毒理性
◉ 哺乳期使用概述：关于哺乳期间使用度洛西汀的已发表信息很少；然而，乳汁中的剂量很低，两名哺乳婴儿的血清水平也较低。如果母亲需要使用度洛西汀，这不是停止哺乳的理由。专家意见认为哺乳期间可以使用度洛西汀，并且一个安全评分系统发现谨慎地在哺乳期间使用度洛西汀是可能的。可能更倾向于使用已经更好研究过的替代药物，特别是在哺乳新生儿或早产儿时。监测婴儿是否困倦和喂养充足、体重增长以及发育里程碑，尤其是在较年轻、完全母乳喂养的婴儿中，以及在使用多种精神药物组合时。有报道称女性服用度洛西汀时出现了乳汁分泌过多。
◉ 对哺乳婴儿的影响：一位部分哺乳的母亲正在服用度洛西汀90毫克和缓释哌甲酯（Concerta）36毫克，用于治疗ADHD、广泛性焦虑症、边缘型人格障碍和抑郁症。她部分哺乳（具体量未说明）她的婴儿大约1个月。在6个月大时，婴儿的发展被认为是正常的，除了由先天性肺气道畸形引起的复发性肺炎。另一位母亲在部分哺乳（具体量未说明）期间每天服用度洛西汀60毫克。在6周大时，暴露的婴儿没有观察到不良事件。
◉ 对泌乳和母乳的影响：在一项小型的前瞻性研究中，8位正在服用一种选择性5-羟色胺再摄取抑制剂（SRI；其中3位服用氟西汀，每位服用西酞普兰、度洛西汀、艾司西酞普兰、帕罗西汀或舍曲林）的一胎母亲与423位没有服用SRI的母亲进行了比较。服用SRI的母亲在乳汁分泌激活（泌乳II期）的开始时间平均比对照组延迟了16.7小时（服用SRI的母亲在产后85.8小时，未服药的母亲在产后69.1小时），这使得延迟喂养行为的风险增加了两倍。然而，泌乳II期的延迟可能没有临床重要性，因为两组在产后4天以上经历喂养困难的比例没有统计学上的显著差异。
一位非孕妇女开始服用度洛西汀后，她的血清催乳素升高，之前服用文拉法辛后减少的乳汁分泌过多又增加了。停止度洛西汀后，她的催乳素降至正常，乳汁分泌过多停止。
一位正在服用度洛西汀（剂量未说明）治疗抑郁症的妇女报告乳头有乳白色分泌物。她以前使用抗抑郁药治疗时没有经历过这种效果。她的血清催乳素升高，头部MRI未发现肿瘤。停止度洛西汀后，她接受了艾司西酞普兰20毫克/日和卡贝缩酮0.5毫克每周两次治疗一个月。此时她的血清催乳素正常，乳汁分泌过多停止。
在一项研究中，法国药物警戒中心报告的催乳素血症及其症状（如男性乳房发育）病例中，未发现度洛西汀与其他药物相比有增加催乳素血症风险。
一位每天服用度洛西汀60毫克治疗抑郁症的妇女在服用该药总共10周后抱怨有乳白色乳汁分泌、乳房胀满和乳房疼痛。停止度洛西汀后改用安非他酮。停止度洛西汀两周后，乳汁分泌过多有所改善。停止度洛西汀六周后，她的血清催乳素从之前的37.9 mcg/L降至20.2 mcg/L。她的乳汁分泌过多可能是由度洛西汀引起的。
一位用度洛西汀30毫克/日治疗偏头痛的妇女在治疗的第十周开始出现双侧乳汁分泌过多。当时和随后的多次测量中，她的血清催乳素水平都在正常范围内。停用度洛西汀3天后，乳汁分泌过多停止。作者发现她的乳汁分泌过多可能是由度洛西汀引起的。
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，怀孕期间所有三个孕期都服用抗抑郁药的妇女在出院时哺乳的可能性降低了37%。仅在第三孕期服用抗抑郁药的妇女在出院时哺乳的可能性降低了75%。仅在第一和第二孕期服用抗抑郁药的妇女在出院时哺乳的可能性没有降低。研究中未说明母亲使用的抗抑郁药种类。
一项回顾性队列研究比较了2001年至2008年的医院电子医疗记录中在晚期妊娠期被分发抗抑郁药的女性（n = 575）与患有精神疾病但未接受抗抑郁药的女性（n = 1552）以及没有精神疾病诊断的母亲（n = 30,535）。与没有精神疾病诊断的妇女相比，接受抗抑郁药治疗的妇女在出院时哺乳的可能性降低了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。其中没有母亲服用度洛西
◉ Summary of Use during Lactation:Little published information is available on the use of duloxetine during breastfeeding; however, the dose in milk is low and serum levels were low in two breastfed infants. If duloxetine is required by the mother, it is not a reason to discontinue breastfeeding. Expert opinion finds duloxetine acceptable to use during breastfeeding, and a safety scoring system finds duloxetine use to be possible to use cautiously during breastfeeding. An alternate drug that has been better studied may be preferred, especially while nursing a newborn or preterm infant. Monitor the infant for drowsiness and adequate feeding, weight gain and developmental milestones, especially in younger, exclusively breastfed infants and when using combinations of psychotropic drugs. Galactorrhea has been reported in women taking duloxetine.
