1. THE BRAVE NEW WORLD OF COMPUTERIZED INTERVENTIONS FOR ADDICTION KATHLEEN.CARROLL@YALE.EDU PSYCHOTHERAPY DEVELOPMENT CENTER WEBSITE: PDC.YALE.EDU NIDA R3715969, K05-DA00457, U10 - 015831 & P50 DA09241 DISCLOSURE: DR. CARROLL IS A MEMBER IN TRUST OF CBT4CBT LLC KATHLEEN.CARROLL@YALE.EDU

2. OVERVIEW 1. Development and of computerized CBT 2. How could web-based interventions improve how we treat addiction? Dissemination and accessibility Tailored treatments

3. THE NIH STAGE MODEL, 2014 ONKEN, CARROLL, SHOHAM, CUTHBERT & RIDDLE; PSYCHOLOGICAL SCIENCE, 2, 22-24.

4. COGNITIVE-BEHAVIORAL THERAPY CBT Based on functional analysis of substance use Emphasis on learning/implementation of coping skills Functional analysis and patterns of use Coping with craving Addressing ambivalence and coping with thoughts Refusal skills Seemingly irrelevant decisions Problem solving skills

5. Point (0) Delayed emergence Of effects

6. HOW SUCCESSFUL HAVE WE BEEN IN MOVING EVIDENCE BASED THERAPIES INTO CLINICAL PRACTICE? Programs, clinicians report high levels of use of empirically supported approaches, including CBT Increased pressure to do so by payors NO actual data from session tapes ….till now…

7. ANALYSIS OF 379 TAPES OF “STANDARD TREATMENT” WHAT INTERVENTIONS NEVER OCCURRED IN TAU? Percent of sessions where adherence score =1

8. FREQUENCY OF ‘CHAT’ BY TREATMENT CONDITION: CTN MET VS TAU

9. STAGE III LEADS BACK TO STAGE I: DISSEMINATION BACK TO DEVELOPMENT Manualized Treatment (CBT) Delivered through clinician Low ‘dose’ of CBT

10. WHY COMPUTER FACILITATED DELIVERY OF EVIDENCED BASED TREATMENTS ? **Effective implementation of CBT very rare in clinical practice Only a small fraction of people with addiction-related problems access treatment Save clinicians time, use as clinician extenders Broadly accessible, available 24/7 Facilitated delivery via multimedia presentation Standardization, quality control Individualization, repetition, flexibility Facilitation of systematic evaluation of components (moderators & mechanisms of action)

11. CORE PRINCIPLES: CBT4CBT DEVELOPMENT Highly engaging-capture attention of substance users, retain them in treatment Deliver potent dose of evidence based cognitive and behavioral strategies-focus on key generalizable skills Durability of effects-skills practice Modeling-demonstration of skills in realistic situations under stress Breadth of users-all drugs, balance of gender and ethnicity Security- NO identifying information or protected informantion

12. ‘CBT 4 CBT’ COMPUTER BASED TRAINING FOR CBT 7 modules, ~1 hour each, high flexibility Highly user friendly, no text to read, linear navigation Based on NIDA CBT manual Multiple strategies for presenting skills Video examples of characters struggling real life situations Repeat movie with character using skills to change ‘ending’ Interactive exercises, quizzes Multiple examples of ‘homework’

14. OVERVIEW: FIRST RANDOMIZED CLINICAL TRIAL 8 week randomized clinical trial Outpatient community treatment program Standard treatment (weekly individual + group therapy) (TAU) vs. CBT4CBT + TAU CBT4CBT offered in up to 2 weekly sessions 6 month follow-up Carroll et al., Am J Psychiatry, 2008

15. PARTICIPANTS, FIRST TRIAL, N=77 “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

16. PRIMARY OUTCOME (% DRUG- POSITIVE URINE TOXICOLOGY SCREENS), 8 WEEKS Carroll et al., 2008, Am J Psychiatry

17. PRIMARY OUTCOME: LONGEST CONSECUTIVE ABSTINENCE, IN DAYS, AT 8 WEEKS BY TREATMENT Carroll et al., 2008, Am J Psychiatry

18. SKILL LEVEL THOUGH 6 MONTH FOLLOW-UP: QUALITY OF BEST RESPONSE BY CONDITION Kiluk et al, Addiction, 2010

19. DURABILITY OF EFFECTS: 6 MONTH FOLLOW-UP Carroll et al., 2009, Drug & Alcohol Depend

20. QUALITY OF COPING SKILLS AS MEDIATOR OF OUTCOME IN CBT4CBT CBT v TAU % positive urine Coping Skills (1) b=5.2* (4) b=3.3 (2) b=.3* (3) b=8.3** Kiluk et al, Addiction, 2010

21. COST EFFECTIVENESS: COMPARISON ACROSS TREATMENTS AND STUDIES, OLMSTEAD ET AL., DAD, 2010 ( OUTCOME=LONGEST DAYS ABSTINENCE (LDA) INCREMENTAL COST EFFECTIVENESS RATIOS (ICERS) TreatmentBase Case ($) Favorable Scenario ($) CBT4CBT50-31 MET/CBT a 10277 Prize CM – MM b 141115 Prize CM – DF c 258163 a MET/CBT = motivational enhancement therapy + clinician-delivered CBT b Prize CM – MM = prize-based contingency management in methadone clinics c Prize CM – DF = prize-based contingency management in drug free clinics

