Research Article

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Low Dose of Abilify (Aripiprazole) in Combination With Effexor XR (Venlafaxine HCl) Resulted in Cessation of Lactation

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Abstract

Postpartum depression (PPD) is a relatively common experience for women, especially those who have a history of preconception and/or prenatal depression. In some cases, pharmaceutical treatment is required to treat the symptoms of PPD. Unfortunately, the use of some of these treatments may have unintended consequences that affect both the newborn and the new mother. Here we report a case where Abilify (aripiprazole) at a low dose (2 mg/day) was prescribed in conjunction with Effexor XR (venlafaxine HCl) at a high dose (225 mg/day), which resulted in the cessation of lactation.

Scope of the Problem

In the United States, one in nine women will experience postpartum depression (PPD). However, this number is likely to be much higher because of underreporting (Centers for Disease Control and Prevention, 2017). This number significantly increases in those who have a predisposition, specifically for women with preconception and prenatal depression (Beck, 2001; Byatt et al., 2014; Chittleborough, Lawlor, & Lynch, 2012; Dietz et al., 2007). In a study by Ko, Farr, Dietz, and Robbins (2012), diagnosis of depression led to treatment in only 54% of nonpregnant and 50% of pregnant women, with prescription medication as the primary means of treatment for all study participants at 47% and 40%, respectively. In comparison to PPD, Price, Corder-Mabe, and Austin (2012) found that only 52% of healthcare providers treat or refer patients with PPD, where 75% of cases were prescribed medication. There is scant information available in the literature regarding the newer atypical/second-generation antipsychotics and their effects during pregnancy and lactation (Frew, 2015; LactMed, 2018a). The lack of information about treatment options leaves many women with unanswered questions about the unintended consequences of those treatments.

Breastfeeding provides many benefits to a mother, including reducing the risk of PPD (Gregory, Butz, Ghazarian, Gross, & Johnson, 2015; Ip, Chung, Raman, Trikalinos, & Lau, 2009). Unfortunately, many mothers are unable to breastfeed for the length of time that they would like. Stuebe et al. (2014) found that over 50% of women who reported a desire to breastfeed had early, undesired weaning. Additionally, one in eight women had this undesired weaning linked to disrupted lactation (Stuebe et al., 2014). Stuebe, Grewen, Pedersen, Propper, and Meltzer-Brody (2012) initially linked failed lactation and perinatal depression. Further investigation by Stuebe et al. (2014) found a correlation between maternal depression and disrupted lactation, meaning that mothers who suffered from depression were more likely to have undesired weaning due to lactation issues.

For mothers with PPD who want to breastfeed, prescription medication options that lead to cessation of breast milk production are an unwanted consequence. Venlafaxine is a prescription medication commonly prescribed in dosages ranging from 37.5 mg to 375 mg daily for depression in women, and its associated risk factors during pregnancy and with breastfeeding postpartum have been thoroughly monitored since 1998 (LactMed, 2018b). Aripiprazole is a newer medication, monitored since 2007, for treatment of depression in women at levels of up to 15 mg/day (LactMed, 2018a). In high doses of 17.3 mg/day on average, aripiprazole was found to cause hypoprolactinemia (prolactin deficiency) at a rate of 81% (Lozano, Marin, & Santacruz, 2014). However, aripiprazole at 5 mg/day has been used to treat hyperprolactinemia (prolactin surplus), which is a common side effect of other antipsychotic drugs (Li, Tang, & Wang, 2013). In 2015, the first report of lactation interruption associated with the use of a low dose of aripiprazole (2.5 mg/day) was presented (Frew, 2015). Therefore, a careful assessment of risks of use of aripiprazole should be thoroughly discussed with patients before a treatment is started.

Case Study

We present a case where the low dosage of aripiprazole (2 mg/day), also known as Abilify, was used, but in conjunction with daily use of venlafaxine HCl, also known as Effexor XR (225 mg/day), where lactation ceased in a 31-year-old primigravid female. After consultation with the chairperson of the Human Subjects Review Committee at Gordon State College (GSC), it was determined that institutional review board (IRB) approval from GSC was not required for this report. The patient has given complete consent for this to be published and has reviewed the manuscript.

