Thursday, February 11, 2010

Psychiatric Medications - Effects on Breastfeeding

Fantastic compilation of what psych drugs can do to our babies and how much gets in our breastmilk by Dr. Richard Oliva at UCSF.



Summary of Data published on LactMed (http://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?LACT) as of 02/01/10
Drug
Into Breastmilk?
Effect on Infant/Safety/ Summary
Fluoxetine
The average amount of drug in breastmilk is higher with fluoxetine than with most other SSRIs and the long-acting, active metabolite, norfluoxetine, is detectable in the serum of most breastfed infants during the first 2 months postpartum and in a few thereafter.
Adverse effects such as colic, fussiness, and drowsiness have been reported in some breastfed infants. Decreased infant weight gain was found in one study, but not in others. No adverse effects on development have been found in a few infants followed for up to a year. If fluoxetine is required by the mother, it is not a reason to discontinue breastfeeding. If the mother was taking fluoxetine during pregnancy or if other antidepressants have been ineffective, most experts recommend against changing medications during breastfeeding.
Paroxetine
Because of the low levels of paroxetine in breastmilk, amounts ingested by the infant are small and paroxetine has not been detected in the serum of most infants tested.
Occasional mild side effects (alertness, constipation, sleepiness and irritability) have been reported, especially in the infants of mothers who took paroxetine during the third trimester of pregnancy, but the contribution of the drug in breastmilk is not clear. Most authoritative reviewers consider paroxetine one of the preferred antidepressants during breastfeeding.
Sertraline
Because of the low levels of sertraline in breastmilk, amounts ingested by the infant are small and is usually not detected in the serum of the infant, although the weakly active metabolite desmethylsertraline is often detectable in low levels in infant serum.
Most authoritative reviewers consider sertraline one of the preferred antidepressants during breastfeeding.
Citalopram
Infants receive citalopram in breastmilk and it is detectable in low levels in the serum of some. The dosage that the infant receives and serum level achieved are probably related to the genetic metabolic capacity of the mother and infant.
A few cases of minor behavioral side effects such as drowsiness or fussiness have been reported, but no adverse effects on development have been found in infants followed for up to a year. If citalopram is required by the mother, it is not a reason to discontinue breastfeeding. If the mother was taking citalopram during pregnancy or if other antidepressants have been ineffective, most experts recommend against changing medications during breastfeeding.
Escitalopram
Limited information indicates that maternal doses of escitalopram up to 20 mg daily produce low levels in milk and would not be expected to cause any adverse effects in breastfed infants, especially if the infant is older than 2 months.
Based on limited data, escitalopram appears to be preferable to racemic citalopram during breastfeeding because of the lower dosage and milk levels and general lack of adverse reactions in breastfed infants. Monitor the infant for drowsiness, especially in younger, exclusively breastfed infants and when using combinations of psychotropic drugs.
Bupropion
Limited information indicates that maternal bupropion doses of up to 300 mg daily produce low levels in breastmilk and would not be expected to cause any adverse effects in breastfed infants.
There is little reported use in breastfed newborn infants and one case report of a possible seizure in a partially breastfed 6-month-old. If bupropion is required by a nursing mother, it is not a reason to discontinue breastfeeding. However, another drug may be preferred, especially while nursing a newborn or preterm infant. Exclusively breastfed infants should be monitored if this drug is used during lactation, possibly including measurement of serum levels to rule out toxicity if there is a concern.
Duloxetine
No published information is available on the use of duloxetine during breastfeeding; however, the dose in milk is low.
An alternate drug that has been better studied may be preferred, especially while nursing a newborn or preterm infant. If duloxetine is required by the mother, it is not a reason to discontinue breastfeeding. Monitor the infant for drowsiness, adequate weight gain, and developmental milestones, especially in younger, exclusively breastfed infants and when using combinations of psychotropic drugs.
Venlafaxine
Infants receive venlafaxine and its active metabolite in breastmilk, and the metabolite of the drug can be found in the plasma of most breastfed infants, but no proven drug-related side effects have been reported.
