Transcript of BREASTFEEDING AND WOMEN’S MENTAL HEALTH
PowerPoint PresentationDepartment of Psychiatry
Disclosures Nothing to disclose, currently paid by Banner
University Medical Center, and on faculty
at University of Arizona.
breastfeeding Learn about literature available regarding
mood,
sleep and breastfeeding Know the resources available to refer to
regarding
pharmacology and breast feeding Understand principles of
psychopharmacology
involved in breastfeeding, including learning about some specific
medications, to be able to counsel a woman and obtain informed
consent
Be aware of syndrome described as Dysphoric Milk Ejection
Reflex
Lactation Physiology
AAP Material on Breastfeeding
Depression and Infant Care
Depressed mothers are: More likely to misread infant cues 64
Less likely to read to infant Less likely to follow proper safety
measures Less likely to follow preventative care advice 65
Depression is Associated with Decreased Chance of Breastfeeding A
review of 75 articles found “women with depressive symptomatology
in the early
postpartum period may be at increased risk for negative
infant-feeding outcomes including decreased breastfeeding duration,
increased breastfeeding difficulties, and decreased levels of
breastfeeding self-efficacy.” 1
Depressive Symptoms and Risk of Formula Feeding An Italian study
with 592 mothers participating by completing the Edinburgh
Postnatal
Depression Scale immediately after delivery and then feeding was
assessed at 12-14 weeks where asked if breast, formula or combo
feeding. Scores were significantly higher in the full bottle fed
group than the fully breastfed group (but average of both groups
was not in the depressive range). An increase of 1 point on the
EPDS correlated to a 6% chance of bottle feeding. 2
Excluded mothers taking antidepressants,
Depression and Post Partum Sleep A Norwegian study aimed to
estimate the prevalence of and risk factors for poor
maternal sleep and depression among 2830 post-partum women 3
Pittsburgh Quality Sleep Index (PSQI) was used to self rate sleep
complaints and the Edinburgh Postnatal Depression Scale (EPDS) was
used to measure depressive symptoms. Demographic info was obtained
from records. Moms would have been on maternity leave (44 weeks
paid in Norway) and info about breastfeeding and sleeping
arrangements were added.
57% above cut off for PQSI, and 16.5% for EPDS Multiple logistic
regression showed depression was the variable most strongly
associated with sleep problems. Went on to measure sleep using
actigraphy in a subset of mothers and there was no
difference in sleep between depressed and non depressed women
despite differences in the PSQI
How Do Babies Sleep? Henderson et al studied natural pattern of
infant sleep and found that by 3 months of
age 50 % of infants are sleeping from 24:00 until 05:00 AND
sleeping for 8 hours straight 5
Breastfeeding and Sleep Survey of sleep and fatigue administered to
6410 mothers in 59 countries. 4
Breastfeeding mothers reported significantly more sleep than mixed
or formula only fed (6.6, 6.4, and 6.3 hours).
Breast feeding mothers reported more energy than mixed or formula
feeding
Breastfeeding and Sleep Disturbances Doan et al studied parents of
infants and found that parents who breastfed (vs
formula) actually got 40-45 min more sleep per night as measured by
actigraphy and also self reported less sleep disturbances 6
Contraindications to Breastfeeding Maternal Abuse of street drugs
HIV T-Cell lymphotropic virus infection or Brucellosis Untreated
miliary TB Antimetabolite chemotherapy and ongoing radiation
therapy Active herpetic breast lesions
Infant Galactosemia
2012 revision of the American Academy of Pediatrics policy
statement on breastfeeding and the use of human milk
Considerations When Prescribing Medications in Pregnancy The need
for the drug by the mother The potential effects of the drug on
milk production The amount of the drug excreted into breast milk
The extent of absorption by the breast feeding infant The potential
adverse effects on the breast feeding infant
AAP publication: The Transfer of Drugs and Therapeutics into Human
Breast Milk: An Update on selected topics. Hari Cheryl Sachs and
Committee on Drugs. Pediatrics 2013; 132; e796.
