Transcript Woody - CTN Dissemination Library

Addiction and Evidence-Based
Treatments from the CTN
George Woody, MD
Department of Psychiatry
Perelman School of Medicine
University of Pennsylvania
Disclosures
• Fidelity Capital provided naltrexone implants
(Prodetoxon®) at reduced cost in Russia
• Alkermes provided Vivitrol ® for Iceland study
• Reckitt Benckiser provided Suboxone ® for CTN
study and one in Republic of Georgia
• Janssen providing Vivitrol ® at reduced cost for
Russian study
Background
 CTN established in 1998 following Institute
of Medicine Report
 Report found that evidence-based
therapies were not being widely used
 Recommended testing treatments that had
been effective in university-based studies,
in community treatment programs
 Overall aim: Involve treatment providers in
clinical trials to improve treatment
Background (continued)
• Funded 16 “Nodes”
• Node = university-based addiction treatment
research staff + community treatment programs
• Mostly on east and west coast
• Studies & sites selected for randomized trials of
promising treatments
• CTN infrastructure provided platform for
developing new studies & training fellowships
– “Engage” study at Christina
– International studies & training programs
The CTN Trials (1999-now)
Pending,
Development &
Review
CTN 0022
CTN 0023
CTN 0024
CTN 0025
CTN 0026
CTN 0048
CTN 0049
CTN 0050
CTN 0051
CTN 0052
B. Tai 2013
Data
Collection
CTN 0037
CTN 0044
CTN 0046
CTN 0047
Data Analysis
CTN 0027
CTN 0031
36 Multisite studies address:
• Pharmacotherapies
• Behavioral Interventions
• Integrated Therapies
• HIV/HCV
• Surveys
Publication &
Dissemination
CTN 0001
CTN 0002
CTN 0003
CTN 0004
CTN 0005
CTN 0006
CTN 0007
CTN 0008
CTN 0009
CTN 0010
CTN 0011
CTN 0012
CTN 0013
CTN 0014
CTN 0015
CTN 0016
CTN 0017
CTN 0018
CTN 0019
CTN 0020
CTN 0021
CTN 0028
CTN 0029
CTN 0030
CTN 0032
Basic Approach
• Most studies test something (MET, MI,
medication) added to usual treatment
• Aim is to see if study treatment improves
outcomes from usual treatment
• Implication:
– Interventions that are effective is university-based
studies will be effective in community treatment
– When shown effective, and done with participation of
treatment programs, will be more widely adopted and
outcomes improved
What Is “Usual” Treatment?
• Dominated by 12-Step approach
• Developed outside medical establishment
• Recovering community exists with MANY individuals that
have benefitted from 12-Step approaches
• 12-Step delivered in many contexts (residential, IOP,
TCs, regular OP, followup)
• Original advice of 12-Step founders was to work with
medical establishment
• Over time, “no medication” approach emerged, an idea
that diverges from advice of 12-Step founders
– This attitude gradually “mellowing”, but slowly
Additions/Developments to Usual Treatment
• Methadone maintenance
– Original target was chronically addicted adults
– Ambivalently accepted
– But, VERY helpful to thousands of patients
– Suboxone
• More flexible & safer than methadone
• 425,000 to 450,000 receiving buprenorphine product
every day in U.S.
• CB, MET, MI, relapse prevention
• Addiction treatment as HIV prevention
• 12-Step facilitation
• Extended release naltrexone
Most Recent Focus
• Integrate substance abuse interventions into general
health care
– Screening & brief interventions in primary care (SBIRT)
– Suboxone maintenance in HIV & primary care settings
– Identify untreated substance users on hospital units and use
peer counselors or social workers (“patient navigators”) to get
them into treatment (“Project Engage”)
• Use electronic medical records to study outcomes
• Drug courts and addiction treatment with
probationers/parolees or in jails of prisons
CTN Has or is Conducting Studies in All of These
Areas. Study Results Can Be Grouped Into 3
Categories Based on Magnitude of Effects
• Large
– Buprenorphine studies
– Extended release naltrexone
– Group-focused, skills training HIV risk reduction for women
• Moderate/Mild
