Posted by djmmm on July 26, 2003, at 20:47:28
In reply to pregnancy and antidepressants, posted by aimee fay on July 26, 2003, at 20:06:24
> has anyone stopped antidepressants to get pregnant. I'm currently trying to do both and would appreciate anyones advice or personal experiences both good and bad
> thanks aimeethis info may help you:
Researchers Assess Safety of Prenatal Exposure to SSRIs
from The Brown University Child and Adolescent Psychopharmacology Update
Posted 11/25/2002Introduction
Concern over the potential effects of neonatal exposure to SSRI antidepressants has risen over the past several years, especially after recent reports of a possible discontinuation syndrome in neonates exposed to paroxetine. A 1998 report noted that there were very limited data at that time on the safety of SSRIs in the human fetus. While more information has become available in the intervening years, concrete data on which to base practical recommendations remain scarce.The greatest quantity of data available are on the first SSRI to be introduced, fluoxetine. So far, studies have not found evidence of morphologic or functional teratogenicity with fluoxetine, including a recent controlled study that examined birth weight, preschool IQ, language development and behavior (Nulman et al. 1997, 2001).
Adding to data on fluoxetine, a 1998 report by Kulin et al. discussed a prospective, controlled trial conducted through nine Teratology Information Service centers in the U.S. and Canada. The trial compared 267 women exposed to the newer SSRIs (fluvoxamine, paroxetine or sertraline) during pregnancy to 267 control subjects exposed to nonteratogenic agents. The investigators concluded that there did not appear to be a significant increase in the risk of major congenital malformations with the newer SSRIs when used at recommended doses. They also found that pregnancy outcomes were not different between women who took an SSRI throughout pregnancy and those who took an SSRI only during the first trimester.
According to Lori L. Altshuler, M.D., of the UCLA Neuropsychiatric Insitute and the VA Greater Los Angeles Healthcare System, "Of all of the different classes of drugs, even though SSRIs are the newest, we have the most data on these. We know the most about fluoxetine, Prozac."
Altshuler explained that over 2,000 cases of pregnant women on fluoxetine have been reported to the Lilly (the manufacturers of fluoxetine) registry, and the data are promising. Data on the other SSRIs also look promising, she noted.
All of the SSRIs fall in category "C" of the FDA's drug use in pregnancy labeling system. A drug is classified "C" if animal studies have shown an adverse effect or have not been conducted and there are no adequate and well-controlled studies in pregnant women. While existing knowledge seems to indicate that the SSRIs are not associated with major teratogenicity, findings on minor malformations and perinatal complications are mixed.
Paroxetine Discontinuation
Motherisk, a program of the Division of Clinical Pharmacology & Toxicology at the Hospital for Sick Children and the University of Toronto has conducted a number of studies to assess the risk of SSRIs taken during pregnancy. A report from members of the group in 2001 (Stiksal et al.) detailed complications consistent with paroxetine withdrawal in four infants. The main symptoms presented included jitteriness, vomiting, irritability and hypoglycemia. Although the authors recommended close observation of neonates exposed to paroxetine in utero, the cause of this syndrome was not certain.Shinya Ito, M.D., head of the Division of Clinical Pharmacology & Toxicology at the Hospital for Sick Children and University of Toronto noted that it could not be ascertained from the first four cases they observed whether the symptoms might possibly be due to discontinuation, toxicity or other factors. However, based on the cases they've seen to date, Ito noted that it may be a discontinuation syndrome that they have observed. "Maybe the receptor site in the brain gets used to the drug level, so even a slight decrease makes a difference," Ito told The Brown University Child and Adolescent Psychopharmacology Update.
In order to better understand the effects of prenatal paroxetine exposure, researchers associated with the Motherisk program began a prospective, controlled study examining perinatal outcomes in babies exposed to paroxetine in the third trimester and healthy controls. Preliminary results of this study were presented at the 2002 Pediatric Academic Societies (PAS) meeting (Costei 2002); more complete results will be published in a major journal this month.
The study assessed 55 pregnant women exposed to paroxetine during the third trimester, 27 women using paroxetine during the first or second trimester and 27 women using other, non-teratogenic drugs. These subjects were matched for maternal age, gravity, parity, social drug use and nonteratogenic drug use. Subjects who discontinued paroxetine before the third trimester or who received other drugs known to cause withdrawaltype symptoms (opioids, benzodiazepines, etc.) were excluded.
The investigators found that 12 of the neonates exposed to paroxetine during the third trimester experienced complications necessitating intensive management and prolonged hospitalization, while only three in the comparison group experienced such complications (p<0.03). Nine of the neonates exposed to paroxetine in late pregnancy experienced respiratory distress followed by hypoglycemia and jaundice. These signs disappeared within one or two weeks. Also, 20 percent of the infants in the study group were born preterm, compared to only 3.7 percent in the comparison group (p=0.02). The researcher's initial report did not discuss whether the increased rate of respiratory distress might be assoicated with the increased rate of prematurity.
Clinical Picture
"The main feature we observed was difficulty in breathing. Some required observation, others required intervention -- intubation," Ito said. However, no structural damage to tissues or organs or similar sequelae were found in the infants.It is difficult to compare discontinuation in adults and neonates for a variety of reasons, Ito notes, including the inability of neonates to report psychological symptoms.
The Motherisk program is now prospectively following a number of infants in order to better determine the percentage of neonates experiencing this possible syndrome among those exposed to paroxetine. Over 50 cases have been assessed so far, and the investigators are aiming to look at 100 subjects before drawing any conclusions.
"We don't recommend [discontinuing] antidepressants during pregnancy," Ito notes. However, if the researchers find a high rate of discontinuation symptoms associated with paroxetine, it may be advisable in the future to recommend another antidepressant to pregnant women.
"We are trying to confirm whether the higher rate is reproducible, not just a bump in the statistics," noted Ito. "One thing we don't want to do is scare the public."
The possible incidence of a neonatal discontinuation syndrome with paroxetine cannot simply be due to the short half-life of paroxetine, according to Ito. Other SSRIs with shorter or similar half-lives have not been as frequently implicated, but this may be due to a reporting bias because of the high usage and profile of paroxetine. According to Ito, 7 of 10 women taking SSRIs and seen through the Motherisk program are taking paroxetine. Additionally, sufficient data to compare the effects of prenatal exposure to different SSRIs has not yet been collected, according to Ito.
Treatment Considerations
Furthermore, there is not enough data to make practical recommendations for avoiding the discontinuation syndrome in infants -- short of stopping antidepressant treatment. However, both Altshuler and Ito warned of the consequences for pregnant women of inadequate treatment of depression. In fact, while Nulman et al. (2002) did not find fluoxetine treatment to be associated with negative outcomes in child development, they did find maternal level of depression to be negatively associated with measures of child development.Data necessary to make other practical recommendations for administering SSRIs during pregnancy are also limited.
"No one can say 'This is how to take [an infant] off a drug if exposed prenatally,'" Altshuler said.
Altshuler also notes that while stopping antidepressant treatment during or following pregnancy is not advisable in most cases, given the little that is known about discontinuation, some women choose not to breastfeed their infants if they do continue taking SSRIs.
"About 50 percent of the women I've treated who've continued antidepressant treatment have chosen not to breastfeed and to bottlefeed instead," Altshuler noted. However, while all the antidepressants get into breastmilk, according to Altshuler, very little seems to get into infants' bloodstream via breastfeeding
poster:djmmm
thread:245669
URL: http://www.dr-bob.org/babble/20030723/msgs/245684.html