Psychopharmacology and BF Safety The amount of medication to which
an infant is exposed depends on several factors: factors
pertaining to the specific medication, the maternal dosage of
medication, the frequency of maternal dosing as well as chronicity,
frequency of infant feedings, and the rate of maternal drug
metabolism
Age of the infant, and health status of the infant: During the
first few weeks of a full-term infant’s life, there is a lower
capacity for hepatic drug metabolism, which is about one-third to
one-fifth of the adult capacity. Over the next few months, the
capacity for hepatic metabolism increases significantly and, by
about 2 to 3 months of age, it surpasses that of adults.
Involve the pediatrician
Pump and Dump?
Lactation Risk Categories L1 Compatible: drug has been taken by a
large number of breastfeeding women without any observed
increase in adverse effects in the infant; controlled studies fail
to demonstrate a risk to the infant, or the product is not orally
bioavailable in an infant
L2 Probably compatible: drug has been studied in a limited number
of breastfeeding women without an increase in adverse effects in
the infant, and/or the evidence of a demonstrated risk is
remote
L3 Probably compatible: there are no controlled studies in
breastfeeding women; however, the risk of untoward effects to
breastfed infant is possible, or controlled studies show only
minimal non-threatening adverse effects; drugs should be given only
if potential benefit justifies potential risk to infant; new
medications that have no published data are automatically
categorized in this category, regardless of how safe they may
be
L4 Possibly hazardous: positive evidence of risk to breastfed
infant or to breast milk production; benefits of use may be
acceptable despite the risk to infant; e.g. if the drug is needed
in a life-threatening situation or a serious disease for which
safer drugs cannot be used or are ineffective
L5 Hazardous: studies in breastfeeding mothers have demonstrated
significant and documented risk to the infant based on human
experience, or is a medication that has a high risk of causing
significant damage to infant; drug is contraindicated in women
breastfeeding an infant
Resourses LactMed: toxnet.nlm.nih.gov/newtoxnet/lactmed.htm Infant
Risk Center: infantrisk.com MGH: Womensmentalhealth.org
Mothertobaby.org has fact sheets you can give to patient
Antidepressants and Lactation A small study compared milk secretory
activation between mothers taking
antidepressants and mothers who were not. Mothers taking
antidepressants had a delay of 16 hours, but no difference in
success of breastfeeding at 4 days 7
Online survey of 930 mothers who took an antidepressant during
pregnancy compared those who nursed while taking an antidepressant
to those who did not. Drug discontinuation was noted in 10% of
infants, and it was much less likely if mother continued
antidepressant while breastfeeding 14
Antidepressants MAOIs: Insufficient evidence, and as such not
recommended during nursing TCAs:
Amitriptyline and nortriptyline found in variable concentrations.
But no adverse effects reported. Also no adverse effects for the
small number of infants exposed to imipramine, desipramine,
clomipramine.
Doxepin:
In a case report of 2 infants exposed to doxepin both had high
levels in the milk, and one of those infants had respiratory
depression that resolved within 24 hours of cessation of
breastfeeding. 9 In other cases doxepin has been linked to infant
death.
Do not use DOXEPIN, linked with infant death in one case.
Antidepressants Sertraline:
Considered preferred. Concentrations of 0.5% down to 0.04% of
maternal dose in milk. Milk concentration did not correlate with
maternal dose. Drug concentrations are higher in hind milk. Peak
concentrations at 8-9 hours (pump and dump would reduce infant
expose by 17%). 10,11
Infant serum levels only detectable in 24% of infants, and
correlated with mother’s dose and inversely with infant age.
