1. Experience in developing a tool using the CSSA as a model Kyle M. Kampman M.D. Professor Department of Psychiatry Perelman School of Medicine University of Pennsylvania MOST Meeting 25 March 2015

2. Developing the CSSA as an outcome measure What is the CSSA?What is the CSSA? Where did it come from?Where did it come from? What does it measure?What does it measure? Basic reliability and validity testingBasic reliability and validity testing Subsequent testing and usefulness in clinical trialsSubsequent testing and usefulness in clinical trials

3. What is the CSSA? Cocaine Selective Severity Assessment - It is a measure of cocaine withdrawal - It is a measure of cocaine withdrawal - 18 Item each measured on a 0-7 scale - 18 Item each measured on a 0-7 scale - Signs and symptoms measured include: - Signs and symptoms measured include: appetite changessleep changes appetite changessleep changes cocaine cravingdepressed mood cocaine cravingdepressed mood anxiety irritability anxiety irritability lethargy inattention lethargy inattention paranoia heart rate changes paranoia heart rate changes

4. Where did the CSSA come from? CSSA written by Joe Volpicelli at Penn CSACSSA written by Joe Volpicelli at Penn CSA Modeled on the Selective Severity Assessment for alcohol (Gross 1973)Modeled on the Selective Severity Assessment for alcohol (Gross 1973) Intended to assist in the management of cocaine withdrawal syndromeIntended to assist in the management of cocaine withdrawal syndrome

5. Cocaine withdrawal as a syndrome Gawin and Kleber Arch Gen Psychiatry 1986;43:107-113

6. Cocaine withdrawal and subjective effects Depression increases cocaine high (Uslaner, 1999; Sofuoglu, 2001) Irritability increases cocaine high (Newton, 2003) Cocaine Withdrawal Increases the Cocaine High

7. Cocaine withdrawal and subjective effects Cocaine Withdrawal Increases the Cocaine High Sofuoglu et al. Drug Alcohol Depend 2003; 69:273-282

8. Cocaine withdrawal and hedonic dysregulation Several studies report that the presence of severe cocaine withdrawal symptoms at baseline predicts poor clinical outcome Craving Hedonic Dysregulation WD

9. The CSSA 18 Items Interviewer administered 2 craving scales One total score

10. Psychometric testing Initial reliability and validity testing 1.Test retest reliability 2.Interrater reliability 3.Internal consistency 4.Concurrent validity 5.Predictive validity Kampman et al. Addict Behav. 1998 (4):449-61.

11. CSSA: concurrent validity Individual items correlate with DSM-IV criteria Depressed moodDepressed mood LethargyLethargy Increased appetiteIncreased appetite Increased sleepIncreased sleep IrritabilityIrritability

12. CSSA: concurrent validity Individual items correlate with ASI severity measures –More days of cocaine use –Longer lifetime history of cocaine use –Higher ASI Severity scores for drug problems

13. CSSA: concurrent validity Specific to cocaine withdrawal Specific to cocaine withdrawal

14. CSSA: concurrent validity Scores decline over time if a patient becomes abstinent Scores decline over time if a patient becomes abstinent

15. CSSA: predictive validity High CSSA Scores Predict Poor Outcome 1. Psychotherapy trial, University of Pennsylvania Completed 30 Days of Treatment Mulvaney et al., JSAT 1999;16(2):129-35. * * p =.005

16. CSSA: predictive validity High CSSA Scores Predict Poor Outcome 2. Day Hospital, Philadelphia VAMC Completed 30 Days of Treatment Kampman et al. Psychol Addict Behav. 2001;15(1):52-9. * *p =.001

17. CSSA : predictive validity High CSSA Scores Predict Poor Outcome 3. Medication Trial, University of Pennsylvania 3 Consecutive Weeks of Abstinence Kampman et al., Addict Behav. 2002;27(2):251-60. * * p <.001

