Use of slow-release oral morphine for the treatment of people with opioid dependence

Opioid dependence is associated with public health and social problems. People injecting opioids are particularly at risk, not only because they become dependent faster than with other routes of administration but also because they are exposed to consequences such as an increased risk of overdose mortality, infective diseases and health issues. At least three-quarters of global opiate users consume heroin.

Opioid substitution treatment involves prescribing an opioid to replace street heroin or other opioids. This is a long-term treatment that has been shown to reduce injecting of street heroin and the risk of death and blood-borne virus transmission, and to reduce involvement in crime.

Maintenance treatments that are effective in retaining people in treatment and suppressing heroin use include methadone, buprenorphine, and dyacethilmorphine, alone or combined with psychosocial treatments. In order to diversify the treatment possibilities, it is important to clarify the benefits that each specific intervention can bring to patients. Slow release oral morphine (SROM) is given once daily and has been proposed for people who cannot tolerate methadone or who respond poorly to other available maintenance treatments.

This review did not identify sufficient evidence to assess the effectiveness of SROM for opioid maintenance. Only three randomised controlled trials involving 195 participants met our inclusion criteria. The findings of 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 clearly different among the compared interventions. Adverse effects were more frequent with SROM than buprenorphine or methadone, including stomach cramps, headache, toothache, constipation, vomiting and insomnia.

These studies had small numbers of participants, very short follow -up and were designed to answer different questions. Overall, the quality of the evidence can be judged as low.

Authors' 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.

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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.

Objectives: 

To evaluate the efficacy of SROM as an alternative maintenance pharmacotherapy for the treatment of opioid dependence.

Search strategy: 

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.

Selection criteria: 

Randomised controlled trials (RCTs) and quasi-randomised trials assessing efficacy of SROM compared with other maintenance treatment or no treatment.

Data collection and analysis: 

Two review authors independently selected articles for inclusion, extracted data and assessed risk of bias of included studies.

Main 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.

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