12
Meta-analysis found serum levels were nondetectable or negligible
and no adverse events reported 9
Once case of sleep myoclonus in a 4 month old, and one case of
agitation that spontaneously resolved 13,
Antidepressants Paroxetine:
Preferred medication. Undetectable or minimal concentration in
breastmilk 12
Meta-analysis of 37 infants exposed. Infant serum levels were
nondetectable in all but 3 cases which had low levels. No adverse
effects were reported 9
Multiple cases with no ill effect to infant In a study of mothers
who took paroxetine in the 3rd trimester and breastfed, about a
quarter reported
side effects such as decreased alertness, constipation, sleepiness,
and irritability 12
One study found 12% of infants of mothers taking paroxetine had
adverse events including insomnia, restlessness, crying and poor
feeding, all of which resolved within 3 days of discontinuing
paroxetine (or in one case decreasing the dose). 17
36 mothers on an avg dose of 20.4mg daily of paroxetine had infants
with normal 6 month weights and no abnormal effects 15
One case report of an infant with detectable serum paroxetine
levels who had 3 episodes of vomiting and dehydration. The infant
was thriving 6 weeks after breastfeeding was discontinued. 16
Antidepressants Fluoxetine: Meta-analysis compiled data from 238
infants on 15 antidepressants and found
fluoxetine had a relatively high infant serum levels (18% had
levels over 10% of maternal levels) 11
In a meta-analysis of 190 infants, serum levels varied from
undetectable to very high. The infant with the “very high” level
had excessive fussiness, decreased sleep, vomiting and diarrhea
that stopped when breastfeeding stopped. Infant serum levels did
not seem to correlate with maternal dose. 10 cases of adverse
events which were transient or confounded by multiple
medications.
One study looked at infants neurobehavioral development at 1 year
of age and found it to be normal. 9
Despite higher levels in breast milk most experts do not recommend
changing to breastfeed if on fluoxetine prenatally.
Antidepressants Citalopram and escitalopram:
Citalopram has relatively high infant serum levels 11
Several small reports of mothers taking citalopram show generally
low levels in infant serum, but with occasional higher levels which
may relate to mother being a poor metabolizer of CYP2C19. 17
One study looked at infants breastfed by mothers taking citalopram
and found normal weight and development at 1 year compared to
controls 11
Infant serum levels in infants whose mothers were taking
escitalopram where undetectable or very low 11
Several case reports of infants without adverse effects on
escitalopram, but also one report of an infant with irritability,
vomiting and fever with moderately elevated LFTs that improved 2
weeks after breastfeeding was discontinued and resolved 1 month
later. 20 Another report of a 5 day old exposed to escitalopram
both pre and postnatally admitted for necrotizing enterocolitis.
21
Antidepressants Venlafaxine, Desvenlafaxine, Duloxetine:
Venlafaxine: Infants had elevated rate of metabolites in all
infants studied of up to 37% 11
In 10 cases, 2 infants had decreased weight gain and the others had
no adverse effects. 9, 23
Desvenlafaxine: Levels of desvenlafaxine are about half that of
mothers who took venlafaxine. Babies exposed to desvenlafaxine (and
polypharmacy)were found to have lower growth rate 22
Duloxetine: has limited data looking at 2 infants. Thus far low
levels in milk and infant serum. Monitor infant growth rate
Antidepressants Mirtazapine:
Several case reports of infant serum levels that were either
undetectable or low. Case study of 8 infants found normal
development at around 6 months of age. 27
Antidepressants Bupropion:
8 case reports of which 7 found non detectable levels with both IR
and SR dosage. 1 case report where the mother of a 6 month old was
taking the XL formulation (along with escitalopram) and the infant
had a seizure. The infant had detectable but low levels of
bupropion and its metabolite hydroxybupropion 25,26,27,28
Antidepressants No data with vortioxetine, vilazodone,
brexpiprazole and levomilnacipran
Neurostimulation for Depression ECT: Acceptable option as
anesthetics and neuromuscular blockers such as propofol
and succinylcholine are acceptable with breastfeeding as soon as
the effects wear off TMS: No data
Mood Stabilizers Lithium:
No difference between fore and hind milk 31
Levels reported in 13 infants were all high (10-50% of maternal
levels), but no adverse effects reported except for one infant
exposed in utero with heart murmur, T wave inversion, cyanosis and
hypotonia whose mother was also on a diuretic
TSH elevated in 2 infants (one normalized despite continued
breastfeeding) who were exposed during pregnancy 32, 33
Need to monitor infant lithium concentration, TSH, renal function
and CBC AAP recommends using caution
Mood Stabilizers Valproate:
If not exposed during pregnancy infant serum levels were less than
6% of maternal levels (studies complicated by polypharmacy)
34
19 infants with no adverse effects, one infant with
thrombocytopenia and anemia which resolved when nursing stopped
(however could be explained by viral infection.) 35
One study compared IQ of children breastfed with valproic acid vs
formula fed by mother on valproic acid and found a statistically
different ihigher IQ in breastfed infants at age 6. 36
Monitor for bruising and jaundice, VPA level, platelets and liver
enzymes
Mood Stabilizers
Carbamazepine: Levels are detectable but low in breastmilk, limited
data on levels in infants not exposed during
pregnancy. One study looked at 54 breastfed infants and infant
serum levels ranged from undetectable to 70% of maternal levels of
carbamazepine, no correlation was found with maternal and infant
serum level . 37
Of 25 infants exposed through nursing 2 had transient hepatic
dysfunction (resolved when nursing was stopped) and both
demonstrated normal development at 6 months.