Breastfed infants, especially newborn or preterm infants, should be monitored for excessive sedation and adequate weight gain if this drug is used during lactation, possibly including measurement of serum levels of desvenlafaxine [O-desmethylvenlafaxine], to rule out toxicity if there is a concern. However, newborn infants of mothers who took the drug during pregnancy may experience poor neonatal adaptation syndrome as seen with other antidepressants such as SSRIs or SNRIs. Use of venlafaxine during breastfeeding has been proposed as a method of mitigating infant venlafaxine withdrawal symptoms,[1] but only one apparently successful case of this use has been reported.
Desvenlafaxine
Although no data are available for the use of desvenlafaxine during breastfeeding, it is the active metabolite of venlafaxine. Venlafaxine study data indicate that relatively large amounts of desvenlafaxine are likely to be excreted into breastmilk.
Other agents may be preferred, especially while nursing a newborn or preterm infant. Breastfed infants should be monitored for excessive sedation and adequate weight gain if this drug is used during lactation, possibly including measurement of serum levels of desvenlafaxine to rule out toxicity if there is a concern. Because desvenlafaxine is available only as a sustained-release product, timing of nursing with respect to doses would not be useful.
Lithium
Random milk levels have been reported to range from 0.12 to 0.7 mEq/L and appear to be rather consistent at about 40 to 45% of the simultaneous maternal serum level.
Limited data suggest that lithium in milk can adversely affect the infant when its elimination is impaired, as in dehydration or in newborn or premature infants. Neonates may also have transplacentally acquired serum lithium levels. The long-term effects of lithium on infants are not known, but limited data indicate no obvious problems in growth and development. Although lithium appears on many lists of drugs contraindicated during breastfeeding, other sources do not consider it a contraindication, especially in infants over 2 months of age and during lithium monotherapy. Lithium may be used in mothers of full-term infants who are willing and able to monitor their infants. Some investigators recommend monitoring infant serum lithium, serum creatinine, BUN, and TSH every 4 to 12 weeks during breastfeeding and maternal lithium therapy.[2][3] Breastfeeding should be discontinued immediately if the infant appears restless or looks ill.
Valproic Acid
Because of the low levels of valproic acid in breastmilk and infant serum, no unquestionable adverse reactions to valproic acid during breastfeeding have been reported.
Theoretically, breastfed infants are at risk for valproic acid-induced hepatotoxicity, so infants should be monitored for jaundice and other signs of liver damage during maternal therapy. A questionable case of thrombocytopenia has been reported, so monitor the infant for unusual bruising or bleeding. One author recommends monitoring infant serum valproate levels, platelets and liver enzymes during therapy. Combination therapy with sedating anticonvulsants or psychotropics may result in infant sedation or withdrawal reactions.
Carbamazepine
Carbamazepine has relatively high levels in breastmilk and breastfed infants have serum levels that are measurable, but usually below the anticonvulsant therapeutic range.
Most infants have had no adverse reactions, but sedation, poor sucking, withdrawal reactions and 3 cases of hepatic dysfunction have been reported. These have all been complicated because of intrauterine exposure and, in some cases, concurrent drug therapy. If carbamazepine is required by the mother, it is not a reason to discontinue breastfeeding. Monitor the infant for jaundice, drowsiness, adequate weight gain, and developmental milestones, especially in younger, exclusively breastfed infants and when using combinations of anticonvulsant or psychotropic drugs.
Oxcarbazepine
The relationship of the maternal dosage to the concentration in breastmilk can be quite variable, making calculation of the weight-adjusted percentage of maternal dosage less meaningful than usual.
Limited information indicates that oxcarbazepine would not be expected to cause any adverse effects in breastfed infants, especially if the infant is older than 2 months. Monitor the infant for drowsiness, adequate weight gain, and developmental milestones, especially in younger, exclusively breastfed infants and when using combinations of anticonvulsants.
Lamotrigine
Breastfed infants whose mothers are taking lamotrigine have relatively high plasma lamotrigine levels, averaging 30 to 35% of maternal serum levels; infant plasma levels up to 50% of maternal levels have been reported. Neonates are particularly at risk for high plasma levels because their ability to metabolize the drug by glucuronidation is limited and maternal plasma and milk levels can rise dramatically in the immediate postpartum period if the dosage is not reduced to the prepregnancy dosage.
