Pharmacological therapies for maintenance treatments of opium dependence

Opium is obtained from the unripe seed capsules of the poppy plant. Opium is usually used by smoking or by swallowing to create a feeling of euphoria, to provide pleasure or as an analgesic or hypnotic. Cultural attitudes affect the patterns of opioid use among different countries. In the Middle East and south east Asia, opium is used in many cases in social settings and the users do not suffer from considerable social dysfunction. It is used occasionally and mainly in male gatherings but regular use can cause dependence. Opium users have a more stable life style than heroin users and, of those who come for treatment, a higher proportion are married and live with their family.

Stopping opium use gives rise to a mild intensity opiate withdrawal syndrome. The physical signs of withdrawal syndrome usually stop after 14 days; but a protracted syndrome that includes reduced well-being, malaise and periodic strong cravings can continue for months. Completion of withdrawal and remaining abstinent is difficult and opium dependents often relapse if treatment does not continue after completion of withdrawal.

When the type of opioid used is less harmful than heroin, as with opium, there is a question as to what type of treatment or maintenance is most effective; detoxification from opium is short-lasting and better tolerated than detoxification from methadone.

Three randomised controlled trials involving 870 opium dependents were included in the review. In two of the trials different doses of the semi-synthetic opioid buprenorphine were compared. The higher doses of buprenorphine (4 mg/day and 8 mg/day, respectively) increased the probability of retention in treatment. The studies had a high risk of bias. In the third trial baclofen (an agonist of GABA-B receptors) was compared with placebo for maintenance treatment after a process of detoxification. Only 27 of the 40 participants were opium dependent and there was a trend for increased retention in treatment. Important outcomes such as drug use and drug side effects were not assessed.

Overall, the results from three trials are not sufficient to form a view on the effectiveness of any pharmacological intervention for opium dependence. Buprenorphine has partial agonist opioid activity and appears to be well-tolerated with minor side effects. However, buprenorphine abuse has emerged and been recognised as a problem in many Asian countries in the last two decades. Its use by injection is also quite common.

Authors' conclusions: 

It is not possible to conclude about the use of any kind of pharmacologic therapies for maintenance treatment of opium dependence.

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Background: 

Pharmacologic therapies for maintenance treatment of heroin dependence have been used and studied widely. Systematic reviews have demonstrated the effectiveness of such therapies. Opium dependence is associated with less problems and impairments and is less likely to be used by injecting, with consequent reductions in risk of overdose and blood-borne diseases. Although it is a common substance use disorder in many countries, a systematic review of the literature is lacking on the maintenance treatment for opium dependence.

Objectives: 

To evaluate the effectiveness and safety of various pharmacological therapies on maintenance of opium dependence (alone or in combination with psychosocial interventions) compared to no intervention, detoxification, different doses of the same intervention, other pharmacologic interventions and any psychosocial interventions.

Search strategy: 

We searched the following sources up to February 2012: Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, CINAHL, PsycINFO, regional databases (IMEMR and ASCI), national databases (Iranmedex and Iranpsych), main electronic sources of ongoing trials and reference lists of all relevant papers. Also, we contacted known investigators from some Asian countries to obtain details about unpublished trials.

Selection criteria: 

Randomised controlled clinical trials (RCTs) comparing any maintenance pharmacologic intervention versus no intervention, other pharmacologic or non-pharmacologic intervention for opium dependence.

Data collection and analysis: 

Two reviewers assessed the risks of biases and extracted data, independently.

Main results: 

Three RCTs recruiting 870 opium dependents were included. The studies made different comparisons so it was not possible to pool data. Only retention rate was assessed by the studies. Two studies compared different doses of buprenorphine: in one study, 4 mg/day of buprenorphine was compared with doses of 2 mg/day and 1 mg/day and in another study, 8 mg/day of buprenorphine was compared with doses of 3 mg/day and 1 mg/day. Comparisons showed a statistically significant difference between groups; higher doses of buprenorphine increased the probability of retention in treatment. The studies had high risks of biases. In the third study, after a process of detoxification, baclofen (60 mg/day) was compared with placebo for maintenance treatment. The difference in retention rate between groups was high, but it was not statistically significant.

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