Monitor for jaundice, drowsiness, weight gain, and developmental
milestones. Check liver, bilirubin, CBC, and Carbamazepine
levels
Mood Stabilizers
Lamotrigine: Milk/Plasma ratio of 0.61 with infant serum
concentration of 30% of maternal concentrations38
No reports of infant SJS Multiple case reports without adverse
events Of 8 infants who had platelets monitored 7 were elevated
with no adverse event 40
A mother on 850mg daily had an infant have a severe apneic spell
requiring chest compressions. 41
Monitor for rash, respiratory depression, CBC, consider lamotrigine
levels
Antipsychotics Clozapine: Concentrated in breast milk 9
Infant serum levels 279% that of mother’s serum levels. Case
reports of infant with sedations, agranulocytosis, and
cardiovascular instability. Monitor for somnolence, CBC with diff
(weekly), NMS. Infant would go on clozapine
registry Probably best to avoid
Antipsychotics Olanzapine: Several reports of infant’s levels being
undetectable for mothers with doses up to 20 mg
daily, 1 case report with infant with detectable level. The
manufacture compiled 102 breastfed infants whose mother was taking
olanzapine
and 15% reported adverse events (somnolence, irritability, tremor
and insomnia) though many exposed prenatally also. 46-47
A case control study compared mothers who took olanzapine and
breastfed vs those who took the drug and did not breastfeed, vs
those taking Tylenol. Mothers completed a survey 1-2 years later
showing no statistical difference in the groups with regards to
development. 66
Probably preferred antipsychotic in breastfeeding
Antipsychotics Aripiprazole: Very limited data, Can lower prolactin
levels and several case reports of difficulty with establishing
supply. Only a handful of cases with doses around 15mg daily. One
case where serum levels
were detected the infant was exposed in utero. One case of a 3
month old infant who was growing normally, and one case a baby was
partially breastfed and at 4 months was reaching normal
developmental milestones. 42-44
One case of a 12 day old on lamotrigine, aripiprazole, sertraline
and synthroid presented with severe weight loss and dehydration who
developed DIC and required 5 toe amputation. 45
Probably pick another agent
Antipsychotics Risperidone: 4 case reports of infants breastfed
(mother’s dose up to 4mg daily) and infant levels
where undetectable. 48
No reports of adverse events (except sedation in a infant with
mother and significant polypharmacy). Several reports of normal
development. 49-52
Can cause galactorrhea
Antipsychotics Quetiapine: Probably a good choice during
breastfeeding, at least at low doses. Max milk levels 1 hour after
dose and correlated with maternal dose. 62 No difference in
fore vs hind milk. 63
A lot of the cases were moms on very low doses The few cases of
infant levels were below 10% All case reports did not note adverse
events, and development was within normal limits
for the cases in which it was reported.
Antipsychotics Haloperidol: Levels in infants of mothers on 5-20mg
collected. They had low levels present, not
related to dose. Several cases showed normal development and no
adverse effects, but one study with
haloperidol plus chlorpromazine showed 2 infants (out of 4) had a
decline in developmental scores at 12-18 months 53
Antipsychotics Ziprasidone has 1 case report of no adverse events
54
Asenapine, paliperidone, Iloperidone, and lurasidone have no
data
Lactation on an Inpatient Psychiatric Unit Is it safe? Is it wise?
Who gets to decide?
Insomnia Sleep hygiene Risk of mother falling asleep
Diphenhydramine: has surprisingly little data, but occasional use
is acceptable Trazadone: 0.6% maternal dose, and no reported
adverse events Zolpidem: variable levels in milk, one case of
infant sedation Eszopiclone: no data Melatonin: Limited data on
safety and infant plasma levels, but short term course is
unlikely to have negative effect.