– Motivational incentives/contingency management
– MET/MI
• No effect of study intervention; everybody improves
- OROS MPH when added to CB for adolescents with ADHD
- Brief Strategic Family Therapy
- 12-Step facilitation
- HIV risk reduction counseling with HIV testing
Buprenorphine vs Clonidine:
detoxification in community settings
Walter Ling MD
ISAP/UCLA
[email protected]
Percent Present and Clean
0001 (Inpatient)
100
90
80
70
60
Clonidine
Bup/Nx
50
40
30
20
10
0
Day 3 or 4
Day 7 or 8
Day 10 or 11 Day 13 or 14
Percent Present and Clean
0002 (Outpatient)
50
45
40
35
30
Clonidine
Bup/Nx
25
20
15
10
5
0
Day 3 or 4
Day 7 or 8
Day 10 or 11 Day 13 or 14
Adjunctive Counseling During Brief and Extended
Buprenorphine-Naloxone Treatment for Prescription Opioid
Dependence: A 2-Phase Randomized Controlled Trial
Weiss R, Potter J, Fiellin D, et al
Arch. Gen. Psychiatry 2011;68(12):1238-1246
2-Phase Study
Phase 1: Randomized 653 primarily opioid dependent to 2week bup-nal stabilization followed by 2-week dose taper
with followup at 8 weeks
Successful patients exited the study
Only 6.6% were successful
Prescription Opioid Addiction: Phase 2
• Unsuccessful patients randomized to 12-weeks
buprenorphine-naloxone with standard medical
management (SMM), or the same + weekly
counseling
• Results:
– No incremental effect with counseling
– 49.2% successful outcomes while on bup-naloxone
– 8.6% successful at week 8 followup
• Conclusion: Don’t be in a hurry to stop bup-nal
CLINICAL TRIALS NETWORK
Buprenorphine/Naloxone
Treatment for Opioid Addicted
Youth
Target: 15-21
University of Pennsylvania
And the
National Institute on Drug Abuse
Screening
Assent/Consent
Eligible
Not Eligible
End of
process
Randomization:
(within clinics)
DETOX
Detox over 2 wks
All Get Psycho/Soc Rx
2x weekly for 12 Wks
BUPNAL
for 12 wks
Taper starts wk 9;
Ends wk 12
Evaluations: weekly X 12 wks
Comprehensive @ 4, 8, 12, 24, 36 and 52 wks
Opioid Positive Urines:
Missing excluded (N=90)
100
90
DTX
BUP
80
70
60
50
40
30
20
10
Group Effect = p<.001
Time Effect = NS
Time X Group = p<.07
0
Baseline
Week 4
Week 8
Week 12
Conclusion
 Though young, only addicted for
average of 1.5 years, don’t be in a hurry
to stop bup-naloxone
 Same finding as prescription opioid
addiction study
How About Naltrexone?
• Binds tightly to mu-opioid receptors
• Approved as 50 mg tablet in 1970’s but
ineffective for most patients due to lack of
patient interest and adherence problems
– Exceptions: highly motivated patients; persons on
probation or parole exceptions
• Extended release formulations developed to
reduce adherence problem
• Main studies done in Russia
DOUBLE BLIND RANDOMIZED PLACEBO
CONTROLLED STUDY OF EFFECTIVENESS
OF IMPLANTABLE NALTREXONE
(PRODETOXON) FOR TREATMENT OF
HEROIN ADDICTION
Е. Krupitsky, E. Zvartau, V. Egorova, D.
Masalov, А. Burakov, М. Tsoy, N. Bushara, Т.
Romanova, Е. Verbitskaya, C. О’Brien, G. Woody
St.-Petersburg Pavlov State Medical University,
St.-Petersburg V.M.Bekhterev Research
Psychoneurological Institute,
University of Pennsylvania
NIDA Grant R01-DA-017317; K05 & CTN U10 awards
Kaplan-Meier Survival Functions: Drop out
Log Rank (Mantel-Cox) Sig.
P(PO+IN)- (PO+PI)<0,001
P(ON+PI)- (PO+PI)=0,069
Vivitrol for Opioid Addiction
Treatment
Krupitsky E, Zvartau E, et al
St.-Petersburg Pavlov State Medical University, St.Petersburg andV.M.Bekhterev Research
Psychoneurological Institute Multisite study
Double-blind, randomized, 6- month trial of Vivitrol vs.
Vivitrol placebo
Published in Lancet
Resulted in FDA approval of Vivitrol for preventing
relapse to opioid addiction
Response Profile
Cumulative % of Participants at Each Rate of Weekly
Confirmed Abstinence: XR-NTX 380 mg vs. Placebo
 Total abstinence (100% opioid-free weeks) during Weeks 5-24 was reported in 45 (35.7%)
of subjects in the XR-NTX group versus 28 (22.6%) subjects in placebo group (P=0.0224).
HIV/STD Sexual Risk Reduction Groups for
Women in Substance Abuse Treatment
Tross S, Campbell A, Cohen L, Calsyn D et al.