22. OVERVIEW: SECOND RANDOMIZED TRIAL 101 DSM-IV cocaine-dependent methadone maintained opioid users population Standard methadone maintenance (TAU) vs. CBT4CBT + TAU CBT4CBT offered in up to 2 weekly sessions, 6 month follow-up Sample: 60% female, 40% minority, 89% unemployed, higher levels psychiatric comorbidity (29% depressive disorder, 30% anxiety disorder), multiple other substance use Carroll et al., Am J Psych. 2014

23. PRIMARY POST TREATMENT OUTCOMES: COCAINE-MMP SAMPLE Carroll et al., AJP, 2014

24. STATUS: CBT4CBT Completed: 2 RCTs indicating efficacy and durability of CBT4CBT No treatment related adverse effects Variety of populations: Outpatient, methadone maintenance, and VA Demonstration of skill acquisition, cost effectiveness and durability Ongoing: P50 Center: Enhance CBT4CBT outcome with galantamine (placebo controlled RCT), fMRI, neurocog, genetics Evaluation of HIV module on drug/sex risk reduction Man versus Machine: CBT4CBT versus traditional therapist delivery Neural mechanisms of the Sleeper Effect Validation of alcohol-only version Randomized trial of Spanish version

25. DEMO: CBT4CBT.com

26. INNOVATORS/EARLY ADOPTERS, JUNE 2014-PRESENT Clinical: Mass General Hospital; IOP Clinical: Mercy Hospital, Springfield Mo Pilot; Montana Drug Courts RCT pilot, Zuni of New Mexico RCT pilot, UCLA primary care practice RCT, Prince Edward Island RCT (pending), Columbia U HIV clinics

27. POTENTIAL APPLICATIONS OF COMPUTER- ASSISTED THERAPIES ‘Clinician extenders’ Extending treatment benefits/ links to aftercare ‘Extending clinician expertise (e.g., dual diagnoses) Address overlooked issues (smoking) Linking systems of care (SBIRT) Behavioral platforms for pharmacotherapies Reaching rural opioid users (tele-buprenorphine) Homework apps for coaching Early intervention/prevention for mild cases TARGETING FUNDAMENTAL PROCESSES

28. NEW DIRECTIONS-PDC YEARS 21-26 “NEUROPLASTICITY REPRESENTS A PLAUSIBLE BIOLOGICAL MECHANISM THROUGH WHICH PSYCHOLOGICAL INTERVENTIONS MAY EXERT SOME OF THEIR THERAPEUTIC EFFECTS” Project 1: Kiluk/Carroll; Does cognitive control training prior to CBT enhance learning & outcome? Preparation (4 week) 1. TAU 2. CM/abstinence 3. CM+cognitive control training - Treatment (8weeks) CBT4CBT Neurocog + fMRI Neurocog + fMRI Neurocog + fMRI+ 6 month follow-up

29. Changes in brain activity via fMRI: Comparison of Post- to Pretreatment, CBT4CBT versus TAU Stroop related activity dlPFC decreases from pre- to post- CBT4CBT but not TAU X-=21pFWE=.05 CBT Stroop Post > Pre TAU Stroop Post > Pre

30. CATEHOL-O-METHYLTRANSFERASE GENE VAL158MET POLYMORPHISM (COMT) & TREATMENT OUTCOME N=82/101

31. EMOTIONAL (COCAINE) STROOP BY TREATMENT CONDITION (N=101)

32. PROJECT 3: HEDY KOBER CRAVING TASK  TREATMENT Regulation of craving Training-cognitive 3x/week 4 weeks 1 month follow -up Assessment only Regulation of craving training -mindfulness 3x/week 4 weeks Neurocog + fMRI Neurocog fMRI

33. RECONNECTING CBT WITH COGNITIVE SCIENCE: CBT=COGNITIVE CONTROL TRAINING ConceptTarget/Assesment example Intervention concept Regulation of cravingDistress tolerance, ROCROC training Attentional biasIATAttentional bias training Poor decision makingImpulsive responding/BART/EDT Delay discounting Problem solvingCANTAB, PFC tasksProblem solving, executive function Functional analysisSelf-monitoringWorking memory, CognitionsCognitive/affective awareness PASAT

34. THANKS. Co-Investigators Luis Anez, Sam Ball, Dianne Duffey, Brian Kiluk, Donna LaPaglia, Steve Martino, Katie Nuro, Todd Olmstead, Manny Paris, Nancy Petry, Julia Shi, Michelle Silva, Caroline, Mehmet Sofuoglu, Dawn Sugarman, Kelly Serafini, & Bruce Rounsaville Team: Melissa Gordon, Theresa Babuscio, Matt Buck, Donna Cofrancesco, Joanne Corvino, Karina Danvers, Kay Debski, Kathleen Devore, Liz Doohan, Dorothy Eagan, Tami Frankforter, Karen Hunkele, Dave Iamkis, Dan Marino, Cindy Morgan, Charla Nich, Galina Portnoy, Liz Vollono, fMRI component: Marc Potenza, Hedy Kober, Elise Devito, Patrick Worhunsky, Iris Balodis, Jiansong Xu, Jud Brewer, Sara Yip, Cameron DeLeone, Maggie Mae Mell, Todd Constable Yale Media: Rick Leone, Craig Tomlin, Thom Stylinski & Lucas Swineford Clinical performance sites: RNP: John Hamilton, Tina Klem, Joanne Montgomery, APT: Lynn Madden, Nicole Belisle, Amanda Shackle, CMHC: Bob Cole, Luis Anez, Donna LaPaglia