Imipramine use while Breastfeeding

Drugs containing Imipramine: Tofranil, Tofranil-PM

Imipramine Levels and Effects while Breastfeeding

Summary of Use during Lactation

Milk levels of imipramine and its metabolite are low and have not been detected in the serum of breastfed infants. Immediate side effects have not been reported and a limited amount of follow-up has found no adverse effects on infant growth and development. Imipramine use during breastfeeding would usually not be expected to cause any adverse effects in breastfed infants, especially if the infant is older than 2 months. Some experts consider imipramine one of the antidepressants of choice for nursing mothers.[1][2] Other agents with may be preferred when large doses are required or while nursing a newborn or preterm infant.

Drug Levels

Imipramine is metabolized to desipramine which has antidepressant activity equal to that of imipramine. Desipramine is metabolized to 2-hydroxydesipramine which has antidepressant activity equal to that of desipramine.[3]

Maternal Levels Two women who were taking imipramine 50 mg daily for panic disorder had imipramine and desipramine breastmilk levels measured 1 month postpartum (time after dose not stated). In one, levels of impiramine and desipramine were 91 and 185 mcg/L, respectively. In the other only trace quantities were detected.[4]

A mother who was 1 month postpartum began taking imipramine for depression. Sixteen days after initiation, milk imipramine plus desipramine levels ranged from 21 to 59 mcg/L at various times while taking a dose of 200 mg daily. There was no clear-cut relationship of milk levels to the time since the dose.[5]

Four mothers who were taking imipramine in doses of 75 to 150 mg daily had milk samples taken 12 to 15 hours after their daily dose. Milk imipramine plus desipramine levels ranged from 48 to 622 mcg/L, with little correlation to dosage. Foremilk levels were lower than hindmilk levels.[6] Using the hindmilk data from this study, an exclusively breastfed infant would receive an estimated maximum of 2.9% of the maternal weight-adjusted dosage.

Infant Levels Two infants had serum level measurements of imipramine plus desipramine while breastfeeding. One infant whose mother began imipramine 75 mg daily 2 weeks postpartum and was breastfed for 7 weeks had a serum level of 0.6 mcg/L. Another infant was breastfed for 17 weeks after his mother began imipramine 100 mg daily 8 weeks postpartum and later decreased to 75 mg daily. His average of 3 serum levels was 5.5 mcg/L (range 3.3 to 7.4 mcg/L). Time after the dose was not stated.[6]

One 5.9-week-old infant who was breastfed 10 to 12 times daily had no detectable serum imipramine or desipramine (both <25 mcg/L) during maternal use of imipramine 75 mg daily. Another 17-week-old infant who was breastfed 10 to 12 times daily had no detectable serum imipramine (<20 mcg/L) or desipramine (<35 mcg/L) during maternal use of imipramine 150 mg daily.[7]

Effects in Breastfed Infants

No behavioral or physical changes were noted in a 6-week-old breastfed infant whose mother had been taking imipramine 200 mg/day at bedtime for 15 days.[5]

Follow-up for 1 to 3 years in 14 breastfed infants whose mothers were taking imipramine in an average dosage of 161 mg daily (range 125 to 225 mg daily) found no adverse effects on growth and development.. [8]

Four infants were breastfed for 7 to 18 weeks during maternal use of imipramine 75 to 150 mg daily starting at 2 weeks (3 infants) and 8 weeks (1 infant) postpartum. Formal testing indicated no adverse effects on infant development up to 30 months of age. The mother of 1 infant was taking haloperidol along with imipramine 150 mg daily.[6]

In another study, 25 infants whose mothers took a tricyclic antidepressant during pregnancy and lactation were tested formally between 15 to 71 months and found to have normal growth and development. Some of the mothers were taking imipramine.[9]

Possible Effects on Lactation

Imipramine has caused increased prolactin levels and gynecomastia in nonpregnant, nonnursing patients.[10][11] Galactorrhea has been reported rarely.[12][13] The clinical relevance of these findings in nursing mothers is not known. The prolactin level in a mother with established lactation may not affect her ability to breastfeed.

Alternate Drugs to Consider

Nortriptyline, Paroxetine, Sertraline

References

1. di Scalea TL, Wisner KL. Pharmacotherapy of postpartum depression. Expert Opin Pharmacother. 2009;10:2593-607. PMID: 19874247

2. National Health Service (England). National Institute for Health and Clinical Excellence. Antenatal and postnatal mental health: clinical management and service guidance, clinical guideline no. 45. 2007. http://www.nice.org.uk/nicemedia/pdf/CG045NICEGuidelineCorrected.pdf

3. Weissman AM, Levy BT, Hartz AJ et al. Pooled analysis of antidepressant levels in lactating mothers, breast milk, and nursing infants. Am J Psychiatry. 2004;161:1066-78. PMID: 15169695

4. Ware MR, DeVane CL. Imipramine treatment of panic disorder during pregnancy. J Clin Psychiatry. 1990;51:482-4. PMID: 2228984

5. Sovner R, Orsulak PJ. Excretion of imipramine and desipramine in human breast milk. Am J Psychiatry. 1979;136:451-2. PMID: 426114

6. Yoshida K, Smith B, Craggs M et al. Investigation of pharmacokinetics and possible adverse effects in infants exposed to tricyclic antidepressants in breast-milk. J Affective Disord. 1997;43:225-37. PMID: 9186793

7. Birnbaum CS, Cohen LS, Bailey JW et al. Serum concentrations of antidepressants and benzodiazepines in nursing infants: a case series. Pediatrics. 1999;104:e11. PMID: 10390297

8. Misri S, Sivertz K. Tricyclic drugs in pregnancy and lactation: a preliminary report. Int J Psychiatry Med. 1991;21:157-71. PMID: 1894455

9. Nulman I, Rovet J, Stewart DE et al. Child development following exposure to tricyclic antidepressants or fluoxetine throughout fetal life: a prospective, controlled study. Am J Psychiatry. 2002;159:1889-95. PMID: 12411224

10. Turkington RW. Prolactin secretion in patients treated with various drugs: phenothiazines, tricyclic antidepressants, reserpine, and methyldopa. Arch Intern Med. 1972;130:349-54. PMID: 4560178

11. Turkington RW. Serum prolactin levels in patients with gynecomastia. J Clin Endocrinol Metab. 1972;34:62-6. PMID: 5061776

12. Klein JJ SRWR. Galactorrhea due to imipramine. Report of a case. N Engl J Med. 1964;271:510-2. PMID: 14172465

13. Mahasuar R, Majhi P, Ravan JR. Euprolactinemic galactorrhea associated with use of imipramine and escitalopram in a postmenopausal woman. Gen Hosp Psychiatry. 2010;32:341.e11-3. PMID: 20430243

Imipramine Identification

Substance Name

Imipramine

CAS Registry Number

50-49-7

Drug Class

  • Antidepressants
  • Antidepressive Agents, Tricyclic
  • Adrenergic Uptake Inhibitors

Administrative Information

LactMed Record Number

318

Information from the National Library of Medicine's LactMed Database.

Last Revision Date

2013-09-07

Disclaimer

Information presented in this database is not meant as a substitute for professional judgment. You should consult your healthcare provider for breastfeeding advice related to your particular situation. The U.S. government does not warrant or assume any liability or responsibility for the accuracy or completeness of the information on this Site.

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