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09. Consequences of Benzodiazepine Use in Pregnancy, Breastfeeding, and Adolescence

Published on May 1, 2024 Certification expiration date: May 1, 2027

Alexis Ritvo, M.D., M.P.H.

Addiction Psychiatry Fellowship Program director and assistant professor - University of Colorado School of Medicine

Key Points

  • When possible, avoid benzodiazepine use in pregnancy.
  • Encourage pregnant patients to taper off by the third trimester.
  • Be aware that benzodiazepines pass into the breast milk and pose a risk to the infant.
  • Utilize the shorter half-life benzodiazepines if they are required during pregnancy.
  • Benzodiazepine use should be avoided and, if necessary, used in a limited fashion in adolescents.

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Slides and Transcript

Slide 1 of 21

In this video, I will discuss the consequences of benzodiazepine use in pregnancy, breastfeeding, and adolescents.
Consequences of Benzodiazepine Use in Pregnancy, Breastfeeding, and Adolescence Slide 1 of 21

Slide 2 of 21

In pregnancy, the American College of Obstetrics and Gynecology, ACOG's guidelines, recommends that benzodiazepines be avoided or prescribed sparingly as treatment for perinatal anxiety.
References:
  • ACOG Publications (2023). American College of Obstetricians and Gynecologists, 141(5), 1036.
Consequences of Benzodiazepine Use in Pregnancy, Breastfeeding, and Adolescence Slide 2 of 21
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Slide 3 of 21

Under FDA's old pregnancy risk classification system, benzodiazepines were a Category D drug due to concerns for development of cleft lip and palate as well as urogenital and neurological malformations. However, recent studies have not shown that there's an increased risk of these complications.
References:
  • ACOG Publications (2023). American College of Obstetricians and Gynecologists, 141(5), 1036.
  • Gold, J., & Ward, K. (2022). AAPP Pharmacist Toolkit: Benzodiazepine Taper. American Association of Psychiatric Pharmacists. Updated January 9, 2023. Available from https://aapp.org/guideline/benzo.
  • Benzodiazepine Information Coalition. (2023, December 9). FDA updates risks of benzodiazepine use during pregnancy. https://www.benzoinfo.com/2022/08/04/fda-updates-risks/
Consequences of Benzodiazepine Use in Pregnancy, Breastfeeding, and Adolescence Slide 3 of 21

Slide 4 of 21

The recommendation remains that patients should try to taper off benzodiazepines in pregnancy and if tolerated, a more rapid taper over a period of a month or so may be employed.
References:
  • ACOG Publications (2023). American College of Obstetricians and Gynecologists, 141(5), 1036.
  • Gold, J., & Ward, K. (2022). AAPP Pharmacist Toolkit: Benzodiazepine Taper. American Association of Psychiatric Pharmacists. Updated January 9, 2023. Available from https://aapp.org/guideline/benzo.
  • Benzodiazepine Information Coalition. (2023, December 9). FDA updates risks of benzodiazepine use during pregnancy. https://www.benzoinfo.com/2022/08/04/fda-updates-risks/
Consequences of Benzodiazepine Use in Pregnancy, Breastfeeding, and Adolescence Slide 4 of 21
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Slide 5 of 21

There's some low-strength evidence that there could be an increased risk of ectopic pregnancy and spontaneous abortion in patients that are on these medications during the first trimester. If possible, benzodiazepine use should be avoided during the first trimester.
References:
  • ACOG Publications (2023). American College of Obstetricians and Gynecologists, 141(5), 1036.
  • Benzodiazepine Information Coalition. (2023, December 9). FDA updates risks of benzodiazepine use during pregnancy. https://www.benzoinfo.com/2022/08/04/fda-updates-risks/
Consequences of Benzodiazepine Use in Pregnancy, Breastfeeding, and Adolescence Slide 5 of 21

Slide 6 of 21

If a patient is already on a benzodiazepine when they become pregnant, it's important to discuss and weigh with them the benefits versus the risks of continuing to use these medications.
References:
  • ACOG Publications (2023). American College of Obstetricians and Gynecologists, 141(5), 1036.
  • Benzodiazepine Information Coalition. (2023, December 9). FDA updates risks of benzodiazepine use during pregnancy. https://www.benzoinfo.com/2022/08/04/fda-updates-risks/
  • Gold, J., & Ward, K. (2022). AAPP Pharmacist Toolkit: Benzodiazepine Taper. American Association of Psychiatric Pharmacists. Updated January 9, 2023. Available from https://aapp.org/guideline/benzo.
Consequences of Benzodiazepine Use in Pregnancy, Breastfeeding, and Adolescence Slide 6 of 21
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Slide 7 of 21

