Abstract
Sleep disorders are not uncommon during breastfeeding. Several nonpharmacologic strategies that can be helpful include good sleep hygiene, such as establishing regular sleep–wake cycles, stimulus control, minimizing fluid intake before bed to decrease nocturia, avoiding caffeine intake close to bedtime, addressing physical discomfort, cognitive behavioral therapy, exercise, meditation, and acupuncture. 1
If these methods are unsatisfactory, a medication may be used. An important caveat is that taking a medication that reduces alertness by a mother who is sharing a bed with an infant is at risk for sudden infant death syndrome.2,3 Although most guidelines mention only alcohol, smoking and illicit drugs as risk factors, at least one infant death from overlying and infant sedation was reported in a nursing mother who was taking phenytoin and the sedating drug primidone for epilepsy and sharing her bed with her 13-day-old infant. 4 Bed sharing while using a sleep medication should be avoided, especially with infants under 4 months of age. 3
When a medication is used, taking the bedtime dose after the infant's last feeding of the day may minimize the dose received by an older infant who is sleeping through the night. It is good practice to monitor exposed infants for excess sedation, hypotonia, and respiratory depression. More detailed information and references on specific medications can be found in the corresponding LactMed records.
Benzodiazepines
Lorazepam
Lorazepam has the most information on use during breastfeeding among benzodiazepines. It has low levels in breast milk, a shorter half-life than many other benzodiazepines, and it is safely administered directly to infants. Evidence from about 70 nursing mothers indicates that lorazepam does not cause any adverse effects in breastfed infants with usual maternal dosages. However, one case report indicated that lorazepam contributed to sedation in a breastfed infant whose mother was also taking risperidone.
Temazepam
Temazepam has low to undetectable levels in breast milk with usual maternal doses. In two breastfed infants whose mothers were taking temazepam, the drug and its metabolite oxazepam were undetectable in infant plasma. Temazepam also has a relatively short half-life, so it would not be expected to cause any adverse effects in breastfed infants.
Triazolam
Triazolam has a short half-life, so occasional use while breastfeeding an older infant should pose little risk to the infant. However, little information is available on the use of triazolam during breastfeeding, so an alternate hypnotic may be preferred, especially while nursing a newborn or preterm infant.
Long-acting benzodiazepines
Long-acting drugs, such as diazepam and chlordiazepoxide, are unsuitable for use as hypnotics in nursing mothers. Diazepam and its active metabolite nordazepam are both measurable in milk and in the serum of breastfed infants and sedation has been reported in several infants during maternal diazepam use. Because the half-lives of diazepam and nordiazepam are long, timing breastfeeding with respect to the dose is of little benefit in reducing infant exposure.
Little to no information is available on the use of several other long-acting benzodiazepine hypnotics during breastfeeding, including clonazepam, estazolam, flurazepam, and quazepam. Alternate hypnotics are preferred, especially while nursing a newborn or preterm infant.
The “Z Drugs”
This nonpharmacologic category refers to three nonbenzodiazepine hypnotics whose names start with the letter z. Although not chemically benzodiazepines, these drugs do act at some of the same receptors as benzodiazepines, with varying degrees of selectivity. Eszopiclone (S-zopiclone) binds nonselectively to benzodiazepine or gamma-aminobutyric acid (GABA)-A receptors, whereas zaleplon and zolpidem selectively bind to the omega-1 subunit of the GABA-A receptor.
Zolpidem
The manufacturer of zolpidem reports cases of sedation in breastfed infants whose mothers were taking zolpidem and some expert opinion considers zolpidem not to be recommended during breastfeeding. The manufacturer gives the nonbreastfeeding-friendly advice of, “A lactating woman may consider interrupting breastfeeding and pumping and discarding breast milk during treatment and for 23 hours after zolpidem administration in order to minimize drug exposure to a breast fed infant.”
Published information does not support these concerns. Five nursing mothers who were 3–4 days postpartum were given a single oral dose of zolpidem 20 mg. Milk collected 3 hours after the dose contained between 0.76 and 3.88 mcg of zolpidem, which corresponds to 0.004% to 0.019% of the maternal dosage. The drug was undetectable in milk 13 and 16 hours after the dose. Because of the low levels of zolpidem in breast milk and its short half-life, it would not be expected to cause any adverse effects in older breastfed infants, but should probably be avoided while breastfeeding neonates.
Zaleplon
Little information is available on the use of zaleplon during breastfeeding. Five nursing mothers who were at least 14 days postpartum were given a single oral dose of zaleplon 10 mg. Using the peak milk level data from this study, an exclusively breastfed infant would receive an estimated maximum of 2.1 mcg/kg daily with this maternal dosage regimen or a relative infant dose of 1.4%. The mean half-life in milk was 1.1 hours. The low levels of zaleplon in breast milk and its short half-life indicate that amounts ingested by the infant are small and would not be expected to cause any adverse effects in older breastfed infants.
Eszopiclone
No data are available on the use of eszopiclone during breastfeeding. Data from the racemate, zopiclone, indicate that occasional use while breastfeeding an older infant should pose little risk to the infant. Because of its relatively long half-life of 5 hours, an alternate hypnotic may be preferred, especially while nursing a newborn or preterm infant.
Melatonin Receptor Agonists
Melatonin
Melatonin is a normal component of human milk. Concentrations in milk are higher during nighttime than during the daytime with a peak around 3 am. It plays a role in regulating sleep and circadian rhythm in infants as well as a possible role in gut–brain signaling. Some authors suggest that mothers should nurse in the dark at night to avoid reductions in the melatonin content of breast milk, which could disturb infant sleep patterns. Differentiating milk pumped during the day from milk pumped during darkness has also been suggested for women pumping milk for their infants. Some studies have attributed longer sleep time in breastfed infants than in formula-fed infants to melatonin in breast milk.