Anxiolytics Buspirone: has insufficient data. One case report with
undetectable milk and infant serum levels.55
Hydroxyzine: Chronic use may effect milk supply, but occasional use
probably will not. No data on milk or serum concentrations. Of 174
mothers taking hydroxyzine there were 8 adverse events noted,
primarily sedation. 68
Motherisk Study included 124 infants exposed to benzodiazepines via
breastmilk, only 1.6% experienced sedation
Clonazepam: Not a preferred choice, associated with multiple
adverse events including serious adverse events.
Diazepam: Infant serum levels are unpredictable and can range from
unpredictable to very high. Associated with sedation and weight
loss making diazepam a poor choice. 56
Lorazepam: Low breast milk levels, safe to administer to infants,
no adverse effects noted in breastfed infants
(toxnet.nlm.nih.gov)
Oxazepam: has a short half life and low levels in breast milk. It
is also acceptable to give to infants. There are reports of
sedation.
Alprazolam: One case reported of withdrawal from alprazolam when
medication was tapered.
ADHD Treatments Guanfacine has no data on serum levels or safety,
but may lower prolactin Strattera has no published data Clonidine:
infant levels ranged from undetectable to 66% of maternal levels.
There
have been several reports of infants without adverse effects, but
one report of an infant with hypotonia, seizures and apnea that
resolved 24 hours after breastfeeding was stopped. Possible
galactorrhea. 57
Dextroamphetamine/amphetamine: found up to 15% serum levels in
infants. 4 cases published of mothers on 18-35mg daily where infant
developed normally without adverse events. Some data to show a non
statistical decrease in prolactin with IV amphetamines. Monitor for
agitation and poor weight gain. 58-59
Methylphenidate: 4 infants studied all (3 tested) had undetectable
methylphenidate levels and no adverse effects were reported.
Possible decrease prolactin levels. Monitor for agitation and poor
weight gain. 60
Cannabis Neurodevelopmental effects, delayed motor development at
1y, lethargy, less
frequent and shorter feeds, high milk-plasma ratio in heavy users
New study 61 on transfer of inhaled cannabis into human breast
milk. Looked at women who smoke cannabis regularly and are 2-5
months postpartum and
breast feeding. 8 moms where told not to smoke for 24 hours and
baseline levels where drawn. Then
they were told to smoke 3-4 hits of cannabis and breastmilk samples
were collected at 20 min, 1, 2 and 4 hours intervals afterwards and
THC was quantified by high performance liquid chromatography tandem
mass spectroscopy.
THC detected at low concentrations at all time points beyond
baseline. THC was transferred into mother’s milk such that
exclusively breastfeeding infants ingested estimated 2.5% of
maternal dose (range 0.4-8.7%)
Dysphoric milk ejection reflex (D- MER) Only recently described in
the literature, with 3 publications found on pubmed Websites, books
and blogs Negative feelings with each breastfeeding (milk let down)
episode. Described as
lasting 90-120 seconds with feeling worthless, poor concentration
(effecting math skills and reading skills), feeling homesick, and
feeling hollow.
Resolves after weaning. Speculation that it may involve oxytocin or
dopamine (dopamine could drop to
increase prolactin). In one case a woman reported that
pseudoephedrine was very helpful 67
Conclusion Breastfeeding has many health benefits to mother and
baby Traditional beliefs about breastfeeding and sleep are probably
incorrect Psychopharmacology during breastfeeding is challenging
due to limit data in most
agents, but with only rare exception it is not a reason to prevent
a mother from breastfeeding, albeit with close monitoring to the
infant in some cases Be sure about the diagnosis and severity of
symptoms Find out about what has worked in the past Avoid
polypharmacy whenever possible Coordinate with the
Pediatrician
Mother should be able to provide informed consent without a sense
of judgment from her physicians
Use your resources!
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Disclosures
Depressive Symptoms and Risk of Formula Feeding
Depression and Post Partum Sleep
How Do Babies Sleep?
Psychopharmacology and BF Safety
Insomnia
Anxiolytics
Conclusion
Questions?
References