Additionally, lamotrigine can cause rare, but potentially fatal skin reactions. If lamotrigine is required by the mother, it is not necessarily a reason to discontinue breastfeeding, because many infants have been breastfed without adverse reactions. However, breastfed infants should be carefully monitored for side effects such as rash, drowsiness or poor sucking, including measurement of serum levels to rule out toxicity if there is a concern. If an infant rash occurs, breastfeeding should be discontinued until the cause can be established.
Gabapentin
Limited information indicates that maternal doses of gabapentin up to 2.1 grams daily produce relatively low levels in infant serum.
Monitor the infant for drowsiness, adequate weight gain, and developmental milestones, especially in younger, exclusively breastfed infants and when using combinations of anticonvulsant or psychotropic drugs.
Haloperidol
Limited information indicates that maternal doses of haloperidol up to 10 mg daily produce low levels in milk and do not affect the breastfed infant.
Very limited long-term follow-up data indicate no adverse developmental effects when haloperidol is used alone. However, combinations of antipsychotic agents can negatively affect development. Monitor the infant for developmental milestones, especially if other antipsychotics are used concurrently. In a small prospective study on the long-term effects of antipsychotics in breastfed infants, a decline in developmental scores was found at 12 to 18 months of age in 2 of the 4 the infants of mothers taking both chlorpromazine and haloperidol. The other 2 infants and all infants exposed to either drug alone developed normally.
Risperidone
Limited information indicates that maternal risperidone doses of up to 6 mg daily produce low levels in milk.
Because there is little published experience with risperidone during breastfeeding and few long-term follow-up data, other agents may be preferred, especially while nursing a newborn or preterm infant.
Olanzapine
Limited information indicates that maternal doses of olanzapine up to 20 mg daily produce low levels in milk and undetectectable levels in the serum of breastfed infants.
In most cases, short-term side effects have not been reported, but sedation has occurred. Very limited long-term follow-up of infants exposed to olanzapine indicates that infants generally developed normally, but combinations of antipsychotic agents can negatively affect development. Monitor the infant for drowsiness and developmental milestones, especially if other antipsychotics are used concurrently.
Quetiapine
Limited information indicates that maternal quetiapine oral doses of up to 400 mg daily produce low levels in milk. A 3-month-old infant who was breastfed 6 to 7 times daily during maternal use of 400 mg daily of quetiapine had a plasma quetiapine level of 1.4 mcg/L. This level was 6% of the mother's quetiapine plasma level at the same time.
Because there is little published experience with quetiapine during breastfeeding and little long-term follow-up data, other agents may be preferred, especially while nursing a newborn or preterm infant.
Clozapine
A woman taking oral clozapine 50 mg daily had a milk clozapine level of 63.5 mcg/L one day postpartum. At 3 days postpartum her dose was increased to 100 mg daily, and at 7 days postpartum clozapine in milk was 115.6 mcg/L. Her infant was not breastfed and timing of the samples with respect to the doses was not stated.
Because there is little published experience with clozapine during breastfeeding, and sedation and adverse hematologic effects have been reported in breastfed infants, other agents are preferred. If breastfeeding is undertaken by a mother who is taking clozapine, close monitoring of the infant for excessive sedation and periodic monitoring of the infant's white blood cell count is advisable.
Aripirazole
A women who was 6 months postpartum was taking aripiprazole 15 mg by mouth daily. Milk levels after 11 and 12 days of therapy (times not stated) at that dose were 13 and 14 mcg/L.
Because there is little published experience with aripiprazole during breastfeeding, other antipsychotic agents are preferred.
Ziprazidone
Relevant published information was not found as of the revision date.
Because there is no published experience with ziprasidone during breastfeeding, other antipsychotic agents are preferred.
Clonazepam
A mother taking clonazepam 2 mg twice daily had several milk level measurements on days 2 to 4 postpartum. The highest milk level was 10.7 mcg/L 4 hours after a dose. The authors calculated that an exclusively breastfed infant would receive a maximum of 2.5% of the maternal weight-adjusted dosage of clonazepam.
