Is Dothiepin safe while breastfeeding?

Effects on the breastfed infant

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.[ 3 ] 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.[ 6 ] 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.[ 5 ]

Effects on milk supply

Galactorrhea has been reported in one woman taking dothiepin.[ 7 ] 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.[ 8 ] 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.[ 9 ] 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 bre

Levels in milk

Dothiepin is metabolized to northiaden (nordothiepin), dothiepin-S-oxide and northiaden-S-oxide. The metabolites are estimated to have activity of about 50% of dothiepin's.[ 1 ] Maternal Levels. A woman was taking dothiepin 25 mg 3 times daily and clorazepate potassium 15 mg at bedtime. A breastmilk sample was obtained 3 hours after the second dose of the day. The dothiepin breastmilk concentration was 33 mcg/L. Another woman who had taken a total of 300 mg of dothiepin over 6 days had a breastmilk dothiepin concentration of 10 mcg/L, but sample collection time was not reported. Metabolites were not measured in either patient.[ 2 ] Eight women who were receiving dothiepin for depression provided breastmilk samples immediately before and after breastfeeding using a breast pump. Maternal dosages ranged from 25 to 225 mg daily (0.38 to 4.5 mg/kg daily) and the duration of therapy ranged from 2 days to more than 5 years. Dothiepin and its metabolites, northiaden, dothiepin-S-oxide and northiaden-S-oxide were measured in milk. The authors calculated weight-adjusted percentages of maternal dosages as follows: 0.58% for dothiepin, 0.23% for nordothiepin, 2.47% for dothiepin-S-oxide and 1.17% for nordothiepin-S-oxide.[ 3 ] Twenty lactating women were taking oral dothiepin once daily for depression in daily dosages of 75 mg to 225 mg. Milk samples were collected 10 to 14 hours after the previous dose of dothiepin which had been constant for at least 12 days. A total of 38 breastmilk samples were obtained because some women donated samples more than once. Dothiepin milk levels ranged from undetectable ( 10 mcg/L) to 95 mcg/L and northiaden milk levels ranged from undetectable ( 10 mcg/L) to 60 mcg/L with wide variability in both. No statistical difference was found between foremilk and hindmilk levels.[ 4 ] Two mothers with depression who were taking dothiepin had milk samples taken 12 to 15 hours after their daily dose. Milk dothiepin levels were measured by gas chromatograp

Alternatives LactMed lists

• Nortriptyline
• Paroxetine
• Sertraline