If a patient is already pregnant and a benzodiazepine is needed, consider an agent with a shorter half-life while still using the medication sparingly and intermittently.
References:
  • ACOG Publications (2023). American College of Obstetricians and Gynecologists, 141(5), 1036.
  • Gold, J., & Ward, K. (2022). AAPP Pharmacist Toolkit: Benzodiazepine Taper. American Association of Psychiatric Pharmacists. Updated January 9, 2023. Available from https://aapp.org/guideline/benzo.
  • Benzodiazepine Information Coalition. (2023, December 9). FDA updates risks of benzodiazepine use during pregnancy. https://www.benzoinfo.com/2022/08/04/fda-updates-risks/
Consequences of Benzodiazepine Use in Pregnancy, Breastfeeding, and Adolescence Slide 7 of 21

Slide 8 of 21

If a benzodiazepine is needed and there's no contraindication, consider switching to an antidepressant to help address ongoing anxiety as these may be safer in pregnancy. Of note, the one antidepressant that is known to be unsafe in pregnancy is paroxetine, so this should be avoided.
References:
  • ACOG Publications (2023). American College of Obstetricians and Gynecologists, 141(5), 1036.
  • Gold, J., & Ward, K. (2022). AAPP Pharmacist Toolkit: Benzodiazepine Taper. American Association of Psychiatric Pharmacists. Updated January 9, 2023. Available from https://aapp.org/guideline/benzo.
  • Benzodiazepine Information Coalition. (2023, December 9). FDA updates risks of benzodiazepine use during pregnancy. https://www.benzoinfo.com/2022/08/04/fda-updates-risks/
Consequences of Benzodiazepine Use in Pregnancy, Breastfeeding, and Adolescence Slide 8 of 21
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Slide 9 of 21

It is recommended that use is avoided or benzodiazepines are tapered off during the third trimester due to risk of neonatal sedation, decreased muscle tone, respiratory depression, increased risk of NICU admission and benzodiazepine withdrawal symptoms in the newborn.
References:
  • ACOG Publications (2023). American College of Obstetricians and Gynecologists, 141(5), 1036.
  • Gold, J., & Ward, K. (2022). AAPP Pharmacist Toolkit: Benzodiazepine Taper. American Association of Psychiatric Pharmacists. Updated January 9, 2023. Available from https://aapp.org/guideline/benzo.
  • Benzodiazepine Information Coalition. (2023, December 9). FDA updates risks of benzodiazepine use during pregnancy. https://www.benzoinfo.com/2022/08/04/fda-updates-risks/
Consequences of Benzodiazepine Use in Pregnancy, Breastfeeding, and Adolescence Slide 9 of 21

Slide 10 of 21

With regard to breastfeeding and benzodiazepine use, it's important that we are aware that benzodiazepines can cross into breast milk.
References:
  • Gold, J., & Ward, K. (2018). Pharmacist Toolkit: Benzodiazepine Taper. CPNP. https://www.opioidlibrary.org/wp-content/uploads/2019/07/CPNP_BenzoTapering.pdf
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Slide 11 of 21

The long-term effects of benzodiazepines on infants that are breastfed is unknown. We do know that babies can experience side effects from exposure to benzodiazepines including sedation, respiratory depression, difficulty breastfeeding and hypotonia or low muscle tone sometimes referred to as floppy baby syndrome.
References:
  • Gold, J., & Ward, K. (2018). Pharmacist Toolkit: Benzodiazepine Taper. CPNP. https://www.opioidlibrary.org/wp-content/uploads/2019/07/CPNP_BenzoTapering.pdf
Consequences of Benzodiazepine Use in Pregnancy, Breastfeeding, and Adolescence Slide 11 of 21

Slide 12 of 21

Again, similar to the recommendations with pregnancy, if it's necessary that a patient is on these medications during breastfeeding, use an agent with a shorter half-life.
References:
  • Gold, J., & Ward, K. (2018). Pharmacist Toolkit: Benzodiazepine Taper. CPNP. https://www.opioidlibrary.org/wp-content/uploads/2019/07/CPNP_BenzoTapering.pdf
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Slide 13 of 21

In adolescents, it is also recommended that the use of benzodiazepines is largely avoided and, if necessary, used sparingly.
References:
  • Johnston, L. D., Miech, R. A., O’Malley, P. M., Bachman, J. G., Schulenberg, J. E., & Patrick, M. E. (2019). Monitoring the Future National Survey Results on Drug Use 1975-2018: Overview, Key Findings on Adolescent Drug Use. University of Michigan, Institute for Social Research. Accessed October 20, 2020. 13
Consequences of Benzodiazepine Use in Pregnancy, Breastfeeding, and Adolescence Slide 13 of 21

Slide 14 of 21

Adolescence is a time of rapid brain growth and remodeling especially in the frontal lobe. As a result of this rapid brain growth, we know that adolescents are developing increased cognitive control and decision-making capacities while also starting to have a decrease in their impulsivity and risk-taking.
References:
  • Silveri, M. M., Sneider, J. T., Crowley, D. J., Covell, M. J., Acharya, D., Rosso, I. M., & Jensen, J. E. (2013). Frontal lobe γ-aminobutyric acid levels during adolescence: Associations with impulsivity and response inhibition. Biological Psychiatry, 74(4), 296-304. 
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Slide 15 of 21

