Poor Feeding and Severe Sedation in a Newborn Nursed by a Mother on a Low Dose of Amitriptyline

Introduction

Depression, anxiety disorders, and sleep disturbances are frequently observed during the postpartum period. Very frequently, women with these clinical pictures need to use antidepressant medications. One of the most important questions about the use of medications during this period is the breastfeeding status. Similar to other psychotropics, antidepressants pass into breast milk. The concentration of antidepressants in the breast milk exhibits great variability between individual mothers and the type of drug used. ¹

Selective serotonin reuptake inhibitors (SSRIs) are the most commonly used antidepressants during the perinatal period. Therefore, there is extensive data published in the literature about the use of SSRIs during breastfeeding. Less data are available on the use of tricyclic antidepressants (TCAs) during the lactation period, although these antidepressants have been used much before SSRIs were used. Amitriptyline/nortriptyline is the TCA with the most extensive data on use during breastfeeding. In addition to no reported adverse events and no developmental delay in infants exposed to amitriptyline/nortriptyline at doses as high as 175 mg/day, infant plasma levels have been reported to be mostly below detection limits.^2,3 Contrary to these observations, this case report presents severe sedation and secondary poor feeding in an infant whose mother was treated with low-dose amitriptyline.

Case Report

A 27-year-old breastfeeding woman with a 15-day-old baby was admitted to the psychiatry outpatient clinic of a university hospital with complaints of severe insomnia along with secondary anxiety. She had no history of psychiatric disorder before or during pregnancy. The patient described that sleep disturbances occurred at the fifth day postpartum with a subsequent gradual increase. The patient reported that although the baby was healthy, the total duration of her sleep was only 2 hours in the past 3 days. Psychiatric interview conducted according to the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) (SCID-I), ⁴ indicated that the patient currently had only primary insomnia but no mood, anxiety, or psychotic disorders. Significant anxiety symptoms existed in the patient in the past 5 days.

Amitriptyline at 10 mg/day was administered to the patient. Three days later, the patient reported sleep duration of about 7 hours/day after the treatment. However, it was reported that the baby had severe sedation and poor feeding secondary to sedation for 2 days. According to the mother, the baby was almost continuously sleepy; the number of feeds per day and the breastfeeding duration decreased by about 80% compared with that before the treatment. The examination of the baby by a pediatrician and laboratory tests including hemogram parameters and biochemistry parameters suggested that the baby did not have any illness that could have resulted in these symptoms. Amitriptyline was discontinued in the mother, and the adverse events in the baby decreased without any specific treatment within 24 hours, and completely resolved within 48 hours. No complications such as dehydration and hypoglycemia were observed in the baby because of poor feeding. When the mother was started on amitriptyline at 10 mg/day again, the same adverse events recurred in the baby. The medication was discontinued at the request of the patient and her husband. Similar to the initial treatment, the adverse events in the infant were completely resolved at the end of 48 hours after discontinuation of the medication. During the initial challenge and rechallenge, the time course of initiation of adverse events to complete resolution in the infant was 4 days. A psychiatric interview carried out 1 week after the discontinuation of amitriptyline did not determine any psychiatric disorder in the mother. The mother reported a sleep duration of about 5 hours/day without any natural products and drugs.

Discussion

This appears to be the first report of significant side effects of maternal use of amitriptyline on a breastfed baby. The available reports suggest no detrimental events in breastfed infants exposed to maternal amitriptyline at doses of 75–175 mg/day. ² In contrast, it is well known that sedation is a frequently observed side effect of amtriptyline in adults. For this reason, amitriptyline at a lower dose of 10 mg/day was started.

The most widely reported side effects in babies exposed to antidepressants through breastfeeding are irritability, feeding and sleep disturbances, agitation, and sedation.^5–7 In the current case, a marked reduction in feeding of the infant secondary to severe sedation was observed. This was an unexpected event; because the maternal dose of amitriptyline was very low, no other medical reason for these symptoms in the baby could be established. Moreover, there was a temporal connection between the adverse events and initiation of the medication. Therefore, it was hypothesized that the sedation and poor feeding in the infant were associated with the maternal use of amitriptyline. It was confirmed by recurrence of the symptoms after the second administration of amitriptyline. The adverse events could be incidental and may have resulted from a high variability in the milk to plasma (M/P) ratio of antidepressants between users during lactation, although studies suggest that levels of amitriptyline and its metabolites in milk are low.^1,8,9 Drugs and lactation database (LactMed) ⁹ suggest that use of amitriptyline during breastfeeding appears not to be associated with any adverse effects in breastfed infants, especially if the infant is older than 2 months. In the current case, the infant was only 15 days old. This could be another reason for the adverse events reported in this case.

In conclusion, this case report suggests that even at low dose, amitriptyline may adversely affect some infants exposed to the drug during the lactation period. Further studies and case reports on the safety of amitriptyline in breastfed infants are needed.