Psychosocial Combined with Agonist Maintenance Treatments versus Agonist

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

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

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

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 37 • All but 2 studies in U. S.

Review Protocol • 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 • Exclusion criteria 46 – 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)

Review Protocol • Databases, 1966 through 2008 – Cochrane Drugs and Alcohol Group’s Register of Trials – Cochrane Central Register of Controlled Trials – MEDLINE – EMBASE – CINAHL – Pysch. Info – 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…….

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

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

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

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).

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 I 2 , p< 0. 05 for X 2 test is significant for heterogeneity

Outcomes Retention in Tx llustrative comparative risks* (95% CI) Relative effects ___________________ (95% CI) Assumed risk Corresponding risk Control Any psychosocial + any pharmacologic No of Participants (studies Quality of the evidence (GRADE) Medium risk population______ 737 per 1000 752 per 1000 (715 to 789) RR 1. 02 (0. 97 to 1. 07) 2193 (23) ⊕⊕⊕⊕ high Medium risk population______ 440 per 1000 378 per 1000 (286 to 497) # participants still in tx Medium risk population______ at end of follow-up 693 per 1000 631 per 1000 (534 to 735) Medium risk population______ # of participants 429 per 1000 493 per 1000 abstinent at end of (433 to 566) follow-up RR 0. 86 (0. 65 to 1. 13) 681 (8) ⊕⊕⊕ moderate 1 RR 0. 91 (0. 77 to 1. 06) 289 (4) ⊕⊕⊕⊕ high RR 1. 15 (1. 01 to 1. 32) 232 (5) Use of primary substances The mean Compliance in the intervention group was 0. 43 higher (0. 05 lower to 0. 92 higher) 685 (3) ⊕⊕⊕ moderate 2 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 (4) ⊕⊕⊕⊕ high Depression (BDI) The mean Depression (BDI) in the intervention groups was 1. 3 lower (3. 31 lower to 0. 72 higher) 323 (4) ⊕⊕⊕⊕ high Compliance

Questions • 12 different types of psychosocial interventions – Five Behavioral interventions (20): Acceptance and Commitment Therapy, Biofeedback, Cognitive. Behavioural. Therapy, 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)

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?

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.

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, Issue 4. Art. No. : CD 004147. DOI: 10. 1002/14651858. CD 004147. pub 3.