Antidepressants, Antipsychotics, Benzodiazepines, and the Breastfeeding Dyad

Perspectives in Psychiatric Care, Apr-Jun 2004 by Malone, Kirsten J, Papagni, Karla, Ramini, Sasha, Keltner, Norman L

Olanzapine (Zyprexa). Olanzapine is similar to clozapine both in chemical structure and mechanism of action. Olanzapine is well absorbed but rapidly metabolized by first-pass effect, resulting in 60% bioavailability in the mother. It is 93% protein bound and has a half-life of 21 to 54 hours (Deglin & Vallerand, 2003).

One study (Gardiner et al., 2003) of six women with a median daily dose of 7.5 mg (range: 50 -0 20 mg) reported the median amount of olanzapine found in breast milk was 1.02% of the maternal dose. Infant serum levels of olanzapine were undetectable, and no adverse effects were reported. The median M/P ratio was 0.38. The data acquired about the usage of olanzapine while breastfeeding indicate it may be considered relatively safe when nursing healthy, full-term infants.

Risperidone (Risperdal). Risperidone has a half-life of 3 hours and is 88% protein bound. It is 70% absorbed by the mother and extensively metabolized by the liver (Deglin & Vallerand, 2003). Its metabolite, 9-hydroxyrisperidone, is active, and both drug and metabolite are found in breast milk. 9-hydroxyrisperidone has a half-life of 21 hours (Deglin & Vallerand, 2003; Keltner, 1995).

Data concerning risperidone and breastfeeding are very limited. One case study was conducted with a 21-year-old woman with a history of bipolar disorder. Her daily dose of risperidone was 6 mg. After 1 week of medication, the mother provided seven serial samples of serum and six serial samples of breast milk every 4 hours over 24 hours. The M/P ratios of risperidone and 9-hydroxyrisperidone were 0.42 and 0.24, respectively. It was calculated that the infant received 4.3% of the maternal dose, adjusted for weight (Hill et al., 2000). Hill and colleagues recommended either discontinuation of drug or cessation of breastfeeding while taking risperidone, due to the unknown short-term and long-term effects on breast-fed infants. However, this is a conservative recommendation as this is a single case report, and no adverse effects were reported in the infant. Hale (2002) classifies risperidone as "moderately safe," indicating the drug should be given while breastfeeding continues only if potential benefits justify the risk to the infant.

Benzodiazepines

Benzodiazepines are used frequently in postpartum women to control anxiety, panic disorder, and seizures. The risk of breastfeeding while using those drugs remains a topic that is controversial and underresearched. The AAP (2001) categorizes benzodiazepines as "drugs for which the effect on nursing infants is unknown, but may be of concern" (p. 776). Even though the guidelines do not preclude the use of benzodiazepines in women who breastfeed, many postpartum women are routinely counseled not to nurse their infants.

Benzodiazepine withdrawal syndrome was described in infants who were chronically exposed to benzodiazepines in utero, and floppy infant syndrome has been documented in newborns exposed to benzodiazepines during labor (Mortola, 1989). Even though a scattering of studies report drowsiness and decreased sucking reflex in infants exposed to benzodiazepines through breast milk (Suri, Altshuler, Burt, & Hendrick, 1998), it is important to keep in mind that all infants studied were also exposed in utero.