title: Slow-release oral morphine as maintenance therapy for opioid dependence.
abstract: BACKGROUND
  Opioid substitution treatments are effective in retaining people in treatment and suppressing heroin use. An open question remains whether slow-release oral morphine (SROM) could represent a possible alternative for opioid-dependent people who respond poorly to other available maintenance treatments.
  
  
  OBJECTIVE
  To evaluate the efficacy of SROM as an alternative maintenance pharmacotherapy for the treatment of opioid dependence.
  
  
  METHODS
  We searched Cochrane Drugs and Alcohol Group's Register of Trials, Cochrane Central Register of Controlled Trials (CENTRAL - The Cochrane Library Issue 3, 2013), MEDLINE (January 1966 to April 2013), EMBASE (January 1980 to April 2013) and reference lists of articles.
  
  
  METHODS
  Randomised controlled trials (RCTs) and quasi-randomised trials assessing efficacy of SROM compared with other maintenance treatment or no treatment.
  
  
  METHODS
  Two review authors independently selected articles for inclusion, extracted data and assessed risk of bias of included studies.
  
  
  RESULTS
  Three studies with 195 participants were included in the review. Two were cross-over trials and one was a parallel group RCT. The retention in treatment appeared superior to 80% in all the three studies (without significant difference with controls). Nevertheless, it has to be underlined that the studies had different durations. One lasted six months, and the other two lasted six and seven weeks. The use of opioids during SROM provision varied from lower to non-statistically or clinically different from comparison interventions, whereas there were no differences as far as the use of other substances was concerned.SROM seemed to be equal to comparison interventions for severity of dependence, or mental health/social functioning, but there was a trend for less severe opiate withdrawal symptoms in comparison with methadone (withdrawal score 2.2 vs. 4.8, P value = 0.06). Morphine was generally well tolerated and was preferred by a proportion of participants (seven of nine people in one study). Morphine appeared to reduce cravings, depressive symptoms (measured using the Beck Depression Inventory; P value < 0.001), physical complaints (measured using the Beschwerde-Liste (BL); P value < 0.001) and anxiety symptoms (P value = 0.008). Quality of life in people treated with SROM resulted in no significant difference or a worst outcome than in those taking methadone and buprenorphine. Other social functioning measures, such as finances, family and overall satisfaction, scored better in people maintained with the comparison substances than in those maintained with SROM. In particular, people taking methadone showed more favourable values for leisure time (5.4 vs. 3.7, P value < 0.001), housing (6.1 vs. 4.7, P value < 0.023), partnerships (5.7 vs. 4.2, P value = 0.034), friend and acquaintances (5.6 vs. 4.4, P value = 0.003), mental health (5.0 vs. 3.4, P value = 0.002) and self esteem (8.2 vs. 5.7, P value = 0.002) compared to people taking SROM; while people taking buprenorphine obtained better scores for physical health.Medical adverse events were consistently higher in people in SROM than in the comparison groups. None of the studies included people with a documented poor response to other maintenance treatment.
  
  
  CONCLUSIONS
  The present review did not identify sufficient evidence to assess the effectiveness of SROM for opioid maintenance because only three studies meeting our inclusion criteria have been identified. Two studies suggested a possible reduction of opioid use in people taking SROM. In another study, the use of SROM was associated with fewer depressive symptoms. Retention in treatment was not significantly different among compared interventions while the adverse effects were more frequent with the people given SROM.
authors.affiliation: Interventions, Best Practice and Scientific Partners, European Monitoring Centre for Drugs and Drug Addiction, Lisbon, Portugal. marica.ferri@emcdda.europa.eu.
authors.forename: Marica
authors.initials: M
authors.lastname: Ferri
authors.forename: Silvia
authors.initials: S
authors.lastname: Minozzi
authors.forename: Alessandra
authors.initials: A
authors.lastname: Bo
authors.forename: Laura
authors.initials: L
authors.lastname: Amato
mesh_terms: D000284:Administration, Oral; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D009020:Morphine / Q000008:administration & dosage* / Q000009:adverse effects; D009294:Narcotics / Q000008:administration & dosage* / Q000009:adverse effects; D058850:Opiate Substitution Treatment / Q000009:adverse effects / Q000379:methods*; D009293:Opioid-Related Disorders / Q000188:drug therapy*; D011788:Quality of Life; D016032:Randomized Controlled Trials as Topic
chemical_list: D003692:Delayed-Action Preparations; D009294:Narcotics; D009020:Morphine