Liver test abnormalities have been reported to occur in up to 16% of patients being treated with tricyclic antidepressants, but elevations are uncommonly above 3 times the upper limit of normal. The aminotransferase abnormalities are usually mild, asymptomatic and transient, reversing even with continuation of medication. Rare instances of clinically apparent acute liver injury have been reported due to doxepin, but the number of cases have been too few to characterize the clinical features. Recurrent jaundice and marked aminotransferase elevations with repeated exposures to doxepin has been reported. Most cases have been mild and deaths from acute liver failure or chronic injury have not been reported.
◉ Summary of Use during Lactation:Because of its sedating potential, active metabolite, presence in infant serum, two reports of adverse effects in breastfed infants, and only one report of use without apparent adverse reactions, doxepin is a poor choice and other agents are preferred, especially while nursing a newborn or preterm infant. A safety scoring system finds doxepin to be not recommended during breastfeeding.
Maternal use of topical doxepin cream is unlikely to pose a problem for a breastfed infant as long as it is applied away from the breasts so that the infant cannot ingest the drug directly.
◉ Effects in Breastfed Infants:One infant was breastfed (extent not stated) over a 2-month period during maternal use of doxepin 150 mg at bedtime, beginning at 30 days postpartum. The infant experienced no apparent adverse reactions.
One infant had an adverse reaction that was probably caused by doxepin in breastmilk. An 8-week old breastfed infant was found pale, limp, somnolent and almost not breathing 4 days after the maternal dosage had been increased from 10 mg daily to 25 mg three times daily. The infant returned to normal 24 hours after discontinuing breastfeeding.
A 9-day-old breastfed infant had poor sucking and swallowing, hypotonia, vomiting, and weight loss. The reaction was probably caused by doxepin in breastmilk. The infant's mother was taking 35 mg of doxepin at bedtime daily.
◉ Effects on Lactation and Breastmilk: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 doxepin.
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.
◈ What is doxepin?
Doxepin is a tricyclic antidepressant that has been used to treat alcoholism, anxiety, depression, and insomnia (trouble sleeping). As a cream, it has been used for short-term treatment of itchiness. Some brand names include Quitaxon®, Prudoxin®, Silenor®, Sinequan®, and Zonalon®. It is also sold as a combination drug with another medication called levomenthol under the brand name Doxure®.Sometimes when people find out they are pregnant, they think about changing how they take their medication, or stopping their medication altogether. However, it is important to talk with your healthcare providers before making any changes to how you take this medication. Your healthcare providers can talk with you about the benefits of treating your condition and the risks of untreated illness during pregnancy.
◈ I take doxepin. Can it make it harder for me to get pregnant?
It is not known if doxepin can make it harder to get pregnant.
◈ Does taking doxepin increase the chance for miscarriage?
Miscarriage is common and can occur in any pregnancy for many different reasons. Based on the studies reviewed, it is not known if doxepin increases the chance for miscarriage.
◈ Does taking doxepin increase the chance of birth defects?
Every pregnancy starts out with a 3-5% chance of having a birth defect. This is called the background risk. Based on the studies reviewed, it is not known if doxepin increases the chance of birth defects. Data from animal studies does not suggest an increased chance for birth defects. In a case series looking at 8 human pregnancies, there were no birth defects reported.
◈ Does taking doxepin in pregnancy increase the chance of other pregnancy-related problems?
Based on the studies reviewed, it is not known if doxepin can cause other pregnancy-related problems, such as preterm delivery (birth before week 37) or low birth weight (weighing less than 5 pounds, 8 ounces [2500 grams] at birth).
◈ I need to take doxepin throughout my entire pregnancy. Will it cause withdrawal symptoms in my baby after birth?
The use of tricyclic antidepressants during pregnancy can cause temporary symptoms in newborns soon after birth. These symptoms are sometimes referred to as withdrawal. Symptoms reported with other tricyclic antidepressants include jitteriness, vomiting, crying, fussiness, changes in sleep patterns, tremors, trouble with eating and/or regulating body temperature. In most cases these symptoms were mild and went away on their own within a week or two after birth. Not all babies exposed to tricyclic antidepressants will have these symptoms. It is not known if taking doxepin during pregnancy can cause symptoms in newborns. However, it is important that your healthcare providers know you are taking doxepin so that if symptoms occur your baby can get the care that is best for them.
◈ Does taking doxepin in pregnancy affect future behavior or learning for the child?
Based on the studies reviewed, it is not known if doxepin increases the chance for behavior or learning issues.
◈ Breastfeeding while taking doxepin:
Doxepin gets into breastmilk in small amounts. Information about the use of doxepin while breastfeeding is limited. There are two case reports of respiratory depression (trouble breathing) in babies who were exposed to doxepin through breastmilk. If you suspect the baby has any symptoms (trouble breathing, is not gaining weight, has constipation, or is very sleepy), contact the child’s healthcare provider. Be sure to talk to your healthcare provider about all of your breastfeeding questions.
◈ If a male takes doxepin, could it affect fertility (ability to get partner pregnant) or increase the chance of birth defects?
Based on the studies reviewed, it is not known if doxepin could affect fertility or increase the chance of birth defects above the background risk. In general, exposures that fathers or sperm donors have are unlikely to increase the risks to a pregnancy. For more information, please see the MotherToBaby fact sheet Paternal Exposures at https://mothertobaby.org/fact-sheets/paternal-exposures-pregnancy/.A pregnancy registry for psychiatric medications, including this one, has been organized at the Massachusetts General Hospital. Contact the registry at https://womensmentalhealth.org/clinical-and-research-programs/pregnancyregistry/.
The pharmacokinetics of doxepin have not been extensively studied, but the drug is well absorbed from the GI tract in animals. Peak plasma concentrations occur within 2 hours after oral administration of the drug.
Limited data indicate that doxepin and its active N-demethylated metabolite are distributed into milk in concentrations reportedly ranging from about 30-140% and 10-115%, respectively, of those in maternal serum and that substantial concentrations of the active metabolite have been detected in the serum and urine of nursing infants whose mothers were receiving 75-150 mg daily.
