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Bupropion

A case report describes bupropion (= amfebutamon- half-life 21 hours), a drug with a serotonin, noradrenaline, and dopamine blocking action, which is also used for weaning from cigarette smoking. An M/P ratio of up to 8, and a relative dosage (including the 50% effective metabolites erythrohydrobupropion, hydroxy-bupropion, and thre-ohydrobupropion) of less than 1% on average and 3% at maximum, have been calculated (Weissman 2004). Neither in this nor in two other cases was the drug detected in the infant's serum (Baab 2002). A more recent study of 10 mothers receiving 150 mg/d for 3 days and then 300 mg/d for 4 days calculated, on average, 6.75(i.g/kg per day bupropion plus 10.8, 15.75, and 68.9pg/kg per day of the respective metabolites (see above) for a fully breastfed child. Considering bupropion only, the relative dose is 0.14%; including its metabolites, this is about 2% (Haas 2004).

Hypericin (St John's wort)

St John's wort or hypericin preparations can inhibit prolactin secretion. Therefore, they have the potential to reduce milk production (Franklin 1999). Traces of hyperforin were found in the milk of a mother on long-term therapy of 900 mg/d; hypericin, however, was not detectable (detection limit <0.2ng/ml). There was no drug in the infant's serum (Klier 2006). Based on five mothers taking a similar dose, an M/P ratio of 0.04-0.3 and a relative dosage of 0.9-2.5% were calculated. In the blood of two of the children the substance was measured at the detection limit (O.lng/mt). Another study involving 33 mother-child pairs observed moderate symptoms, such as colic and lethargy, in 5 of the exposed infants. Although the number of symptomatic children was significantly higher than in the two control groups, no child required therapy. The authors could not exclude additional psychotropic drugs as a confounding factor (Lee 2003). The weight gain of these children was not compromised, and neither was the milk production. This speaks against a clinically relevant inhibitory effect on prolactin.

Mirtazapine

Mirtazapine has a protein binding of 85% and a half-life of 20-40 hours. Three weeks after delivery, a mother was switched from sertraline to mirtazapine 30mg/d. After reaching steady state, a level of 2.5 |ig/l was measured in her serum; 34 i>g/l was the peak value in the milk, and 0.2|ig/l was found in the infant's serum. A relative dose of up to 1% was calculated. The breastfed child was normally developed at the age of 6 weeks (Aichhorn 2004).

Modobemide

The reversible MAO inhibitor moclobemide was studied in six mother-child pairs. An M/P ratio of 0.7 and a relative dosage of 1.2% were reported (Pons 1990).

Nefazodone, a 5-HT2-receptor antagonist, was studied in three samples with two patients. With a daily dosage of between 100 and 400 mg, concentrations of the active ingredient, including the active metabolite hydroxynefazodone, of 57-700 pg/1 were found in the milk. However, the sampling was done before the patients took the tablets (two single doses daily). The patients had been in treatment for at least 3 weeks (Dodd 1999). From these measurements, a relative dosage of between <1% and 7% can be calculated for the fully breastfed baby. A further case report describes a premature infant who. mathematically, received only 0.5% of the weight-related maternal dosage (daily dosage 300 mg), and still had to be hospitalized because of lethargy, weak suck, and problems with temperature regulation. These symptoms improved within 72 hours after weaning (Yapp 2000).

Among six women who took single doses of 50 mg of trazodone, an M/P ratio of 0.14 and a child's dosage of 15 jig/kg trazodone daily were calculated. This represents just under 2% of the weight-related dosage. I lowever, it should be noted that the pharmacologically active metabolite 1-m-chlorophenylpiperazine was not included in the calculations (Verbeek 1986).

The half-life of venlafaxine, a serotonin and noradrenaline reuptake inhibitor, is 26 hours. Based on eight mother-child pairs, an M/P ratio of about 4 was reported. When the active metabolite O-desrnethyl-venlajaxine is included the breastfed baby receives on average 6% (a maximum of 9%) of the maternal weight-related dosage. The metabolite, but not venlafaxine itself, was measured at levels of 3-38|tg/l in the scrum of the breastfed infants, who developed uneventfully. These serum values correspond to 10% of the maternal concentrations (Berle 2004, Weissman 2004, llett 2002, Hendrick 2001B).

There are either no or insufficient data on the use of amineptine, amoxapine, atomoxetine, duloxetine, iprindole, medifoxamine, oxitrip-tan, reboxetine, tranylcypromine, I,-tryptophan, and viloxazine during breastfeeding.

Recommendation. Due to the quantity and the results of documented experience, St. John's wort or hypericin preparations and mirtazapine are acceptable during breastfeeding, If compellingly indicated, moclobemid, venlafaxine, and bupropion are also tolerable. Whenever possible, the drugs of choice among tricyclic antidepressants or SSRIs are preferable. In general, monotherapy should be the goal. In cases of symptoms potentially associated with the drug therapy, a pediatrician and a teratology information center should be contacted to decide individually upon measuring drug values in the infant's serum, supplementary formula feeding, weaning, and/or changing the therapy. As with all psychoactive drugs, there is insufficient experience on the long-term effects on breastfed children of ongoing maternal therapy.

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