毒理性
哺乳期使用概述：多塞平未获得美国食品药品监督管理局在美国的上市批准，但在其他国家可用。有限的信息表明，母亲每日剂量高达225毫克时，在乳汁和哺乳婴儿的血清中产生的水平较低，并且不会导致不良发育后果。多塞平预计不会对哺乳婴儿产生任何不良影响，特别是如果婴儿年龄超过2个月。
对哺乳婴儿的影响：八位因抑郁症接受多塞平治疗的妇女哺乳了她们的婴儿（具体程度未说明），婴儿年龄为0.13至12.5个月。母亲用药剂量为每日25至225毫克（每日0.38至4.5毫克/千克）。没有任何婴儿出现明显的不良反应。
一项回顾性病例对照研究对15位在哺乳期服用多塞平治疗抑郁症的母亲进行了调查，将她们的婴儿与一组15位未在哺乳期服用抗抑郁药的抑郁母亲以及另外36位没有抑郁症的母亲所生的婴儿的神经认知结果进行了比较。服用多塞平的母亲在哺乳期间每日剂量为150至225毫克，持续时间为4至134周。婴儿在哺乳期间通过母乳接触多塞平的时间为3至152周，并在3至5岁时进行了评估。没有证据表明对婴儿发育有负面影响，使用了许多评分量表。
两名婴儿在母亲使用多塞平期间哺乳了7至18周。两种药物都是在婴儿8周大时开始使用的。一位母亲开始时服用每日50毫克的剂量，后增加到每日100毫克；她在哺乳期间服用了33周的多塞平。另一位母亲每日服用225毫克，并在哺乳期间为她的婴儿哺乳了25周。正式测试表明，直到30个月大，婴儿的发育没有受到不良影响。
对泌乳和母乳的影响：一名服用多塞平的妇女报告出现乳汁分泌过多。
一项观察性研究调查了在怀孕前两年内服用抗抑郁药的2859位妇女的结果。与怀孕期间未服用抗抑郁药的妇女相比，整个孕期（三个季度）都服用抗抑郁药的妇女在出院时哺乳的可能性降低了37%。仅在第三季度服用抗抑郁药的妇女在出院时哺乳的可能性降低了75%。仅在第一季度和第二季度服用抗抑郁药的妇女在出院时哺乳的可能性没有降低。文中未具体说明母亲使用的抗抑郁药种类。
一项回顾性队列研究调查了2001年至2008年的医院电子医疗记录，比较了在晚期妊娠期间被开出抗抑郁药的妇女（n = 575）与患有精神疾病但未接受抗抑郁药的妇女（n = 1552）以及没有精神疾病诊断的妇女（n = 30,535）。服用抗抑郁药的妇女在出院时哺乳的可能性比没有精神疾病诊断的妇女低37%，但与未接受治疗的患有精神疾病的母亲相比，哺乳的可能性没有降低。这些母亲中没有人在服用多塞平。
在一项针对1999年至2008年的80,882对挪威母婴对的研究中，392位妇女报告了产后新开始使用抗抑郁药，201位报告她们从怀孕期间继续使用抗抑郁药。与未暴露的对照组相比，晚期妊娠使用抗抑郁药与哺乳开始的可能性降低7%有关，但对哺乳持续时间或专一性没有影响。与未暴露的对照组相比，新开始或重新开始使用抗抑郁药与在6个月时主要哺乳的可能性降低63%，任何哺乳的可能性降低51%，以及突然停止哺乳的风险增加2.6倍有关。具体抗抑郁药未提及。
◉ Summary of Use during Lactation:Dothiepin is not approved for marketing in the United States by the U.S. Food and Drug Administration, but is available in other countries. Limited information indicates that maternal doses of up to 225 mg daily produce low levels in milk and breastfed infants' serum, and cause no adverse developmental consequences. Dothiepin would not be expected to cause any adverse effects in breastfed infants, especially if the infant is older than 2 months.
◉ Effects in Breastfed Infants:Eight women who were receiving dothiepin for depression breastfed (extent not stated) their infants aged 0.13 to 12.5 months of age. Maternal dosages ranged from 25 to 225 mg daily (0.38 to 4.5 mg/kg daily). None of the infants had any noticeable adverse reactions.
A retrospective, case-control study of 15 women who breastfed while taking dothiepin for depression compared the neurocognitive outcomes of their infants to those in a group of 15 depressed mothers who had not taken an antidepressant during breastfeeding and another 36 women without depression. The mothers in the dothiepin group had taken dosages of 150 to 225 mg daily for 4 to 134 weeks during breastfeeding. Infants had been exposed to dothiepin in breast milk at times from 3 to 152 weeks of age and were assessed at 3 to 5 years of age. There was no evidence of negative effects on the infants' development using a number of rating scales.
Two infants were breastfed for 7 to 18 weeks during maternal use of dothiepin. The drug was started when both infants were 8 weeks of age. One mother started with a dose of 50 mg daily that was increased to 100 mg daily; she took dothiepin for 33 weeks during breastfeeding. The other mother was taking 225 mg daily and nursed her infant for 25 weeks during breastfeeding. Formal testing indicated no adverse effects on infant development up to 30 months of age.
◉ Effects on Lactation and Breastmilk:Galactorrhea has been reported in one woman taking dothiepin.
An observational study looked at outcomes of 2859 women who took an antidepressant during the 2 years prior to pregnancy. Compared to women who did not take an antidepressant during pregnancy, mothers who took an antidepressant during all 3 trimesters of pregnancy were 37% less likely to be breastfeeding upon hospital discharge. Mothers who took an antidepressant only during the third trimester were 75% less likely to be breastfeeding at discharge. Those who took an antidepressant only during the first and second trimesters did not have a reduced likelihood of breastfeeding at discharge. The antidepressants used by the mothers were not specified.
A retrospective cohort study of hospital electronic medical records from 2001 to 2008 compared women who had been dispensed an antidepressant during late gestation (n = 575) to those who had a psychiatric illness but did not receive an antidepressant (n = 1552) and mothers who did not have a psychiatric diagnosis (n = 30,535). Women who received an antidepressant were 37% less likely to be breastfeeding at discharge than women without a psychiatric diagnosis, but no less likely to be breastfeeding than untreated mothers with a psychiatric diagnosis. None of the mothers were taking dothiepin.
In a study of 80,882 Norwegian mother-infant pairs from 1999 to 2008, new postpartum antidepressant use was reported by 392 women and 201 reported that they continued antidepressants from pregnancy. Compared with the unexposed comparison group, late pregnancy antidepressant use was associated with a 7% reduced likelihood of breastfeeding initiation, but with no effect on breastfeeding duration or exclusivity. Compared with the unexposed comparison group, new or restarted antidepressant use was associated with a 63% reduced likelihood of predominant, and a 51% reduced likelihood of any breastfeeding at 6 months, as well as a 2.6-fold increased risk of abrupt breastfeeding discontinuation. Specific antidepressants were not mentioned.
来源:Drugs and Lactation Database (LactMed)
