The Impact of Modafinil on Pregnancy Outcomes
Modafinil, commonly prescribed for conditions like narcolepsy, shift work sleep disorder, and obstructive sleep apnea, has raised concerns about its safety during pregnancy. Emerging research and regulatory advisories increasingly highlight potential risks associated with modafinil exposure in pregnant women, particularly regarding congenital malformations and fetal growth.
Modafinil: Usage and Pregnancy Safety Concerns
Modafinil is a wakefulness-promoting agent primarily used to treat excessive daytime sleepiness in narcolepsy, obstructive sleep apnea, and shift work disorder. However, its safety profile in pregnancy remains concerning due to emerging evidence of adverse fetal outcomes.
A Danish national cohort study found that first-trimester exposure to modafinil was associated with a significantly increased risk of major congenital malformations compared to unexposed pregnancies (Damkier & Broe, 2020). Similarly, data from the US Provigil/Nuvigil Pregnancy Registry revealed a 13% prevalence of major congenital malformations among exposed live births, notably cardiac defects and hypospadias, compared with approximately 3% in the general population (Kaplan et al., 2021).
Insights from Recent Studies and Registries
Risk of Congenital Malformations
- The Danish registry-based study (49 modafinil-exposed pregnancies) documented a higher incidence of birth defects relative to matched controls, underscoring safety concerns with first-trimester exposure (Damkier & Broe, 2020).
- The US pregnancy registry (148 pregnancies) reported a 13% rate of major malformations, including heart defects and hypospadias, confirming the signal of teratogenicity in humans (Kaplan et al., 2021).
- Conversely, a large European multicenter case series (175 exposed pregnancies) did not find a statistically increased risk of major congenital anomalies but noted a tendency toward lower birth weights and smaller head circumferences, suggesting potential growth effects needing further evaluation (Onken et al., 2024).
Fetal Growth and Neonatal Outcomes
The European case series suggested a dose-dependent reduction in birth weight and head circumference in newborns exposed to modafinil, although clinical relevance remains uncertain and confounding factors may influence these findings (Onken et al., 2024).
Regulatory Responses and Clinical Recommendations
Regulatory agencies, including the US FDA and European Medicines Agency (EMA), have issued warnings against the use of modafinil during pregnancy due to potential fetal harm. The FDA label specifically notes that animal studies indicate risk of fetal harm and recommends effective contraception during treatment, continuing for one month after discontinuation of modafinil (U.S. Food and Drug Administration, 2015).
Healthcare providers are advised to:
- Avoid prescribing modafinil to pregnant women or those planning pregnancy.
- Counsel women of childbearing potential on risks and contraception options.
- Consider safer alternative therapies or behavioral strategies for managing narcolepsy and related disorders during pregnancy.
Alternative Treatment Options and Precautionary Measures
Non-pharmacologic approaches, such as improving sleep hygiene, scheduled naps, and lifestyle modifications, may be effective for some patients. When medication is necessary, clinicians should preferentially select agents with better-established safety profiles during pregnancy.
Women taking modafinil should be informed of the importance of effective contraception to prevent unplanned pregnancies. For those planning pregnancy, early consultation about discontinuing modafinil and switching treatments is essential.
The Role of Healthcare Providers
Clinicians play a crucial role in:
- Informing patients about the documented risks of modafinil during pregnancy.
- Ensuring pregnancy tests before initiation and ongoing monitoring during treatment.
- Reporting any adverse pregnancy outcomes related to modafinil to improve pharmacovigilance data.
- Supporting shared decision-making with patients balancing benefits and risks.
Conclusion
Modafinil offers substantial benefits for managing narcolepsy and related sleep disorders but carries significant risks for fetal development when used during pregnancy. Robust epidemiologic and registry data indicate an increased risk of congenital malformations and potential fetal growth impairment. As a result, health authorities recommend against modafinil use during pregnancy unless absolutely necessary and stress the importance of contraception for women of childbearing potential.
Careful counseling, alternative therapies, and vigilant monitoring are essential to optimize outcomes for both mother and child.
References
- Damkier, P., & Broe, A. (2020). First-trimester pregnancy exposure to modafinil and risk of congenital malformations. JAMA, 323(4), 374–376. https://doi.org/10.1001/jama.2019.20008
- Kaplan, S., Braverman, D. L., Frishman, I., & Bartov, N. (2021). Pregnancy and fetal outcomes following exposure to modafinil and armodafinil during pregnancy. JAMA Internal Medicine, 181(2), 275–277. https://doi.org/10.1001/jamainternmed.2020.4009
- Onken, M., Lohse, L., Coulm, B., Beghin, D., Richardson, J. L., Bermejo-Sánchez, E., Aguilera, C., Bosch, M., Cassina, M., Chouchana, L., De Santis, M., Duman, M. K., Gören, M. Z., Johnson, D., Bera, A. P. J., Kaplan, Y. C., Kennedy, D., Kwok, S., Lacroix, I., Lepelley, M., … Dathe, K. (2024). Effects of maternal modafinil treatment on fetal development and neonatal growth parameters—a multicenter case series of the European Network of Teratology Information Services (ENTIS). Acta Psychiatrica Scandinavica, 150(5), 372–384. https://doi.org/10.1111/acps.13643
- U.S. Food and Drug Administration. (2015). PROVIGIL® (modafinil) tablets, for oral use, C-IV [Prescribing information]. U.S. Department of Health and Human Services. https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/020717s037s038lbl.pdf
- Greenblatt, K., & Adams, N. (2023). Modafinil. In StatPearls [Internet]. StatPearls Publishing. https://www.ncbi.nlm.nih.gov/books/NBK531476/
