Narcolepsy in Pregnancy and Breastfeeding

Excessive daytime sleepiness is a cardinal sign of narcolepsy. While there are various well-studied drugs for treatment of narcolepsy, little is known in regards to treatment for narcolepsy during pregnancy or breastfeeding. Ultimately, the decision to treat is up to the informed patient.
 
In pregnancy, there are no adequate well-controlled studies done in pregnant women on stimulants used to treat narcolepsy. Thus, current recommendations are to discontinue any stimulants during pregnancy unless the risks of inadequate treatment outweigh the benefits to the fetus. (1) There is also an increased risk of cataplexy during delivery; elective cesarean section is advised. (2) If, treatment is absolutely necessary, sodium oxybate (Xyrem) is pregnancy category B and may provide a suitable choice. In animal studies with sodium oxybate, there have been no teratogenic effects reported. However, sedation is observed since it has been used as an anesthetic. Sodium oxybate is considered a controlled substance due to the potential for abuse. (3)
 
Other therapeutic agents used to treat narcolepsy in pregnancy that have been studied are amphetamines (Adderall) and modafinil (Provigil). Both are pregnancy category C. Amphetamine usage is the most studied, although the results are not reassuring. Amphetamines usage during pregnancy has been linked to prematurity, congenital malformations, and low birth-weight. (4,5,6) Withdrawal symptoms are observed after birth in neonates exposed to amphetamines: jitteriness, respiratory distress, drowsiness. (7) This data is currently inadequate however since the sample sizes are small and there was no accounting for bias. The National Toxicology Program states there is some concern for adverse developmental effects due to prenatal exposure to amphetamines. Modafinil has even less data, and has been reported to be linked to intrauterine growth retardation and spontaneous abortion in animal studies with ten-fold higher doses than normal human doses. (8)
 
Modafinil use in breastfeeding is not advised. There is no data available on its transfer to breast milk. However, it is likely to transfer due to the fact that it is small in molecular weight and lipid soluble. Also, there have been reports of dopamine stimulation by modafinil. Dopamine stimulation inhibits prolactin release, which may suppress milk production. (9)
 
A suitable alternative to treat narcolepsy during breastfeeding may be methylphenidate (Ritalin). Methylphenidate has a very small relative infant dose (0.2-0.4%), and transfer to human milk is minimal. No adverse effects have been found in infants exposed to methylphenidate during breastfeeding, which is reassuring. (9) Nevertheless, it is important to monitor carefully for reduced weight gain and agitation. The National Toxicology Program reports that there is negligible concern for methylphenidate-caused movement disorders.
 
References:
 
1. Hoque, R. and A. L. Chesson, Jr. (2008). "Conception, pregnancy, delivery, and breastfeeding in a narcoleptic patient with cataplexy." J Clin Sleep Med 4(6): 601-603.
2. Williams, S. F., J. R. Alvarez, et al. (2008). "Glutaric aciduria type II and narcolepsy in pregnancy." Obstet Gynecol 111(2 Pt 2): 522-524.
3. Pharmaceutical Manufacturers Prescribing Information 2009.
4. Gilbert EF and Khoury GH: Dextroamphetamine and congenital cardiac malformations. J Pediatr 76:638, 1970.
5. Matera RF et al: Bifid exencephalia. Teratogen action of amphetamine. Int Surg 50:79-85, 1968.
6. Little BB et al: Methamphetamine abuse during pregnancy: outcome and fetal effects. Obstet Gynecol 72:541-4, 1988.
7. Smith L, Yonekura ML, Wallace T, Berman N, Kuo J, Berkowitz C: Effects of prenatal methamphetamine exposure on fetal growth and drug withdrawal symptoms in infants born at term. J Dev Behav Pediatr 2003;24:17-23.
8. Pharmaceutical Manufacturers Prescribing Information 2008

9. Hale TW.  Medications and Mothers’ Milk.  Fourteenth Edition.  Hale Publishing LP, 2010  

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