Prior to the patient's pregnancy, she had been successfully treated for anxiety and depression with acombination of 2 mg aripiprazole and 225 mg venlafaxine HCl daily. Approximately 6 weeks into the pregnancy, the aripiprazole was discontinued at the advice of the patient's primary care physician because of concerns about potential harm to the fetus, but the venlafaxine HCl was continued at the same dose throughout the pregnancy. The pregnancy produced a healthy infant at 36.5 weeks; an emergency cesarean section was performed because the patient was suffering from preeclampsia. In the hospital, at the advice of the nurses, the patient began pumping after every attempted feeding, which occurred every 2–3 hours, because of perceived poor colostrum production. At 3 days postpartum, lactogenesis II began and the infant was fed from each breast for 15–30 minutes every 2–3 hours. The patient knew that lactogenesis II began because of fullness in the breasts. Feedings were followed by pumping until all the milk was expressed from each breast. This was done due to a maternal desire to store expressed breast milk for future use.

At 6 days postpartum, the infant had a pediatrician's appointment where it was discovered that he had lost 12 oz (∼9% of his body mass). The pediatrician instructed the mother to supplement the infant with 2.5 oz of expressed breast milk or formula by bottle after all breastfeeding sessions due to suspected poor milk transfer from the breast. The patient continued to feed the infant every 2–3 hours and followed each feeding with a pumping session that emptied each breast of milk. Typically a total of 5–6 oz of milk was expressed from both breasts after these attempted feedings (therefore total milk output was estimated to be at least 30 oz/24 hours). This additional milk was stored for supplementation as directed by the pediatrician.

Unfortunately, the patient began to experience symptoms of PPD within 8 days postpartum. She returned to her primary care physician for treatment. The primary care physician recommended that the patient resume her prepregnancy treatment regime of 2 mg aripiprazole, in addition to the 225 mg venlafaxine HCl that she was already taking daily.

Approximately 3 days after the treatment with aripiprazole began, the patient noticed a decline in milk production in terms of the amount of milk expressed in the postfeeding pumping sessions. The patient consulted an IBCLC, who came to her home and assessed the situation. The IBCLC observed that the infant was latching properly, but that his suckling alternated between nutritive and nonnutritive patterns. The IBCLC recommended that the patient use manual breast compressions to increase milk output during both feeding and postfeeding pumping sessions. Despite these interventions, the patient's milk supply decreased to less than 1 oz total from both breasts in the postfeeding pumping sessions by 15 days postpartum. Within 21 days postpartum, lactation had ceased and the patient could no longer express milk using breast compressions or with a pump and breast compressions. No further follow-up with the IBCLC was performed. The infant was transitioned to an exclusively formula-based diet and thrived.

Conclusion

Clinicians and IBCLCs should be made aware that even at low dosages (2 mg/day), aripiprazole may affect lactation. If clinicians encounter a mother who is taking aripiprazole, they should work with an IBCLC to monitor the milk supply of the mother and have an alternative feeding plan prepared for the infant if lactation is negatively affected. If the mother wants to breastfeed, alternative treatment plans for PPD, which may include other pharmaceutical agents and therapy, should be available to reduce the negative effects that aripiprazole may have on lactation. If aripiprazole is the best treatment option for the mother, then she should be informed that one of the side effects may be cessation of lactation. An alternative to breastfeeding needs should be discussed early with a plan in place to ensure optimal health of the infant. Lactation failure, as seen in this case, could have resulted in the dehydration and accidental starvation of the infant if medical intervention had not been sought at regular intervals and an IBCLC consulted early on.

While there is evidence that breastfeeding can reduce the risk of PPD (Figueiredo, Canário, & Field, 2014), the intention of breastfeeding and its subsequent failure can actually increase the risk of PPD (Borra, Iacovou, & Sevilla, 2015). Unfortunately, maternal postnatal depression can increase the likelihood that lactation will be disrupted and breastfeeding may be more difficult (Stuebe et al., 2014). Hence clinicians may want to control depressive symptoms pharmacologically to prolong the lactation period. The choice of drugs must be carefully considered, as some pharmacological agents may be directly linked to failed lactation (Stuebe et al., 2012). Therefore, we suggest further research be performed examining the effects of low doses (<5 mg/day, as defined by Li et al. [2013]) of aripiprazole alone and in combination with other antipsychotics/antidepressants to understand how it may affect the milk supply in mothers who desire to breastfeed their infants.

References

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Disclosure

The authors have no relevant financial interest or affiliations with any commercial interests related to the subjects discussed within this article.

Acknowledgment

The authors would like to thank Marsha Walker and two anonymous reviewers for their comments on this manuscript. Their comments and suggestions greatly improved its quality.

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