Buprenorphine versus methadone in the treatment of pregnant opioid-dependent patients: effects on the neonatal abstinence syndrome. Comparison of methadone and slow-release morphine maintenance in pregnant addicts. Methadone versus buprenorphine in pregnant addicts: a double-blind, double-dummy comparison study.
This study was designed to compare the neonatal abstinence syndrome (NAS) in neonates of methadone and buprenorphine maintained pregnant opioid-dependent women and to provide preliminary safety and efficacy data for a larger multi-center trial. This randomized, double-blind, double-dummy, flexible dosing, parallel-group controlled trial was conducted in a comprehensive drug-treatment facility that included residential and ambulatory care. Participants were opioid-dependent pregnant women and their neonates. Treatment involved daily administration of either sublingual buprenorphine or oral methadone using flexible dosing of 4-24 mg or 20-100 mg, respectively. Primary a priori outcome measures were: (1) number of neonates treated for NAS; (2) amount of opioid agonist medication used to treat NAS; (3) length of neonatal hospitalization; and (4) peak NAS score. Two of 10 (20%) buprenorphine-exposed and 5 of 11 (45.5%) methadone-exposed neonates were treated for NAS (p=.23). Total amount of opioid-agonist medication administered to treat NAS in methadone-exposed neonates was three times greater than for buprenorphine-exposed neonates (93.1 versus 23.6; p=.13). Length of hospitalization was shorter for buprenorphine-exposed than for methadone-exposed neonates (p=.021). Peak NAS total scores did not significantly differ between groups (p=.25). Results suggest that buprenorphine is not inferior to methadone on outcome measures assessing NAS and maternal and neonatal safety when administered starting in the second trimester of pregnancy. To investigate whether the neonatal abstinence syndrome (NAS) is different in children born to women maintained on slow-release morphine, compared with those maintained on methadone, and to compare additional drug consumption in these groups of women.
                An open, randomized trial was conducted in an established clinic. Forty-eight pregnant women who presented to the clinic as opiate or polysubstance abusers were enrolled and maintained on either methadone (24 women) or slow-release morphine (24 women) up to and following delivery. The programme included psychosocial therapy and support for their opiate-addicted partners.
                Standard urinalysis methods were used to measure consumption of cocaine and benzodiazepines during pregnancy. Injection sites were monitored to indicate additional opiate use. NAS was measured according to Finnegan score and the amount of phenobarbiturates prescribed to alleviate the symptoms.
                No difference was found in the number of days that NAS was experienced by neonates born to methadone or morphine maintained mothers (mean = 16 and 21 days, respectively). All children were born healthy and no serious complications arose. Fewer benzodiazepines (p < 0.05) and fewer additional opiates (p < 0.05) were consumed by the morphine-maintained women compared with those who took methadone, but no difference was seen in cocaine consumption. Nicotine consumption was reduced significantly in both groups during pregnancy (p < 0.02).
                Both methadone and morphine are suitable maintenance agents for pregnant opiate addicts. Maintenance agents that result in a less prolonged NAS should be studied in further trials. To evaluate the efficacy and safety of methadone versus buprenorphine treatment in pregnant opioid-dependent women.
                Randomized, double-dummy, double-blind, flexible-dosing comparison study.
                Addiction Clinic at the Medical University of Vienna, Austria.
                Eighteen women were assigned randomly to receive either methadone (n = 9) or buprenorphine (n = 9) during weeks 24-29 of pregnancy. After dropouts, data were available from 14 cases (six in the methadone and eight in the buprenorphine group).
                Sublingual buprenorphine tablets (8-24 mg/day) or oral methadone solution (40-100 mg/day), with matched placebos.
                Mothers: retention in treatment, urine toxicology and nicotine use. Neonates: Routine birth data, neonatal abstinence syndrome (NAS) in severity and duration.
                There was somewhat greater retention in the buprenorphine group but significantly lowered use of additional opioids in the methadone group (P = 0.047).Neonates: There was earlier onset of NAS in neonates born to the methadone (mean 60 hours) than to the buprenorphine groups (mean 72 hours after last medication); 43% did not require NAS-treatment with short treatment duration in both groups (mean 5 days).
                This preliminary study had limited power to detect differences but the trends observed suggest this kind of research is practicable and that further studies are warranted.
We didn't find any significant difference between the drugs compared both for mother and for child outcomes; the trials retrieved were too few and the sample size too small to make firm conclusion about the superiority of one treatment over another. There is an urgent need of big randomised controlled trials.