number of babies born hooked on their mothersí opioids has
been soaring for almost two decades, yet experts still are not
sure whether morphine or methadone is best to gradually break
the infantsí drug dependence.
rigorous new government-funded study has found that methadone
has a slight advantage over morphine, modestly reducing babiesí
length of treatment and hospitalization.
study, published recently in JAMA Pediatrics, further
complicates the question of how to safely and effectively
treat babies going through withdrawal, called neonatal
abstinence syndrome (NAS). At the behest of the U.S. Food and
Drug Administration, the researchers spent a year developing a
methadone formulation that could be custom-prepared at each of
the eight participating hospitals. This was done to avoid
using commercial methadone solutions, which are not approved
for pediatric use and contain alcohol as a preservative.
can say whether the alcohol is harmful for newborns, but the
researchers and the FDA wanted to eliminate the theoretical
commercial methadone solutions, 15 percent is alcohol,"
said lead researcher Jonathan M. Davis, a Tufts Medical Center
pediatrician who chairs the FDAís neonatal advisory
committee. "Thatís double the amount of alcohol in a
glass of wine. Most people I tell about this, theyíre
dumbfounded, partly because no one looks at the label."
said he hoped the results prompt a pharmaceutical company to
seek FDA approval of an alcohol-free pediatric methadone
percent of hospitals treat newborn withdrawal with morphine,
the only opioid approved for pediatric use. Like adults in
withdrawal, infants feel the effects in every organ system;
their symptoms include tremors, muscle spasms, shrill crying,
irritability, diarrhea, vomiting, poor sleeping, and seizures.
and another medication, buprenorphine, are milder opioids used
to help people stop using painkillers or illicit opiates such
as heroin. Even pregnant women are put on methadone or
buprenorphine to cut cravings without delivering euphoric
effects because abruptly quitting opioids increases the risk
of miscarriage. However, their newborns may suffer withdrawal.
which is not approved for babies, has not caught on for NAS
treatment, even though Thomas Jefferson University researchers
published a study a year ago that found it reduced hospital
stays compared to morphine. Jefferson now relies on
buprenorphine to treat NAS.
Kraft, the physician and clinical pharmacologist who led the
Jefferson study, said the buprenorphine formulation contains
30 percent alcohol.
did measure the levels (of blood alcohol) in the babies,"
Kraft said recently. "It turns out infants clear it
quickly, quicker than adults. But in terms of the safety of
alcohol in neonates, itís not well-established."
who was part of a group that monitored the safety of the new
study, called the results "exciting."
believe, although it hasnít been demonstrated, that the
results would be comparable with commercial methadone"
solutions, he said.
study ó the largest of its kind and funded by the National
Institute on Drug Abuse ó involved 116 infants who were
randomly assigned to methadone or morphine. Their doses were
based on their weight and the severity of their withdrawal
symptoms. Medical staff did not know which drug the babies
babies on methadone needed treatment for an average of about
14 days during an average hospital stay of 22 days. On
morphine, babies averaged about 16 days of treatment and 23
days in the hospital.
advantage of methadone: Itís longer-acting, so the babies
needed only three doses a day, compared to six doses of
morphine. (The methadone regimen included three placebo doses
so it was indistinguishable from morphine.)
study, like the Jefferson study, did not consider costs. But
reducing hospitalization by even a day or two could translate
to big health-care savings. A recent study calculated hospital
care costs $1.5 billion for the estimated 23,000 infants a
year who go through withdrawal.
count is rising. In Pennsylvania, for example, the number of
drug-exposed newborns has skyrocketed from 788 in 2000 to
3,289 last year; about 60 percent suffered from NAS, according
to an analysis by the Pennsylvania Health Care Cost
study suggests methadone is a more effective agent,"
Davis said. "And three times a day is a better approach
than six times a day. Thereís less chance for error. But Iíd
love to see a safer formulation."