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Minozzi S., Amato L., Bellisario C. et al.
Cochrane Database of Systematic Reviews: 2013, 12, Art. No.: CD006318.
Is it better to prescribe pregnant opioid-dependent women methadone, buprenorphine or oral morphine? Just four randomised trials have addressed this issue and their findings are inconclusive, suggesting greater holding power for methadone but less severe neonatal withdrawal with buprenorphine.
Summary Heroin crosses the placenta and pregnant, opiate-dependent women experience a six-fold increase in maternal obstetric complications such as low birth weight, toxaemia, third-trimester bleeding, malpresentation, puerperal morbidity, foetal distress and meconium aspiration. Neonatal complications include withdrawal, postnatal growth deficiency, microcephaly, neuro-behavioural problems, increased neonatal mortality and sudden infant death syndrome.
This review aimed to assess the effectiveness of maintenance treatments such as methadone maintenance for the treatment of pregnant women and the welfare of their babies.
Four trials were found which randomly allocated women to maintenance versus alternative procedures. Three compared methadone and buprenorphine.
Evidence was insufficient say which treatment is superior overall or to conclude they are equivalent.
However, while methadone seems superior at retaining patients in treatment, buprenorphine seems to lead to less severe neonatal abstinence syndromes.
Among women and babies facing these risks, this review aimed to assess the effectiveness of treatments for the expectant mother as methadone maintenance compared to no intervention, or compared to another pharmacological or psychosocial intervention. Impacts considered were child health, neonatal mortality, retaining pregnant women in treatment, and reducing their substance use. Studies had to have randomly allocated opiate-dependent pregnant women to a maintenance treatment versus an alternative procedure.
Four such trials were found involving 271 women. Two involved outpatients in Austria, one inpatients in the USA, and one was an international study conducted in Austria, Canada and the USA. In all the trials the alternative procedure was itself a different maintenance treatment. Three trials compared methadone with buprenorphine and one methadone with oral, slow-release morphine. All the included studies ended immediately after the baby was born.
Across the three trials which compared methadone with buprenorphine, retention was best when women had been offered methadone; the proportion of women who dropped out of treatment with methadone was about two-thirds that of women allocated to buprenorphine. Across the two studies which provided this data, there was no statistically significant difference in the proportions of women who continued to use their main problem drug, though the results favoured buprenorphine. Across the two studies whose data could be pooled, birth weight was higher in the buprenorphine group; the third study found no statistically significant difference. APGAR scores indicative of neonatal health did not significantly differ in the two studies to report this. Many measures were used in the studies to assess neonatal abstinence syndrome. The number of newborns treated for neonatal abstinence syndrome, the most critical outcome, did not differ significantly between babies born to mothers allocated to methadone versus buprenorphine. Only one study reported side effects; for the mothers there was no statistically significant difference but newborns in the buprenorphine group suffered significantly fewer serious side effects.
The single study to compare methadone with oral, slow-release morphine found no drop-out in either group. Mothers were over twice as likely to be abstinent from heroin if allocated to morphine. No side effects were reported for the mother, whereas one child in the methadone group had central apnoea (a temporary interruption in breathing) and one child in the morphine group had obstructive apnoea.
There were insufficient significant differences between methadone and buprenorphine or slow-release morphine to permit conclusions about which treatment is superior to another across all relevant outcomes. Even though a multi-centre, international trial with 175 pregnant women has recently been completed and included in this review, the body of evidence is still too small to permit the opposite conclusion – that the treatments are equivalent. However, while methadone seems superior in terms of retaining patients in treatment, buprenorphine seems to lead to less severe neonatal abstinence syndromes. No severe complications were noted.
The major flaw in the studies was that three out of four had a high drop-out rate (30% to 40%) and this differed between the women allocated to maintenance versus those allocated to alternative procedures.
Last revised 21 April 2015. First uploaded 16 April 2015
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STUDY 2019 Efficacy and cost-effectiveness of an adjunctive personalised psychosocial intervention in treatment-resistant maintenance opioid agonist therapy: a pragmatic, open-label, randomised controlled trial