Few data exist on the safety of maternal use of exogenous melatonin during breastfeeding. Some authors recommend against the use of melatonin in breastfeeding because of the lack of data and a relatively long half-life in preterm neonates. Nevertheless, doses higher than those expected in breast milk after maternal intake have been used safely in infants. It is unlikely that short-term use of usual doses of melatonin in the evening by a nursing mother would adversely affect her breastfed infant.
There is a report of an 18-month-old breastfed infant who had been having bleeding episodes since birth. A platelet aggregation test showed that the infant had reduced platelet aggregation after breastfeeding. When the infant was fasting, platelet aggregation was normal. The infant's mother was occasionally taking melatonin for sleep. After she stopped melatonin intake for 3 months, the infant's platelet aggregation became normal and the infant had no further bleeding episodes.
Ramelteon
Ramelteon is a synthetic melatonin receptor agonist. It undergoes rapid and almost complete first-pass metabolism to several metabolites. The principle active metabolite has an elimination half-life of 2–5 hours in adults. A nursing mother was taking oral ramelteon 8 mg nightly for sleep postpartum. Breast milk concentrations of ramelteon and its active metabolite were measured daily during the first 3 days postpartum at various times after a dose. The authors extrapolated their results to older infants, indicating that a fully breastfed infant would receive only 0.24% of the mother's weight-adjusted dosage.
Ramelteon may have an effect on serum prolactin levels. Prolactin levels increased by 4.9 mcg/L (34%) in nonbreastfeeding women with chronic insomnia who were taking ramelteon 16 mg nightly for 6 months, although no clinical symptoms of hyperprolactinemia were reported. Because of the minimal amount of information available, another drug may be preferred.
Tasimelteon
Tasimelteon is a newer synthetic melatonin-receptor agonist. No information is available on the use of tasimelteon during breastfeeding, so other drugs are preferred.
Antidepressants
Some antidepressants are used at nighttime for sleep because of their sedating properties. Although they are not first-line agents, they may be useful in some patients.
Amitriptyline
Milk levels of amitriptyline and its metabolites are low and infant serum levels are low to nondetectable with antidepressant dosages. Infant sedation has been reported occasionally with maternal antidepressant dosages, but a limited amount of follow-up has found no adverse effects on infant growth and development. The lower doses used for insomnia should pose minimal risk to nursing infants.
Doxepin
A 9-day-old breastfed infant had poor sucking and swallowing, hypotonia, vomiting, and weight loss that was probably caused by doxepin in breast milk. The infant's mother was taking 35 mg of doxepin at bedtime daily. Another 8-week-old breastfed infant was found pale, limp, somnolent, and almost not breathing 4 days after the maternal doxepin dosage had been increased from 10 mg daily to 25 mg three times daily. The infant returned to normal 24 hours after discontinuing breastfeeding. Because of its sedating potential, active metabolite, presence in infant serum, and documented adverse effects, doxepin should be avoided during breastfeeding.
Trazodone
Trazodone levels in milk appear to be low and no adverse reactions occurred in a few case reports. Trazodone is not expected to cause adverse effects in breastfed infants, especially in infants older than 2 months or when doses of 100 mg or less are used at bedtime for sleep.
Antihistamines
Antihistamines that cause a high degree of sedation are used as hypnotics, but they are not drugs of choice for treating insomnia for several reasons. Tachyphylaxis to sedation can occur with repeated daily use. Also, antihistamines in relatively high doses given by injection can decrease basal serum prolactin, although suckling-induced prolactin secretion is not affected by antihistamine pretreatment of postpartum mothers. Whether lower oral doses of antihistamines have the same effect on serum prolactin or whether the effects on prolactin have any consequences on breastfeeding success have not been studied.
Diphenhydramine
Diphenhydramine is found in many over-the-counter sleep preparations. Occasional doses of 25 mg of diphenhydramine would not be expected to cause any adverse effects in breastfed infants, although mild drowsiness was reported in 1 infant of 12 exposed to diphenhydramine in breast milk in a telephone survey of nursing mothers.
Hydroxyzine
Hydroxyzine is sometimes used off-label as a sedative. A French pharmacovigilance center found adverse reactions to it in 8 infants over a 26-year period. It was one of the drugs most often suspected in serious adverse reactions in breastfed infants, primarily sedation. It is not a good choice in nursing mothers.
Orexin Receptor Antagonists
This relatively new class of drugs works by the unique mechanism of blocking orexin neuropeptides from binding to their receptors. No information is available on the use of daridorexant, lemborexant, or suvorexant during breastfeeding. Because of their extensive plasma protein binding (daridorexant 99.7%, lemborexant 94%, suvorexant >99%), the amounts of these drugs in milk are likely to be small. They are not contraindicated in breastfeeding, but until more data become available, drugs from another class may be preferred.
Summary
Nonpharmacologic methods to improve sleep are preferred during breastfeeding, but medications can sometimes be useful. Although little lactation information is available on most sleep medications, short-acting benzodiazepines, such as lorazepam, as well as zaleplon and zolpidem appear to be acceptable. Melatonin and possibly ramelteon might be acceptable choices. The antidepressants, amitriptyline and trazodone, have a reasonable amount of safety data and can be used in low doses. Diphenhydramine can be used occasionally, but continuous daily use may not be advisable. It is best to avoid cosleeping with infants when sleep medications are being taken.
Footnotes
Disclosure Statement
No competing financial interests exist.
Funding Information
No funding was received for this article.