Modafinil (brand name Provigil) is a wake-promoting agent which is used to treat sleepiness due to narcolepsy, shift work sleep disorder, or obstructive sleep apnea.  It is also used to in others settings, often in combination with other medications, to treat ADHD symptoms, depressive symptoms, and cognitive dysfunction.  

A research letter from Denmark published this week in JAMA Psychiatry raises concerns regarding the use of modafinil during pregnancy.  

Using Danish healthcare registries, researchers compared the outcomes of pregnancies in which women received prescriptions for modafinil during the first trimester (n=50) or the stimulant methylphenidate (n=960),  to pregnancy outcomes in nearly 830,000 unexposed pregnancies.

Major congenital malformations were identified in 12% of modafinil-exposed pregnancies, 4.5% of methylphenidate-exposed pregnancies, and 3.9% of unexposed pregnancies. After adjusting for potential confounders, modafinil was associated with a significantly increased risk for malformation compared to methylphenidate or no exposure.

This is a preliminary study, which included only 50 modafinil-exposed infants; however, there is a clear increase in risk for malformations in women using modafinil.  Other factors may be contributing to this increase in risk, but until we obtain more data, we would avoid, if possible, the use of modafinil in women who are either pregnant or planning to conceive. 

Health Canada has issued the following recommendations:   

  • Women who are pregnant, or plan to become pregnant, should not use modafinil.
  • Because hormonal birth control methods, such as birth control pills, may not work as well when used at the same time as modafinil, women using these types of birth control may have a higher chance of getting pregnant while taking modafinil. Alternative modes of birth control should be considered.  
  • Women should take a pregnancy test within a week before starting treatment with modafinil to ensure they are not pregnant.

As far as I know, the FDA has not issued a specific warning regarding the use of modafinil during pregnancy.  

There is a registry for women who become pregnant during treatment with PROVIGIL. The purpose of this registry is to collect information about the safety of PROVIGIL during pregnancy. Patients and their providers can get information and enroll in the registry by calling 1-866-404-4106.

Ruta Nonacs, MD PhD

Damkier P, Broe A.  First-Trimester Pregnancy Exposure to Modafinil and Risk of Congenital Malformations.  JAMA Psychiatry, January 2020.