Our goal is to work with adolescents to increase their coping skills and distress tolerance through practice and support and not to have them become reliant on turning to a medication to address distress and anxiety and insomnia.
References:
  • Silveri, M. M., Sneider, J. T., Crowley, D. J., Covell, M. J., Acharya, D., Rosso, I. M., & Jensen, J. E. (2013). Frontal lobe γ-aminobutyric acid levels during adolescence: Associations with impulsivity and response inhibition. Biological Psychiatry, 74(4), 296-304. 
Consequences of Benzodiazepine Use in Pregnancy, Breastfeeding, and Adolescence Slide 15 of 21

Slide 16 of 21

Due to the impulsivity and risk-taking of adolescents, they are more likely to misuse benzodiazepines than the general adult population.
References:
  • Johnston, L. D., Miech, R. A., O’Malley, P. M., Bachman, J. G., Schulenberg, J. E., & Patrick, M. E. (2019). Monitoring the future National survey results on drug use 1975-2018: Overview, key findings on adolescent drug use. University of Michigan, Institute for Social Research. Accessed October 20, 2020.
  • Silveri, M. M., Sneider, J. T., Crowley, D. J., Covell, M. J., Acharya, D., Rosso, I. M., & Jensen, J. E. (2013). Frontal lobe γ-aminobutyric acid levels during adolescence: Associations with impulsivity and response inhibition. Biological Psychiatry, 74(4), 296-304. 
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Slide 17 of 21

Overall, adolescents are at increased risk for developing substance use disorders due to their developing brains. And when exposed to substances in adolescence, this may further increase their risk of developing a use disorder in adulthood.
References:
  • Johnston, L. D., Miech, R. A., O’Malley, P. M., Bachman, J. G., Schulenberg, J. E., & Patrick, M. E. (2019). Monitoring the Future National Survey Results on Drug Use 1975-2018: Overview, Key Findings on Adolescent Drug Use. University of Michigan, Institute for Social Research. Accessed October 20, 2020.
  • Silveri, M. M., Sneider, J. T., Crowley, D. J., Covell, M. J., Acharya, D., Rosso, I. M., & Jensen, J. E. (2013). Frontal lobe γ-aminobutyric acid levels during adolescence: Associations with impulsivity and response inhibition. Biological Psychiatry, 74(4), 296-304. 
Consequences of Benzodiazepine Use in Pregnancy, Breastfeeding, and Adolescence Slide 17 of 21

Slide 18 of 21

To review the key points for this video, when possible, avoid use of benzodiazepines in pregnancy, encourage pregnant patients to work on tapering off by third trimester to limit the risk of adverse effects on the infant.
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Slide 19 of 21

Be aware that benzodiazepines do pass into the breast milk and pose a risk to the infant due to their difficulty metabolizing them. Overall, in pregnancy, recommended that the shorter half-life benzodiazepines are used sparingly if required.
Consequences of Benzodiazepine Use in Pregnancy, Breastfeeding, and Adolescence Slide 19 of 21

Slide 20 of 21

And finally, recommended that benzodiazepines use is largely avoided and, if necessary, used in a limited fashion in adolescents due to the increased risk of misuse in this population.
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Slide 21 of 21

Consequences of Benzodiazepine Use in Pregnancy, Breastfeeding, and Adolescence Slide 21 of 21

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10. Clinical Vignette: Strategies for Safer Use of Benzodiazepines

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CME Information

Learning Objectives:

After completing this activity, the learner will be able to:

  1. Identify the risks and contraindications associated with benzodiazepines.
  2. Understand the clinical consequences of benzodiazepine misuse and addiction.
  3. Apply effective strategies for safer benzodiazepine prescribing.

Original Release Date: May 1, 2024

Expiration Date: May 1, 2027

Expert: Alexis Ritvo, M.D.

Medical Editor: Paz Badía, M.D. 

Relevant Financial Disclosures: 

None of the faculty, planners, and reviewers for this educational activity have relevant financial relationships to disclose during the last 24 months with ineligible companies whose primary business is producing, marketing, selling, re-selling, or distributing healthcare products used by or on patients.

Contact Information: For questions regarding the content or access to this activity, contact us at support@psychopharmacologyinstitute.com

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Participants must complete the activity online during the valid credit period that is noted above.

Follow these steps to earn CME credit:

  1. View the required educational content provided on this course page.

  2. Complete the Post Activity Evaluation for providing the necessary feedback for continuing accreditation purposes and for the development of future activities. NOTE: Completing the Post Activity Evaluation after the quiz is required to receive the earned credit.

  3. Download your certificate.

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This activity has been planned and implemented in accordance with the accreditation requirements and policies of the Accreditation Council for Continuing Medical Education through the joint providership of Medical Academy LLC and the Psychopharmacology Institute. Medical Academy is accredited by the ACCME to provide continuing medical education for physicians.

Credit Designation Statement

Medical Academy designates this enduring activity for a maximum of 1.0 AMA PRA Category 1 credit(s)™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

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