1. Psychosocial Combined with Agonist Maintenance Treatments versus Agonist Maintenance Treatments Alone for Treatment of Opioid Dependence (Review)
Amato, L., Minozzi, S., Davoli, M., Vecchi, S.,
Ferri, M., Mayet, S.
The Cochrane Collaboration

2. OBJECTIVES
To compare the effectiveness of the combination of psychosocial plus agonist maintenance interventions of any kind to any agonist maintenance treatments for opiate dependence, in: 1) retaining patients in treatment 2) reducing the use of substances 3) improving health and social status

3. Secondary Outcomes Compliance Craving
Psychiatric sxs/psychological distress
Quality of life
Severity of dependence
Death

4. Review Protocol Selection Criteria -
Randomised studies comparing any psychosocial plus any agonist with any agonist alone intervention for opiate dependence (1038 studies)
28 studies included, 46 excluded
2945 participants
66% male
average age 37
All but 2 studies in U.S.

5. Review Protocol Exclusion criteria 46 Inclusion criteria 28
Pregnant women
<18 years of age
type of intervention not in the inclusion criteria (22)
type of outcomes not in the inclusion criteria (8)
Type of participant (8)
study design not in the inclusion criteria
type of participants and type of intervention not in the inclusion criteria (1)
Inclusion criteria 28
RCTs
Adults over 18
Opiate addicts undergoing any psychosocial associated with any agonist maintenance intervention
Intervention – experimental (any psychosocial + agonist) compared to control (any agonist DRT)
Outcomes
retaining patients in treatment
reducing the use of substances
Improving health & social status

6. Review Protocol Key Words Databases, 1966 through 2008
Cochrane Drugs and Alcohol Group’s Register of Trials
Cochrane Central Register of Controlled Trials
MEDLINE
EMBASE
CINAHL
PyschInfo
Searches included non-English literature
Other strategies
Reference list of articles
Conference proceedings
Contacted investigators
Key Words
Substance related disorders
Opioid related disorders
Opiate related disorders
Psychosoical
Heroin
Narcotic
Randomized controlled trial
Contingency management
Community reinforcement
Psychotherapy
Methadone
Stress management
Case management
Etc…….

7. Data Collection & Analysis
Three reviewers
One searched hits by title & abstracts
Selected articles were read in full by two reviewers independently, assessing for inclusion criteria
Two reviewers independently extracted data
Discrepancies were resolved through discussion

9. Main Results
Abstinence at follow-up & continuous weeks of abstinence shows favor to the experimental group
No significant differences in all other outcomes:
Retention in tx
Reduction of opiate use during tx
Compliance
Psychiatric sxs/psychological distress
Depression
No differences between psychosocial interventions
Studies too short to assess mortality
Previous version of review showed reduction of opiate use during treatment in favor of experimental group

10. Data Collection & Analysis (Original, 2004; Revision, 2008)
Using Cochrane Handbook (2008) guidelines and updated version of RevMan, review was updated to include five new studies
Study quality high, with one moderate exception

11. Data Collection & Analysis Risk of Bias Figure 2
Data Collection & Analysis Risk of Bias Figure 2. Methodological quality graph: review authors’ judgments about each methodological quality item presented as percentages across all included studies (p. 10).

12. Data Synthesis
The outcomes from the individual trials have been combined through meta-analysis where possible (comparability of intervention and outcomes between trials) using a fixed effect model unless there was significant heterogeneity, in which case a random effect model was used. If all arms in a multi-arm trial are to be included in the metaanalysis participants of control group are considered twice in the statistical analysis.
Heterogeneity assessed using I2 , p< 0.05 for X2 test is significant for heterogeneity

13. Outcomes Relative effects (95% CI) No of Participants (studies
llustrative comparative risks* (95% CI)
_____________________________________
Assumed risk Corresponding risk
Control Any psychosocial +
any pharmacologic
Relative effects
(95% CI)
No of Participants
(studies
Quality of the evidence
(GRADE)
Retention in Tx
Medium risk population____________
737 per per 1000
(715 to 789)
RR 1.02
(0.97 to 1.07)
2193
(23)
⊕⊕⊕⊕
high
Use of primary substances
Medium risk population___________
440 per per 1000
(286 to 497)
RR 0.86
(0.65 to 1.13)
681
(8)
⊕⊕⊕
moderate1
# participants still in tx at end of follow-up
693 per per 1000
(534 to 735)
RR 0.91
(0.77 to 1.06)
289
(4)
# of participants abstinent at end of follow-up
429 per per 1000
(433 to 566)
RR 1.15
(1.01 to 1.32)
232
(5)
Compliance
The mean Compliance in the intervention group was 0.43 higher (0.05 lower to 0.92
higher)
685
(3)
moderate2
Psychiatric sxs
SCL-90
The mean Psychiatric symptoms SCL-90 in the intervention groups was 0.02 higher (0.19 lower to 0.23 higher)
323
Depression (BDI)
The mean Depression (BDI) in the intervention groups was 1.3 lower (3.31 lower to 0.72 higher)

14. Questions 12 different types of psychosocial interventions
Five Behavioral interventions (20): Acceptance and Commitment Therapy, Biofeedback, Cognitive-BehaviouralTherapy, Contingency Management Approaches, Information-Motivation-Behavioral Skills Model
Three psychoanalytic oriented interventions (4): Subliminal Stimulation, Supportive-Expressive Therapy, Shortterm Interpersonal Therapy
Two Counseling interventions (4): Customized Employment Support, Enhanced Methadone Services.
Other interventions (2): Relational Psychotherapies Mother’s Group, Twelve Step Facilitation Therapy (ITSF)

15. Questions
Most MMT programs include some type of psychosocial intervention, with a minimum of two, 20 minute sessions per month required by the feds
Three different types of drugs
Methadone
LAAM (1 study)
Buprenorphine (4 studies)
Methadone dosage
What about the effects of other drugs?
Study time 6 to 48 weeks
Heterogeneity, hmm…..?
Shouldn’t it be more tightly controlled?

16. Questions
For some outcomes reported in the included studies, it was impossible to make comparisons and pool results due the criteria adopted for reporting the results. Different rating instruments were used and for many of them the authors did not indicate the range of scores that were considered to represent mild, moderate and severe. This prevented comparison of results between studies. In addition, the results on urinalysis could not be summarized because these data were incongruous and the number of positive cases was unclear and possibly biased since the results are mainly based on number of positive tests rather than number of participants with positive tests.

17. Reference
Amato L, Minozzi S, Davoli M, Vecchi S, Ferri M, Mayet S. Psychosocial combined with agonist maintenance treatments versus agonist maintenance treatments alone for treatment of opioid dependence. Cochrane Database of Systematic Reviews 2008, Issue4. Art. No.: CD DOI: / CD pub3.