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02. Pregnancy’s Impact on Medication Efficacy and Dosing Considerations

Published on January 1, 2025 Certification expiration date: January 1, 2028

Amanda Koire, M.D.

Attending Psychiatrist - Brigham and Women's Hospital

Key Points

Pregnancy can affect medication efficacy through changes in absorption, distribution, metabolism, and elimination, potentially requiring higher doses.
For SSRIs and lamotrigine, levels may decrease during pregnancy; if symptoms re-emerge, consider increasing the dose.
Increased GFR during pregnancy can reduce lithium levels; monitor serum levels frequently and adjust dosing accordingly.

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Slides and Transcript

Slide 1 of 10

Now, let’s talk about pregnancy and medication efficacy. To start off with, pregnancy does affect medication efficacy.

Pregnancy’s Impact on Medication Efficacy and Dosing Considerations Slide 1 of 10

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It can affect how medications work in a number of ways. It can affect drug absorption. Thus, it’s associated with slower gastric emptying and slower bowel and colonic transit. It can affect drug distribution through an increase in plasma volume, changes in protein binding, and a lower ratio of lean muscle to adipose tissue.

References:

Deligiannidis, K. M., Byatt, N., & Freeman, M. P. (2014). Pharmacotherapy for mood disorders in pregnancy: A review of pharmacokinetic changes and clinical recommendations for therapeutic drug monitoring. Journal of Clinical Psychopharmacology, 34(2), 244-255. https://doi.org/10.1097/JCP.0000000000000087
Pariente, G., Leibson, T., Carls, A., Adams-Webber, T., Ito, S., & Koren, G. (2016). Pregnancy-associated changes in pharmacokinetics: A systematic review. PLoS Medicine, 13(11), e1002160. https://doi.org/10.1371/journal.pmed.1002160

Pregnancy’s Impact on Medication Efficacy and Dosing Considerations Slide 2 of 10

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Slide 3 of 10

It can also affect hepatic metabolism through an increased activity of CYP enzymes. And pregnancy can affect drug elimination notably leading to an increased renal blood flow and increased GFR, glomerular filtration rate.

References:

Deligiannidis, K. M., Byatt, N., & Freeman, M. P. (2014). Pharmacotherapy for mood disorders in pregnancy: A review of pharmacokinetic changes and clinical recommendations for therapeutic drug monitoring. Journal of Clinical Psychopharmacology, 34(2), 244-255. https://doi.org/10.1097/JCP.0000000000000087
Pariente, G., Leibson, T., Carls, A., Adams-Webber, T., Ito, S., & Koren, G. (2016). Pregnancy-associated changes in pharmacokinetics: A systematic review. PLoS Medicine, 13(11), e1002160. https://doi.org/10.1371/journal.pmed.1002160

Pregnancy’s Impact on Medication Efficacy and Dosing Considerations Slide 3 of 10

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As a result of these changes, it’s not uncommon to need higher doses of medication to maintain the same effect as pregnancy progresses. Typically, when symptoms do re-emerge, it’s often around the start of the third trimester. This doesn’t mean that you need to change dosing proactively or even always get a level. That depends on the medication. But don’t be surprised if a higher dose is needed for a while based on what is happening at the physiologic and biochemical level.

References:

Deligiannidis, K. M., Byatt, N., & Freeman, M. P. (2014). Pharmacotherapy for mood disorders in pregnancy: A review of pharmacokinetic changes and clinical recommendations for therapeutic drug monitoring. Journal of Clinical Psychopharmacology, 34(2), 244-255. https://doi.org/10.1097/JCP.0000000000000087
Abduljalil, K., & Badhan, R. K. S. (2020). Drug dosing during pregnancy—opportunities for physiologically based pharmacokinetic models. Journal of Pharmacokinetics and Pharmacodynamics, 47(4), 319-340. https://doi.org/10.1007/s10928-020-09698-w

Pregnancy’s Impact on Medication Efficacy and Dosing Considerations Slide 4 of 10

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Slide 5 of 10

There are some specific medications to know about that are affected by pregnancy in particular ways. SSRIs or selective serotonin reuptake inhibitors can be affected by hepatic CYP enzyme metabolism. Antidepressant levels may decrease especially in late pregnancy. If that happens, increase the dose if symptoms re-emerge clinically. For lamotrigine, increases in estrogen and estradiol during pregnancy can increase phase 2 glucuronidation which decreases the levels of the lamotrigine. Levels may decrease by 50% by the second trimester and patients may need an increased dose if symptoms re-emerge.

References:

Deligiannidis, K. M., Byatt, N., & Freeman, M. P. (2014). Pharmacotherapy for mood disorders in pregnancy: A review of pharmacokinetic changes and clinical recommendations for therapeutic drug monitoring. Journal of Clinical Psychopharmacology, 34(2), 244-255. https://doi.org/10.1097/JCP.0000000000000087
Abduljalil, K., & Badhan, R. K. S. (2020). Drug dosing during pregnancy—opportunities for physiologically based pharmacokinetic models. Journal of Pharmacokinetics and Pharmacodynamics, 47(4), 319-340. https://doi.org/10.1007/s10928-020-09698-w

Pregnancy’s Impact on Medication Efficacy and Dosing Considerations Slide 5 of 10

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Lithium is a medication to be aware of in pregnancy. It’s important to consider the effects of pregnancy on the dosing of lithium because the increase in GFR during pregnancy can reduce the levels of lithium and this can have important clinical effects. It can be very beneficial for lithium in particular to monitor levels quite frequently especially during the third trimester to stay in the therapeutic range.

