisDisuflriam v placeboCM + CBT v CBT 85316014695TOTAL4343348135316
12. Outcomes across trialsDesignPlatformUrine schedule/% cocaine freeMean % days abstinent during tx% completely abstinent during treatment6 month follow-up % good outcome compositeCoc-Alcohol3 x 2 RCTOutpatientCoc+alcohol2x/55%85%19%13%2 M&M2 x 2 RCTOutpatientcocaine1x/68%8112133 TSF Dis2 x 2 RCTMethadonecocaine3x/18%605184 CBT4CBT 2 groupRCTOutpatientcocaine subgroup only2x/50%82924CM Disulf2 x 2 RCTOutpatient cocaine3X/44%761727
13. Medication effects across indicators No medication Placebo Disulfiram n=36 n=148n=212 Outcome IndicatorTypemean or Nsd or % mean or Nsd or % mean or Nsd or % F/X2pTukey/phiDays retained in treatment protocol C 37.532.1 53.735.6 58.332.6 6.26.00Disulf, Placebo >No medPercent negative cocaine urine specimensC42.641.1 37.536.0 38.936.8 0.37.70 Maximum consecutive days abstinentC19.518.6 19.123.4 25.726.2 3.2.04Disulf > PlaceboPercent days of abstinence from cocaineC83.118.0 76.425.3 70.926.9 5.61.00No med>PlaceboMaximum days of continuous abstinence during last two weeks of treatment*C 7.64.5 8.94.7 4.83.03Disulfiram > PlaceboCompletely abstinent last two weeks of treatmentD 1036% 2924% 7524% 10.39.01No med > Disulf, placebo3 or more weeks of continuous abstinenceD925% 6141%9344% 4.52.10 2 or more weeks of continuous abstinenceD1542% 6846%11353% 2.86.24 1 or more weeks of continuous abstinenceD2261% 10672%15875% 2.84.26 Completely abstinent from cocaine during treatmentD514% 1710%2914% 0.26.88 Completed treatment and abstinent in last weekD719% 3524% 7437% 8.27.02Disulf > no med% reduction (28 days prior/days last 4 weeks)C62.236.0 60.237.352.839.3 1.78.17 50% reduction in frequency of cocaine useD925% 0.5437%7033% 1.78.41 75% reduction in cocaine useD411% 2819%3617% 1.25.54 Report no cocaine use, legal, employment, or psychological problems last 28 days of treatment – ‘good outcome’D217% 1913% 1819% 1.18.55
14. Indicators across behavioral therapiesComparison (1)TSF (2)CBT (3)CM (4) n=195n=97n=105n=37 Outcome indicatorMean or nsd or %Mean or nsd or %Mean or nsd or %Mean or nsd or %F/ X2pTukeyDays retained in treatment protocol 54.233.156.93351.6330.8646.0834.051.13.34nsProportion cocaine negative urine specimens.36.37.26.29.49.38.56.388.130.001v3, 1v4 2v3, 2v4 Maximum consecutive days abstinent20.124.323.722.9725.723.5823.7627.721.26.29nsPercent days of abstinence .72.27.75.24.82.21.81.264.200.011v3 Maximum days of continuous abstinence during participant's last two weeks of treatment 8.14.77.94.539.354.3810.274.632.540.06nsCompletely abstinent last 2 weeks of treatment 5433%2427%4246%14.0054%11.61.0094 v other, 3 v 23+ weeks of continuous abstinence7438%3435%4543%27.0073%17.85.004 v other2+ weeks of continuous abstinence9046%4041%5754%29.0078%16.82.0014 v other1+ weeks of continuous abstinence13971%6668%7370%32.0071%4.85.18nsCompletely abstinent from cocaine during treatment2513%1111%1615%8.0024%3.55.31nsCompleting treatment and abstinent in last week5631%2628%3537%11.0030%2.15.54ns% reduction in frequency of cocaine use (28 days prior/days last 4 weeks)0.530.380.58.39.65.37.62.322.15.09ns50% reduction60.031%2627%3836%15.0041%3.43.33ns75% reduction2312%99%2524%12.0032%18.12.003 v other, 4 v other‘Good outcome’ 2011%812%56%9.0024%8.9.034 v other
15. Outcome indicatorDays of Cocaine Use in Follow-Up MonthComplete Abstinence in FUGood Functioning Status at Follow-Up Month1361213612Days retained in treatment protocolr-.12-.06-.08.02.05.10.05.08.04p .01.23.09.76.33.04.35.12.47Percent cocaine negative urine specimensr-.31-.28-.30-.16.33.33.29.25.22p .00.00.00.01.00.00.00.00.00Maximum consecutive days of abstinencer-.30-.24-.26-.12.30.34.26.24.17p .00.00.00.02.00.00.00.00.00Percent days of abstinencer-.39-.37-.35-.24.19.23.21.18.14p .00.00.00.00.00.00.00.00.01Maximum days of consecutive abstinence during last two weeks of treatmentr-.46-.35-.30-.21.32.31.33.19.24p .00.00.00.00.00.00.00.00.00Completely abstinent last two weeks of treatmentr-.30-.25-.19-.07.28.29.31.21.19p .00.00.00.25.00.00.00.00.003+ weeks of abstinencer-.33-.30-.28-.16.25.26.26.24.24p .00.00.00.00.00.00.00.00.002+ weeks of abstinencer-.26-.26-.28-.14.24.24.26.22.20p .00.00.00.01.00.00.00.00.001+ week of abstinencer-.27-.22-.24-.10.11.21.17.15.17p .00.00.00.05.02.00.00.00.00Completely abstinent during treatmentr-.14-.08-.11-.09.23.28.17.14.19p .00.12.03.09.00.00.00.00.00Completed treatment and abstinent in the last weekr-.30-.24-.22-.09.23.22.23.19.12p .00.00.00.09.00.00.00.00.03% reduction in frequency of cocaine user-.32-.26-.22-.11.18.24.22.17.14p .00.00.00.07.00.00.00.00.0150% reductionr-.02-.01.02.04-.16-.04-.05-.09.00p .65.76.67.49.00.40.30.06.9475% reductionr-.08-.07-.04-.01-.11-.04.00-.01.07p .08.14.42.92.02.39.94.88.21Good outcomer-.20-.20-.15-.08.29.37.28.24.21p .00.00.00.16.00.00.00.00.00Relationship with Post-Treatment Cocaine Use and Functioning
16. Outcome IndicatorSensitivity to disulfiram effectsSensitivity to behavioral therapiesRelationship with post tx cocaine useRelationship to measures of general functioning/Days retained in treatment protocol XPercent negative cocaine urine specimensXXXMaximum consecutive days abstinentXXXPercent days of abstinence from cocaineXXXMaximum days of continuous abstinence during last two weeks of treatmentXXXCompletely abstinent last two weeks of treatmentXXXX3 or more weeks of continuous abstinenceXXXX2 or more weeks of continuous abstinenceX1 or more weeks of continuous abstinenceCompletely abstinent from cocaine during treatmentCompleted treatment and abstinent in last weekXX% reduction (28 days prior/days last 4 weeks)X50% reduction in cocaine use75% reduction in cocaine useX“Good outcome” XXX
17. Does cocaine abstinence have effect on functional problems?Evaluate the relationship between within-treatment cocaine use and problems in major life areas other than cocaine use (e.g., medical, legal, employment, family/social, psychological) following treatment Latent growth curve model to evaluate within-tx cocaine use on change in ‘global problems’ over timeKiluk, B.D., Nich, C., Witkiewitz, K., Babuscio, T.A., & Carroll, K.M. (2014). What happens in treatment doesn’t stay in treatment: Cocaine abstinence during treatment is associated with fewer problems at follow-up. Journal of Consulting and Clinical Psychology, 82, 619-627.
18. ‘Global Problems’ constructCreated latent measure of ‘global problems’Used longitudinal confirmatory factor analysis to evaluate equivalence of ASI problem subscales over timeUsed ‘Days of Problems’ item rather than composite scoreExamined whether factor structure was metric invariant over timeUnconditional latent growth curve modeling used to examine changes in ‘global problems’ over timeConditional latent growth curve modeling used to examine association between within-tx cocaine use and follow-up levels of global problems over time (controlling for baseline problems)
19. Latent growth curve model of within-tx cocaine use and change in global problems during follow-up periodβ = -.43**β = -.17**β = .32**** p<.001
20. Summary, so farExisting widely used continuous measures are consistent predictors of cocaine use and good general functioning in follow up: Percent days abstinent, maximum days of consecutive abstinence, percent positive urines, max days abstinence in last 2 weeksGood performance of urine measures and abstinence at termination measures offset by limits to availability of data (80% of samples)Poorer performance for ‘reduction’ measures, as well as ‘complete abstinence during treatment”End of treatment abstinence, 3+ weeks abstinence very consistent predictor of long term cocaine use and functioning, sensitive to effects of medication and behavioral therapiesHigher levels of cocaine abstinence during tx associated with fewer problems during follow-up (controlling for baseline level of problems)