J. Acq. Immun. Def. Synd. 2008; 48(5):581-589
515 women with recent episode of unprotected sex
randomized to:
- Usual risk reduction counseling, or
- Five, 90-minute group problem-solving and skills
rehearsal sessions focused on reducing HIV
sexual risk
Results
• Main outcome: number of unprotected sex
acts at followup
• Significant differences between groups at
3 and 6 months (P <.0001)
• 29% fewer instances of unprotected sex in
group risk reduction intervention
Motivational Incentives/Contingency
Management
• Dr. Stitzer to review in detail this afternoon
• Effects consistently positive, sometimes
large, but strength often varies
• One example from non-CTN study
Treatment of Cocaine Dependence
Retained
Through
6 month Study
100
%
>8 Weeks of Cocaine
Abstinence
100
75
75
50
% 50
25
25
0
Incentive
Standard
0
Incentive
Standard
Higgins et al., 1994
Trials Where Study Intervention Did Not
Improve Outcomes of Usual Treatment
Riggs P, Winhusen T, Davies R, et al
J. Am. Acad. Child & Adolescent Psychiatry, 2011
• Randomized trial of OROS-MPH for adolescents seeking
treatment for substance use problems
• All patients received weekly CB therapy
• Surprising finding: Substance use and ADHD improved
equally in both groups
• Secondary outcome showed differential effect favoring
OROS-MPH for those with more severe ADHD
Impact of ADHD Treatment on Smoking
Cessation in ADHD Smokers
•
•
•
•
Winhusen T, Somoza E, Brigham G, et al
J. Clin. Psychiatry, 2010
256 smokers with ADHD randomized to OROS-MPH or
placebo
All received smoking cessation counseling and nicotine
patch
Smoking abstinence improved but did not differ between
groups
OROS-MPH improved ADHD
Motivational Interviewing to Improve Treatment
Outcome and Engagement in Persons Seeking
Treatment for Substance Abuse
Carroll K, Ball S, Nich C, et al
Drug & Alc Depend, 2006
• Randomized trial to usual treatment or
usual treatment + MI
• Everyone improved
• MI patients had better retention but no
differences in substance use
Motivational Enhancement Therapy to Improve
Treatment Utilization and Outcome in Pregnant
Substance Abusers
Winhusen T, Kropp F, Babcock D, et al
J. Subst. Abuse Treatment, 2008
• Randomized trial to usual treatment or
usual treatment + MET
• Everyone improved
• No differences between groups
• Some evidence of site differences and that
MET might be helpful for minority patients
12-Step Facilitation for Stimulant Users
Donovan D, Daley D, Brigham G, et al
J. Substance Abuse Treatment, 2012
• Used group sessions to facilitate participation in
12-Step programs
• Mixed findings
- Intervention increased odds of abstinence
- But, more days of use if were not abstinent
Brief Strategic Family Therapy vs. Usual
Treatment
Robbins M, Feaster D, Hoirigan V, et al
J. Consult. Clin. Psychology, 2011
• Randomized trial to usual treatment or
BSFT
• Overall improvement
• Median days of substance use less in
BSFT than TAU group at last observation
point but similar at other points
Implementing Rapid HIV Testing With or
Without Risk Reduction Counseling In Drug
Treatment Centers
•
•
•
•
•
Metsch L, Feaster D, Gooden L, et al
Am. J. Pub. Health, 2012
1281 patients who reported no HIV testing in last year
3 groups: off-site testing; on-site testing with risk
reduction counseling; verbal testing information only
On-site groups received more test results
No differences in HIV risk at 6 months
Though negative, an important finding due to cost
implications of requiring risk reduction counseling
What Can We Conclude?
• Methadone, Suboxone and ER naltrexone for opioid
addiction have consistently strong effects
• Motivational Incentives and Contingency Management
have consistently positive effects for a wide range of
addictions but can vary in magnitude of effect
– Widely used in methadone and Suboxone programs (i.e. urine
testing and reduced visits)
• Skills training in HIV sex risk reduction with women had
strong effect, but the magnitude of the effect was an
exception for psychosocial treatment approaches
Conclusions (continued)
• Having said that, usual counseling and 12-Step
treatments doing pretty well
• Finding equal outcomes with different kinds of
treatment consistent with:
– Luborsky paper from 1980’s showing different types
of psychotherapies produce approximately equal
outcomes of mild/moderate effect sizes
– Disappointing to investigators, but useful if the
therapy increases costs but does not add benefits
Implementation Problems
• Though opioid treatment medications highly
effective:
– Not always reimbursed
– Agonist treatment ideologically opposed
– Treatment duration sometimes limited
• Applying motivational incentives after NIDA
funding ends often a challenge
Back to Integration
• Suboxone and methadone studies, OROS-MPH study
show that:
- Psychosocial and medication therapies easily combined
- Can be delivered in primary care settings
- There should be no hurry to stop them
• Strong evidence that psychosocial and medication
treatments are effective with many patients
– Sustained remission and/or significant improvements occur
– “Cures” elusive
Back to Integration (cont.)
• Identifying untreated substance abuse problems
has potential to reduce medical costs via less
readmission, fewer co-morbidities
• Electronic medical records and cost data have
great potential to explore impact of:
- Identifying untreated substance use problems
- Applying patient-specific interventions
- Assessing outcomes
Patient Protection and
Affordable Care Act
• Likely to expand access to treatment for
problematic substance use
• Likely to provide more opportunities to
integrate screening and interventions for
problematic substance use and addiction
• Christiana an outstanding site to take
advantage of these opportunities