Drug utilization in breast-feeding women. A survey in Oslo

Summary In a retrospective questionnaire survey of 885 women who had given birth 3–5 months before, fewer of those who were still breast-feeding at 4 months (n=645) were using drugs than those who had stopped breast-feeding before 4 months (n=240), during the 2 week period preceding registration. The average number of doses (Defined Daily Doses/1000 women/day) was 166 and 307, respectively, in that period. The number of doses taken was significantly associated with the use of oral contraceptive agents (p<0.005) and young maternal age (p<0.05). Most of the variation in drug use between breast-feeding and not breast-feeding mothers was probably due to the greater use of contraception by the latter. The number of drugs used per mother in the 4 month period seemed to be best predicted by her and her infant's disorders. Long-term medication in breast-feeding women included many drugs for which there is incomplete or no data about milk transfer, e.g. salbutamol, clemastine, dexchlorpheniramine, phenylpropanolamine, cromoglycate and levomepromazine. The disorders most extensively treated with drugs in this period were dyspepsia, haemorrhoids and inflammation of the breast. The finding that smoking was associated with early weaning and consumption of alcohol with prolonged breast-feeding calls for further investigation. More information on these drug and health issues to the breast-feeding mother is highly desirable.     

The use of selective serotonin reuptake inhibitors during pregnancy and breast-feeding: a review and clinical aspects

Mood and anxiety disorders are common in women during their childbearing years. The prevalence of depression has been reported to be between 10% and 16% during pregnancy. The use of selective serotonin reuptake inhibitors during pregnancy or lactation is, to date, not promoted because of lack of safety documentation. However, the off-label use of these drugs has been common for several years. In the treatment of mood and anxiety disorders during pregnancy, the serotonin reuptake inhibitors are often preferred over tricyclic antidepressants because of their relatively few adverse effects and safety in overdose. This has created concern among women planning pregnancies and pregnant women, as well as among their families and physicians. Several studies and reports of the use of serotonin reuptake inhibitors during both pregnancy and lactation have been published and advanced our knowledge. We here review and discuss those studies which have been published so far on this subject.     

哺乳期使用选择性5羟色胺再摄取抑制剂类抗抑郁药的安全性

抑郁症是哺乳期常见的疾病之一,目前关于哺乳期使用选择性5羟色胺再摄取抑制剂(SSRI)类抗抑郁药的安全性尚缺乏足够的证据。本文就哺乳期常用的SSRI类抗抑郁药安全性研究作一综述,并给出建议。     

Stereoselective disposition of fluoxetine and norfluoxetine during pregnancy and breast-feeding

AIMS: To compare the disposition of fluoxetine and norfluoxetine enantiomers in the mother, foetus and infant. METHODS: Blood from pregnant women taking fluoxetine (n = 9), during pregnancy was sampled in the third trimester and at delivery (maternal and cord venous blood), and from the infants 48 h after delivery. The subset of these women who were breastfeeding, plus additional subjects recruited in the postpartum period, were studied further, and maternal and infant blood, and breast milk was sampled between 6 days and 11 months (n = 23). Drug and metabolite concentrations were measured using gas chromatography/mass spectrometry or liquid chromatography, tandem mass spectrometry. RESULTS: There was a high correlation between maternal and foetal (cord blood) fluoxetine and norfluoxetine enantiomers (r(2)-0.9), the mean foetal/maternal ratios (95% confidence intervals) being 0.91 (0.61, 1.02) and 1.04 (0.93, 1.05), for fluoxetine and norfluoxetine, respectively. In 2 day old infants exposed to the drug in utero, the fluoxetine and norfluoxetine plasma concentrations were the same as in cord blood at delivery. Over the next 2 months, the plasma concentrations in the infants fell progressively. Stereoselective disposition of both the drug and metabolite in the mother, foetus, infant and breast milk was observed. The S : R ratios in the foetus and newborn ( approximately 3) were significantly higher than in the serum ( approximately 2) or breast milk ( approximately 1.9) of the mothers, resulting in greater exposure of the foetus and infants to the biologically active enantiomers, particularly S-norfluoxetine. CONCLUSIONS: Foetal and infant exposure to fluoxetine and norfluoxetine is enhanced by their stereoselective disposition in the mother, foetus, breast milk and infant. Increased exposure may also result from decreased metabolism of the drug in the foetus and neonate.     

Drug use patterns and behaviours of young people at an increased risk of drug use during adolescence

The drug use patterns and behaviours of 90 young people who reported cannabis use from the age of 11/12 years when they entered post primary schooling and continued to report its use during three further annual data waves of the Belfast Youth Development Study (a longitudinal study of the onset and development of adolescent drug use) until the age of 15 are examined in this paper. The data collected from these young people revealed high levels of both licit and illicit drug use compared with young people who have not used cannabis by the age of 15. The findings suggest the existence of a ‘hidden’ high risk group of young people who continue to attend school regularly. This raises the question about the extent to which their needs are being met by existing school based drugs education and prevention initiatives which are often delivered through a standardised strategy for all school aged young people.     

Drugs and breast-feeding

(1) Report of severe adverse effects in infants from drugs passing into breast milk are rare. (2) Two reports of neurological disorders in infants due to doxepin, a tricyclic antidepressant, necessitating hospitalisation, serve as a reminder that this risk exists. (3) Epidemiological data are almost non existent. A prospective follow-up study of more than 800 breast-fed infants whose mothers were taking medicinal drugs showed minor adverse effects in 11% of the children (mainly diarrhoea, drowsiness and irritability). None of the mothers sought medical advice. (4) When a breast-feeding mother requires drug therapy, all available information should be weighed up before advising her to switch to bottle feeding.