References:

Deligiannidis, K. M., Byatt, N., & Freeman, M. P. (2014). Pharmacotherapy for mood disorders in pregnancy: A review of pharmacokinetic changes and clinical recommendations for therapeutic drug monitoring. Journal of Clinical Psychopharmacology, 34(2), 244-255. https://doi.org/10.1097/JCP.0000000000000087

Pregnancy’s Impact on Medication Efficacy and Dosing Considerations Slide 6 of 10

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Slide 7 of 10

It’s common clinical practice to hold the dose of lithium during labor and delivery then recheck the lithium level after delivery and restart the medication because at delivery vascular volume and lithium clearance changes rapidly revert to pre-pregnancy levels and you want to make sure that the postpartum individual does not experience lithium toxicity.

References:

Deligiannidis, K. M., Byatt, N., & Freeman, M. P. (2014). Pharmacotherapy for mood disorders in pregnancy: A review of pharmacokinetic changes and clinical recommendations for therapeutic drug monitoring. Journal of Clinical Psychopharmacology, 34(2), 244-255. https://doi.org/10.1097/JCP.0000000000000087

Pregnancy’s Impact on Medication Efficacy and Dosing Considerations Slide 7 of 10

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As we think about medications during pregnancy, it’s important to recognize that mood recurrence, mood episode recurrence is common with or without medications. However, mood episode recurrence is much higher if medications are discontinued. For women with a history of major depressive disorder who entered pregnancy euthymic, 68% of those who discontinued their antidepressant experienced a relapse during pregnancy compared to only 26% of those who continued their medication.

References:

Deligiannidis, K. M., Byatt, N., & Freeman, M. P. (2014). Pharmacotherapy for mood disorders in pregnancy: A review of pharmacokinetic changes and clinical recommendations for therapeutic drug monitoring. Journal of Clinical Psychopharmacology, 34(2), 244-255. https://doi.org/10.1097/JCP.0000000000000087
Cohen, L. S., Altshuler, L. L., Harlow, B. L., Nonacs, R., Newport, D. J., Viguera, A. C., Suri, R., Burt, V. K., Hendrick, V., Reminick, A. M., Loughead, A., Vitonis, A. F., & Stowe, Z. N. (2006). Relapse of major depression during pregnancy in women who maintain or discontinue antidepressant treatment. JAMA, 295(5), 499-507. https://doi.org/10.1001/jama.295.5.499

Pregnancy’s Impact on Medication Efficacy and Dosing Considerations Slide 8 of 10

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For women with a history of bipolar disorder who entered pregnancy euthymic, 85.5% of those who discontinued their mood stabilizer experienced a relapse during pregnancy, which may have been a depressive episode, manic, hypomanic, or mixed episode compared to 27% of those who continued treatment. So in both cases, the risk of relapse is far higher when discontinuing medications but it is not trivial even when maintaining treatment.

References:

Deligiannidis, K. M., Byatt, N., & Freeman, M. P. (2014). Pharmacotherapy for mood disorders in pregnancy: A review of pharmacokinetic changes and clinical recommendations for therapeutic drug monitoring. Journal of Clinical Psychopharmacology, 34(2), 244-255. https://doi.org/10.1097/JCP.0000000000000087
Cohen, L. S., Altshuler, L. L., Harlow, B. L., Nonacs, R., Newport, D. J., Viguera, A. C., Suri, R., Burt, V. K., Hendrick, V., Reminick, A. M., Loughead, A., Vitonis, A. F., & Stowe, Z. N. (2006). Relapse of major depression during pregnancy in women who maintain or discontinue antidepressant treatment. JAMA, 295(5), 499-507. https://doi.org/10.1001/jama.295.5.499

Pregnancy’s Impact on Medication Efficacy and Dosing Considerations Slide 9 of 10

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To wrap up, here are some key points for this section. The physiology of pregnancy may lead to a need for increase of a previously stable medication dose. Dosing should generally be guided by clinical presentation rather than theory. Recurrence of a mood disorder may occur even when a patient continues medication treatment during pregnancy but is far more likely if they have discontinued their medications.

Pregnancy’s Impact on Medication Efficacy and Dosing Considerations Slide 10 of 10

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Next Section

03. Psychiatric Medications in Pregnancy: Balancing Maternal and Fetal Well-Being

Learning Objectives:

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

Describe the prevalence and barriers to treatment of perinatal mental health conditions.
Explain how pregnancy affects medication efficacy through physiological changes and recognize when dose adjustments may be needed for common psychiatric medications
Evaluate and discuss the risks and benefits of continuing versus discontinuing psychiatric medications during pregnancy, incorporating evidence-based data to inform shared decision-making with patients

Original Release Date: January 1, 2025

Expiration Date: January 1, 2028

Expert: Amanda Koire, M.D.

Medical Editor: Flavio Guzmán, 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.

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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 0.5 AMA PRA Category 1 credit(s)™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.