Only a small number of cases of breastfeeding with clonazepam have been reported. If clonazepam is required by the mother, it is not a reason to discontinue breastfeeding. Monitor the infant for drowsiness, adequate weight gain, and developmental milestones, especially in younger, exclusively breastfed infants and when using combinations of psychotropic drugs. Monitoring of the infant's serum concentration may be indicated if excessive sedation occurs.
Diazepam
Diazepam is excreted into breastmilk and it and its active metabolite, nordiazepam, accumulate in the serum of breastfed infants with repeated doses. Because the half-life of diazepam and nordiazepam are long, timing breastfeeding with respect to the dose is of little or no benefit in reducing infant exposure.
Other agents are preferred, especially while nursing a newborn or preterm infant. After a single dose of diazepam, as for sedation before a procedure, there is usually no need to wait to resume breastfeeding, although with a newborn or preterm infant, a cautious approach would be to wait a period of 6 to 8 hours before resuming nursing.
Alprazolam
The authors calculated that an exclusively breastfed infant whose mother was taking alprazolam in the normal dosage range would receive a dose of 0.5 to 5 mcg/kg/day or about 3% of the maternal weight-adjusted dosage.
Because of reports of effects in infants, including sedation, alprazolam is probably not the best benzodiazepine for repeated use during nursing, especially with a neonate or premature infant. A shorter-acting benzodiazepine without active metabolites is preferred. After a single dose of alprazolam, there is usually no need to wait to resume breastfeeding.
Lorazepam
Lorazepam has low levels in breastmilk, a short half-life relative to many other benzodiazepines, and is administered directly to infants.
Lorazepam would not be expected to cause any adverse effects in breastfed infants with usual maternal dosages. No special precautions are required.
Trazodone
Trazodone levels in milk are low
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.
Clonidine
Using the average milk level data from this study, an exclusively breastfed infant would receive an estimated 4.1 to 8.4% of the maternal weight-adjusted dosage.
Because of the high serum levels found in breastfed infants and the possible negative effects on lactation, other agents may be preferred, especially while nursing a newborn or preterm infant. Clonidine has complex, dose-related actions on both oxytocin and prolactin secretion. The net effect of the drug on nursing mothers has not been well studied. A case of hyperprolactinemia and gynecomastia occurred in a 6-year-old boy taking clonidine for hyperactivity and valproic acid for a seizure disorder. Galactorrhea ceased within 3 weeks of discontinuing clonidine. A case of clonidine-induced postpartum galactorrhea has also been reported.
Prazosin
Relevant published information was not found as of the revision date.
Because no information is available on the use of prazosin during breastfeeding, an alternate drug may be preferred, especially while nursing a newborn or preterm infant.
Hydroxyzine
Relevant published information was not found as of the revision date.
Small occasional doses of hydroxyzine would not be expected to cause any adverse effects in breastfed infants. Larger doses or more prolonged use may cause drowsiness and other effects in the infant or decrease the milk supply, particularly in combination with a sympathomimetic or before lactation is well established. Single bedtime doses after the last feeding of the day may be adequate for many women and will minimize any effects of the drug. The nonsedating antihistamines are preferred alternatives.
Imipramine
Milk levels of imipramine and its metabolite are low and have been detected in only small quantities 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. Other agents may be preferred when large doses are required or while nursing a newborn or preterm infant.
Clomipramine
Using the average of the above concentrations, a fully breastfed infant would receive about 2.2% of the maternal weight-adjusted dosage of clomipramine in breastmilk.
Limited evidence indicates that use of clomipramine during breastfeeding is acceptable. For use as an antidepressant, clomipramine may be less desirable than other tricyclic antidepressants that have been studied more thoroughly.
Nortriptyline
Because of the low levels of nortriptyline in breastmilk, amounts ingested by the infant are small and usually not been detected in the serum of the infant, although the less active metabolites are often detectable in low levels in infant serum.
Immediate side effects have not been reported and a limited amount of follow-up has found no adverse effects on infant growth and development. Most authoritative reviewers consider nortriptyline one of the preferred antidepressants during breastfeeding.

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