Summary of Use during Lactation

Limited information indicates that trazodone levels in milk are low and would not be expected to cause any adverse effects in breastfed infants, especially if the infant is older than 2 months or when doses of 100 mg or less are used at bedtime for sleep. A safety scoring system finds trazodone use to be possible to use cautiously during breastfeeding.[1]

Drug Levels

Maternal Levels. Six women who were 3 to 8 months postpartum were given 50 mg of trazodone orally and milk samples were taken for 30 hours after administration. Peak trazodone milk levels averaging about 110 mcg/L occurred 2 hours after the dose and milk levels declined with an average half-life of 7.5 hours (range 5.2 to 12.3 hours). The authors estimated that an exclusively breastfed infant would receive a dose of 0.005 mg/kg with this maternal dose or 0.65% of the maternal weight-adjusted dosage.[2] However, this study did not measure the active metabolite of trazodone in milk.

One woman who was 6.5 weeks postpartum and taking trazodone 75 mg daily had her milk measured at an unreported time after her dose. The trazodone concentration in her milk was 40 mcg/L.[3]

A woman took tradodone 50 mg daily at bedtime throughout pregnancy and lactation. She was also taking etizolam 0.5 to 1 mg daily. Breast milk samples were collected 4 times on days 5 and 6 postpartum. Trazodone and its metabolite 1-m-chlorophenylpiperazine (mCPP) milk concentrations measured at 7.2 hours after a dose were 50.2 and 3.2 mcg/L; concentrations at 18.9 hours after the dose were 21.2 and 1.3 mcg/L; concentrations at 20.4 hours after the dose were 18.2 and 0.9 mcg/L; concentrations on day 6 at 29 hours after the dose were 8 and <0.2 mcg/L.[4]

Infant Levels. Relevant published information was not found as of the revision date.

Effects in Breastfed Infants

One woman was 6.5 weeks postpartum and taking trazodone 75 mg, venlafaxine 75 mg and quetiapine 75 mg daily before conception, during pregnancy and during breastfeeding. Her breastfed infant's development was tested at 12 months of age with the Bayley Scales. Measurements were within normal limits on the mental, psychomotor and behavior scales.[3]

One infant whose mother took trazodone 200 mg daily for 12 weeks starting at 4 weeks postpartum was followed up at 12 months of age. No adverse effects on growth and development were found.[5]

One exclusively breastfed 15-week-old infant was breastfed during maternal therapy with trazodone 100 mg daily and venlafaxine 150 mg daily. No adverse reactions were reported by the mother or found in the medical records.[6]

A woman took etizolam 1 mg and trazodone 50 mg once daily for 3 months postpartum. Her infant was over 50% breastfed and demonstrated no adverse reactions at the 1- and 3-month checkups. The infant’s Denver Developmental Screening Test II was normal at 6 months of age.[4,7]

Effects on Lactation and Breastmilk

A nonpregnant woman with depression was treated with citalopram 20 mg daily, then 40 mg daily. Trazodone 50 mg at bedtime was added to treat insomnia and then increased to 100 mg at bedtime. One week later the patient noticed milk leakage from her breasts, which stained her clothing. Her serum prolactin was somewhat elevated, but no other abnormalities were noted. The trazodone dosage was tapered and then discontinued. One month later, the galactorrhea had resolved and her serum prolactin was in the normal range.[8]

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.[9] 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.[10] None of the mothers were taking trazodone.

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.[11]

Alternate Drugs to Consider

Nortriptyline, Paroxetine, Sertraline

References

1.

Uguz F. A new safety scoring system for the use of psychotropic drugs during lactation. Am J Ther. 2021;28:e118–e126. [PubMed: 30601177]

2.

Verbeeck RK, Ross SG, McKenna EA. Excretion of trazodone in breast milk. Br J Clin Pharmacol. 1986;22:367–70. [PMC free article: PMC1401139] [PubMed: 3768252]

3.

Misri S, Corral M, Wardrop AA, et al. Quetiapine augmentation in lactation: A series of case reports. J Clin Psychopharmacol. 2006;26:508–11. [PubMed: 16974194]

4.

Saito J, Ishii M, Mito A, et al. Trazodone levels in maternal serum, cord blood, breast milk, and neonatal serum. Breastfeed Med. 2021;16:922–5. [PMC free article: PMC8817729] [PubMed: 34348038]

5.

Misri S, Sivertz K. Tricyclic drugs in pregnancy and lactation: A preliminary report. Int J Psychiatry Med. 1991;21:157–71. [PubMed: 1894455]

6.

Newport DJ, Ritchie JC, Knight BT, et al. Venlafaxine in human breast milk and nursing infant plasma: Determination of exposure. J Clin Psychiatry. 2009;70:1304–10. [PubMed: 19607765]

7.

Saito J, Ishii M, Mito A, et al. Etizolam levels in maternal serum, cord blood, and breast milk during pregnancy and lactation: A case report. Psychiatry Clin Neurosci. 2021;75:211–2. [PubMed: 33733552]

8.

Arslan FC, Uysal EK, Ozkorumak E, et al. Trazodone induced galactorrhea: A case report. Gen Hosp Psychiatry. 2015;37:373.e1–2. [PubMed: 25920951]

9.

Venkatesh KK, Castro VM, Perlis RH, et al. Impact of antidepressant treatment during pregnancy on obstetric outcomes among women previously treated for depression: An observational cohort study. J Perinatol. 2017;37:1003–9. [PMC free article: PMC10034861] [PubMed: 28682318]

10.

Leggett C, Costi L, Morrison JL, et al. Antidepressant use in late gestation and breastfeeding rates at discharge from hospital. J Hum Lact. 2017;33:701–9. [PubMed: 28984528]

11.

Grzeskowiak LE, Saha MR, Nordeng H, et al. Perinatal antidepressant use and breastfeeding outcomes: Findings from the Norwegian Mother, Father and Child Cohort Study. Acta Obstet Gynecol Scand. 2022;101:344–54. [PMC free article: PMC9564556] [PubMed: 35170756]

Substance Name

Trazodone

CAS Registry Number

19794-93-5

Drug Class

Breast Feeding

Lactation

Milk, Human

Antidepressive Agents

Serotonin Uptake Inhibitors