◉ Effects in Breastfed Infants:A partially nursing mother was taking duloxetine 90 mg and extended-release methylphenidate (Concerta) 36 mg daily for ADHD, generalized anxiety disorder, borderline personality disorder, and depression. She partially (amount not stated) breastfed her infant for about 1 month. At 6 months of age, infant's development was considered to be normal, except for recurrent pneumonia caused by congenital pulmonary airway malformation. Another mother took duloxetine 60 mg daily while partially (amount not stated) nursing her infant. At 6 weeks of age, no adverse events were observed in the exposed infant.
◉ Effects on Lactation and Breastmilk:In a small prospective study, 8 primiparous women who were taking a serotonin reuptake inhibitor (SRI; 3 taking fluoxetine and 1 each taking citalopram, duloxetine, escitalopram, paroxetine or sertraline) were compared to 423 mothers who were not taking an SRI. Mothers taking an SRI had an onset of milk secretory activation (lactogenesis II) that was delayed by an average of 16.7 hours compared to controls (85.8 hours postpartum in the SRI-treated mothers and 69.1 h in the untreated mothers), which doubled the risk of delayed feeding behavior compared to the untreated group. However, the delay in lactogenesis II may not be clinically important, since there was no statistically significant difference between the groups in the percentage of mothers experiencing feeding difficulties after day 4 postpartum.
After one nonpregnant woman began taking duloxetine, her serum prolactin increased and previous galactorrhea, which had decreased after stopping venlafaxine, increased again. After stopping duloxetine, her prolactin decreased to normal and galactorrhea ceased.
A woman who was taking duloxetine at an unspecified dose for depression reported a milky discharge from her nipples. She had not experienced this effect with previous antidepressant therapy. Her serum prolactin was elevated, and an MRI of her head found no tumors. Duloxetine was stopped and she was treated with escitalopram 20 mg daily and cabergoline 0.5 mg twice weekly for one month. At this time her serum prolactin was normal and the galactorrhea had stopped.
In a study of cases of hyperprolactinemia and its symptoms (e.g., gynecomastia) reported to a French pharmacovigilance center, duloxetine was not found to have an increased risk of causing hyperprolactinemia compared to other drugs.
A woman taking duloxetine 60 mg daily for depression complained of a milky breast discharge, breast fullness, and breast pain, after taking the drug for a total of 10 weeks. Duloxetine was discontinued and bupropion was started. Two weeks after stopping duloxetine, galactorrhea improved. Six weeks after stopping duloxetine, her serum prolactin had dropped from the previous level of 37.9 mcg/L to 20.2 mcg/L. Her galactorrhea was probably caused by duloxetine.
A woman being treated for migraine with duloxetine 30 mg daily began to have bilateral galactorrhea during the tenth week of treatment. At that time and on repeated measurements, her serum prolactin level was within the normal range. Her galactorrhea ceased 3 days after discontinuation of duloxetine. The authors found that her galactorrhea was probably caused by duloxetine.
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 duloxetine.
A woman with major depressive disorder received duloxetine 40 mg twice daily. After 2 weeks, she developed menstrual irregularities and a milky discharge from her breasts. Her serum prolactin was elevated at 205 mcg/L. The duloxetine dosage was decreased to 60 mg once daily and aripiprazole was begun at 2.5 mg daily and then increased to 5 mg daily. Within 2 weeks, galactorrhea had stopped and the serum prolactin had decreased to 118 mcg/L. Six weeks later, serum prolactin was 39 mcg/L. The combination was continued for another 39 weeks with no return of galactorrhea.
A 16-year-old girl was admitted for depression and suicide attempts. She had previously experienced galactorrhea while taking risperidone and escitalopram. She was started on duloxetine 20 mg daily which was increased to 40 mg daily after 5 days. Two days later, small amounts of milk appeared from the right breast. Her serum prolactin was mildly elevated at 26 mcg/L. The dose was reduced to 20 mg daily and the milk production ceased.
A woman with depression was treated with duloxetine 30 mg daily for 1 month, then 60 mg daily. After 4 months of therapy she presented with amenorrhea, lactation and hyperprolactinemia. The patient was treated with cabergoline 0.5 mg twice weekly and duloxetine was discontinued. One month later, the serum prolactin level was normal.
A woman with multiple sclerosis had been treated with duloxetine 60 mg daily for pain and depression for 3 months. She noted a milk-like breast discharge for a month and her serum prolactin was elevated. Duloxetine was changed to escitalopram 10 mg daily. Within days, her galactorrhea stopped and her serum prolactin decreased. Cabergoline 0.25 mg twice weekly was instituted after other causes of hyperprolactinemia were ruled out. The dose was reduced after 3 months and her serum prolactin remained normal.
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)