18. Identifying predictors in cocaine dependence treatment Subjects and measures 7 clinical trials 7-12 weeks duration Cocaine dependent only ASI, UDS 2-3 weekly, TLFB self-report Predictor variables Baseline ASI Baseline UDS CSSA scores Outcome variables Three weeks of continuous abstinence 50% reduction ASI Composite Drug Score No self reported cocaine use last 4 wks of the trial

19. Demographics and baseline drug use data N 402 Age 39 (6.8) % African-American 81% % men 75% Years of education 13 (1.9) % crack smokers 87% Days coc. use (past 30) 13 (9.3) Years coc. Use (lifetime) 9.9 (6.0) $ for drugs (past 30) $606 (850) ASI Comp. Drug Score.230 (.08) CSSA score 27 (18) (standard deviation)

20. Baseline predictors. 3 Weeks of Continuous Cocaine Abstinence Model  2 (P) 50% Reduction in ASI Composite Drug Scores Model  2 (P) Self-Reported Abstinence, Last 4 Weeks of Treatment Model  2 (P) Age4.1.042.3.13.60.44 Gender.80.37<.01.99.01.91 Yrs education.89.354.2.04.77.38 Days coc. Use (past 30)24.6<.0013.4.0621.5<.001 Yrs coc use (lifetime)1.2.27.07.792.1.14 Days alc. Use (past 30).05.823.2.07<.01.99 Yrs alc use (lifetime)3.3.076.3.014.1.04 Initial UDS23.9<.0018.1.00414.0<.001 Initial CSSA score16.5<.0018.4.00415.5<.001 Bough et al. Neuropsychopharmacology. 2014;39(1):202-19

21. 0 1 2 3 4 5 6 Low CSSAHigh CSSA AmantadinePlacebo Number of Clean Urine Samples CSSA and medication response: amantadine Amantadine Improved Abstinence Kampman et al., Am J Psychiatry. 2000;157(12):2052-4.

22. CSSA and medication response: propranolol Propranolol Improves Outcome in High CSSA Patients Retention Urinary BE Levels Kampman et al., Drug Alcohol Depend. 2001;63(1):69-78.

23. CSSA and medication response; topiramate Kampman et al. Drug Alcohol Depend. 2013;133(1):94-9.

24. CSSA as an outcome measure CSSA Scores in Treatment Mean CSSA scores tend to decline over time in medication trials No differences in CSSA scores over time in several trials topiramate modafinil acamprosate naltrexone (oral) naltrexone (extended release injectable) varenicline piracetam disulfiram olanzapine ginko biloba theobromine amantadine *propranolol – reduced withdrawal symptoms in 1 st trial not 2 nd

25. Discussion The CSSA is an good predictor of outcome in outpatient cocaine dependence treatmentThe CSSA is an good predictor of outcome in outpatient cocaine dependence treatment The CSSA may identify subgroups responsive to particular medications – propranolol and topiramate for exampleThe CSSA may identify subgroups responsive to particular medications – propranolol and topiramate for example No medication tested has shown a differential response in reducing CSSA scores.No medication tested has shown a differential response in reducing CSSA scores.

26. Individual CSSA Items as Predictors. 3 Weeks of Continuous Cocaine Abstinence Model  2 (P) 50% Reduction in ASI Comp. Drug Scores Model  2 (P) Self-Reported Abstinence, Last 4 Weeks of Treatment Model  2 (P) Hyperphagia.18.66.27.59.17.68 Hypophagia2.1.141.3.25.3.6.06 Carb. Craving5.6.02.01.93..40.52 Coc. Crav. intensity22.0<.0016.7.00917.6<.001 Coc. Crav. frequency17.0<.0014.7.039.1.003 Bradycardia11.6.0013.5.049.0.003 Decreased Sleep1.8.18.48..484.4.04 Increased sleep5.3.02.67.4124.3.03 Anxiety.05.834.0.04.19.66 Cocaine craving and bradycardia were the most consistent predictors of outcome.

27. Predictors of psychosocial treatment outcome Retention Outpatient N=87 Retention Day Program N=97 Abstinence Med Trial N=76 High CSSA Scores Predict Poor Outcome Abstinence Coc/alc N= 80