It is estimated that up to 95% of women experience some type of sleep disturbance during pregnancy.  While for many women the insomnia is relatively benign and may respond to simple interventions, other women experience more severe insomnia which has a significant impact on their quality of life and ability to function.  Trazodone (Desyrel) is FDA-approved for the treatment of major depressive disorder; however, because it is highly sedating, it is more commonly used to promote sleep.  However, information regarding the reproductive safety of these medications has been relatively sparse.

Insomnia, especially when severe, may be associated with worse pregnancy outcomes and may increase risk for depression during pregnancy and the postpartum period.  The treatment of insomnia involves understanding of the underlying causes of insomnia and choosing medications which target the causes of insomnia. For example, if insomnia appears to be related to untreated anxiety, one might select treatments that target anxiety, including cognitive-behavioral therapy for anxiety, SSRI and SNRI antidepressants, and benzodiazepines.

The following is a review of the use of trazodone during pregnancy. The information is covered in the slideshow below the text. 

Trazodone (Desyrel)

  • FDA-approved for the treatment of MDD
  • More commonly used to promote sleep

Sleep Disorders During Pregnancy

Sleep problems are common during pregnancy

  • Sleep increases in the 1st trimester, decreases in the 3rd trimester
  • Sleep disturbance is common: 13% in the first trimester, 19% in the 2nd, 66% in the 3rd
  • Up to 73.5% of women report insomnia: mild 50.5%, moderate 15.7%, and severe 3.8%

What causes insomnia during pregnancy?

  • Pregnancy-associated symptoms: urinary frequency, heartburn, fetal movements
  • Sleep apnea (up to 26% in 3rd trimester)
  • Restless leg syndrome
  • Anxiety
  • Depression

Should insomnia during pregnancy be treated?

Untreated insomnia during pregnancy

Other negative effects of insomnia during pregnancy

  • Increased activity of HPA axis, inflammation
  • Increased risk of gestational diabetes
  • Increased risk of C-section
  • Preterm birth, lower birth weight

Risk of Major Malformations – Two Studies

Einarson et al (2003)

  • 58 exposures, 2 malformations

Einarson et al (2009)

  • 17 exposures, no malformations

Limitations of studies (less than 100)

  • Inadequate number of exposures 
  • Many women using other medications

Alternative Treatments

  • Cognitive behavioral therapy for insomnia
  • Doxylamine (in Diclegis and Unisom)
  • Benzodiazepines – More data to support reproductive safety
  • SSRIs and SNRIs for treatment of anxiety, depression
  • Tricyclic antidepressants – Sedating TCAs imipramine, amitriptyline at low doses.  Risk of hypotension.

Trazodone and Pregnancy Feb 2022 by Ruta Nonacs, MD PhD. Click to see full screen.

 

References

Dominguez JE, Street L, Louis J. Management of Obstructive Sleep Apnea in Pregnancy. Obstet Gynecol Clin North Am. 2018;45(2):233-247.

Einarson A, et al. 2003. A multicentre prospective controlled study to determine the safety of trazodone and nefazodone use during pregnancy. Can J Psychiatry 48(2):106-110.

Einarson A, et al. 2009. Incidence of major malformations in infants following antidepressant exposure in pregnancy: results of a large prospective cohort study. Can J Psychiatry 54(4):242 246.

Manber R, Bei B, Simpson N, Asarnow L, Rangel E, Sit A, Lyell D. Cognitive Behavioral Therapy for Prenatal Insomnia: A Randomized Controlled Trial. Obstet Gynecol. 2019 May;133(5):911-919. Free Article

Reichner CA. Insomnia and sleep deficiency in pregnancy. Obstet Med. 2015;8(4):168-171. https://doi.org/10.1177/1753495X15600572

Srivanitchapoom P, Pandey S, Hallett M. Restless legs syndrome and pregnancy: a review. Parkinsonism Relat Disord. 2014;20(7):716-722.

Silvestri, R. & Arico, I. Sleep disorders in pregnancy. Sleep Sci. 2019; 12: 232–239. https://doi.org/10.5935/1984-0063.20190098

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