Experience in developing a tool using the CSSA as a model

Kyle M. Kampman M.D.Kyle M. Kampman M.D.

Professor Professor

Department of PsychiatryDepartment of Psychiatry

Perelman School of MedicinePerelman School of Medicine

University of Pennsylvania University of Pennsylvania

MOST Meeting 25 March 2015MOST Meeting 25 March 2015

Developing the CSSA as an outcome measureDeveloping 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

What is the CSSA?What is the CSSA?

CCocaine ocaine SSelective elective SSeverity everity AAssessmentssessment

- 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 changesappetite changes sleep changessleep changes

cocaine cravingcocaine craving depressed mooddepressed mood

anxietyanxiety irritability irritability

lethargylethargy inattention inattention

paranoiaparanoia heart rate changes heart rate changes

Where did the CSSA come from?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 Modeled on the Selective Severity Assessment for alcohol (Gross 1973)for alcohol (Gross 1973)

• Intended to assist in the management of Intended to assist in the management of cocaine withdrawal syndrome cocaine withdrawal syndrome

Cocaine withdrawal as a syndrome

Gawin and Kleber Arch Gen Psychiatry 1986;43:107-113

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

Cocaine withdrawal and subjective effects

Cocaine Withdrawal Increases the Cocaine High

Sofuoglu et al. Drug Alcohol Depend 2003; 69:273-282

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

The CSSA

18 Items

Interviewer administered

2 craving scales

One total score

Psychometric testingPsychometric testing

Initial reliability and validity testingInitial reliability and validity testing

1.1. Test retest reliabilityTest retest reliability

2.2. Interrater reliability Interrater reliability

3.3. Internal consistencyInternal consistency

4. Concurrent validity

5. Predictive validity

Kampman et al. Addict Behav. 1998 (4):449-61.

CSSA: concurrent validityCSSA: concurrent validity

Individual items correlate with DSM-IV criteriaIndividual items correlate with DSM-IV criteria

•Depressed moodDepressed mood

•LethargyLethargy

•Increased appetiteIncreased appetite

•Increased sleepIncreased sleep

•Irritability Irritability

CSSA: concurrent validityCSSA: concurrent validity

Individual items correlate with ASI severity measuresIndividual items correlate with ASI severity measures

–More days of cocaine useMore days of cocaine use

–Longer lifetime history of cocaine useLonger lifetime history of cocaine use

–Higher ASI Severity scores for drug problemsHigher ASI Severity scores for drug problems

CSSA: concurrent validityCSSA: concurrent validity

Specific to cocaine withdrawalSpecific to cocaine withdrawal

CSSA: concurrent validityCSSA: concurrent validity

Scores decline over time if a patient becomes abstinentScores decline over time if a patient becomes abstinent

CSSA: predictive validityCSSA: predictive validity

High CSSA Scores Predict Poor OutcomeHigh CSSA Scores Predict Poor Outcome1. Psychotherapy trial, University of Pennsylvania

Completed 30 Days of Treatment

Mulvaney et al., JSAT 1999;16(2):129-35.

*

* p = .005

CSSA: predictive validityCSSA: predictive validity

High CSSA Scores Predict Poor OutcomeHigh CSSA Scores Predict Poor Outcome2. Day Hospital, Philadelphia VAMC

Completed 30 Days of Treatment

Kampman et al. Psychol Addict Behav. 2001;15(1):52-9.

*

*p = .001

CSSA : predictive validityCSSA : predictive validity

High CSSA Scores Predict Poor OutcomeHigh CSSA Scores Predict Poor Outcome3. Medication Trial, University of Pennsylvania

3 Consecutive Weeks of Abstinence

Kampman et al., Addict Behav. 2002;27(2):251-60.

*

* p < .001

Identifying predictors in cocaine dependence treatmentIdentifying 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

Demographics and baseline drug use dataDemographics and baseline drug use data

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

(standard deviation)

Baseline predictors 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)

Age 4.1 .04 2.3 .13 .60 .44

Gender .80 .37 <.01 .99 .01 .91

Yrs education .89 .35 4.2 .04 .77 .38

Days coc. Use (past 30) 24.6 <.001 3.4 .06 21.5 <.001

Yrs coc use (lifetime) 1.2 .27 .07 .79 2.1 .14

Days alc. Use (past 30) .05 .82 3.2 .07 <.01 .99

Yrs alc use (lifetime) 3.3 .07 6.3 .01 4.1 .04

Initial UDS 23.9 <.001 8.1 .004 14.0 <.001

Initial CSSA score 16.5 <.001 8.4 .004 15.5 <.001

Bough et al. Neuropsychopharmacology. 2014;39(1):202-19

0

1

2

3

4

5

6

Low CSSA High CSSA

Amantadine Placebo

Number of Clean Urine Samples

CSSA and medication response: amantadineCSSA and medication response: amantadine

Amantadine Improved AbstinenceAmantadine Improved Abstinence

Kampman et al., Kampman et al., Am J Psychiatry. 2000;157(12):2052-4.Am J Psychiatry. 2000;157(12):2052-4.

CSSA and medication response: propranololCSSA and medication response: propranolol

Propranolol Improves Outcome in High CSSA PatientsPropranolol Improves Outcome in High CSSA Patients

RetentionRetention Urinary BE LevelsUrinary BE Levels

Kampman et al., Drug Alcohol Depend. 2001;63(1):69-78.

CSSA and medication response; topiramateCSSA and medication response; topiramate

Kampman et al. Drug Alcohol Depend. 2013;133(1):94-9.

CSSA as an outcome measureCSSA as an outcome measure

CSSA Scores in Treatment CSSA Scores in Treatment Mean CSSA scores tend to decline over time in medication trials

No differences in CSSA scores over time in several trialstopiramatemodafinilacamprosatenaltrexone (oral)naltrexone (extended release injectable)vareniclinepiracetamdisulfiramolanzapineginko bilobatheobromineamantadine*propranolol – reduced withdrawal symptoms in 1st trial not 2nd

DiscussionDiscussion

• The CSSA is an good predictor of outcome in outpatient The CSSA is an good predictor of outcome in outpatient cocaine dependence treatmentcocaine dependence treatment

• The CSSA may identify subgroups responsive to particular The CSSA may identify subgroups responsive to particular medications – propranolol and topiramate for examplemedications – propranolol and topiramate for example

• No medication tested has shown a differential response in No medication tested has shown a differential response in reducing CSSA scores.reducing CSSA scores.

Individual CSSA Items as PredictorsIndividual 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

Hypophagia 2.1 .14 1.3 .25 .3.6 .06

Carb. Craving 5.6 .02 .01 .93 ..40 .52

Coc. Crav. intensity 22.0 <.001 6.7 .009 17.6 <.001

Coc. Crav. frequency 17.0 <.001 4.7 .03 9.1 .003

Bradycardia 11.6 .001 3.5 .04 9.0 .003

Decreased Sleep 1.8 .18 .48 ..48 4.4 .04

Increased sleep 5.3 .02 .67 .412 4.3 .03

Anxiety .05 .83 4.0 .04 .19 .66

Cocaine craving and bradycardia were the most consistent predictors of outcome.

Predictors of psychosocial treatment outcomePredictors of psychosocial treatment outcome

RetentionOutpatient

N=87

RetentionDay Program

N=97

AbstinenceMed Trial

N=76

High CSSA Scores Predict Poor OutcomeHigh CSSA Scores Predict Poor Outcome

AbstinenceCoc/alcN= 80