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Are antidepressants during pregnancy safe? The answer is in your DNA

There are risks and benefits with taking any medication. Women are understandably concerned about the safety of antidepressants and wonder if they should continue taking them during pregnancy. Worries over drugs’ impact on the fetus may lead to discontinuation of anxiety or depression medication. Although some antidepressants can affect developing fetuses, women should consider their overall health and family wellness in making this decision. While many antidepressants can be taken safely during and after pregnancy, there can be changes in their effectiveness and their risk of side effects during this time. Here we describe how your DNA plays an essential role in the efficacy of antidepressants during pregnancy and impacts these medications’ safety.

Depression during and after pregnancy is not uncommon

Up to 20% of pregnant women experience mood changes. Approximately 2–3% of pregnant women take antidepressants during pregnancy, including treatment of pre-existing depression, and even more mothers need treatment after birth for post-partum depression.

Most antidepressants during pregnancy are safe

A recent national health records study of 30,630 mothers examined which antidepressants used during pregnancy are associated with specific congenital disabilities. This case-control study of infants with birth defects and over 11,000 healthy babies identified a link between specific antidepressants and birth defects. Selective serotonin reuptake inhibitors (SSRIs) are the most commonly used antidepressants, but only venlafaxine (Effexor) and bupropion (Wellbutrin) were linked to an elevated risk of birth defects such as heart abnormalities. This study supports that taking an antidepressant during pregnancy carries a small or non-existent risk of fetal/congenital malformations. At the same time, untreated maternal depression has its own risks for both mothers and newborns due to lower quality of life and maternal care. With careful medication selection and dosage, most women can take antidepressants with minimal risk to themselves and their babies.

Altered drug metabolism of antidepressants during pregnancy

We all know that a great deal of change happens to a woman’s body during pregnancy. This includes changes in the metabolism of medications that can impact the effectiveness of antidepressants. The metabolism of many antidepressants is dependent on liver enzymes, specifically two enzymes called CYP2D6 and CYP2C19. These are responsible for the clearance of medications from the body. Their activity is altered by pregnancy in different ways. Therefore, some antidepressants can become less effective, while others may cause negative side effects due to increased drug concentration in the bloodstream.

chart of liver enzyme activity changes during pregnancy
The CYP2D6 liver enzyme is “induced” during pregnancy – i.e. for some women, this enzyme becomes more active during pregnancy. Fluoxetine (Prozac) and other antidepressants metabolized by CYP2D6 have demonstrated decreased drug concentration during pregnancy. Low fluoxetine concentrations increase the risk of relapse of depressive symptoms. In addition to fluoxetine, paroxetine (Paxil), fluvoxamine (Luvox), vortioxetine (Trintellix) and venlafaxine (Effexor) are all affected by the CYP2D6 enzyme, and hence can be less effective for pregnant women.

Your DNA determines the effectiveness and toxicity of antidepressants during pregnancy

The decrease in drug’s efficacy is also strongly linked to woman’s inherited drug metabolism. Specific genetic variations determine the baseline activity of liver enzymes. Some individuals may have inherently higher than average activity. These are classified as “Ultrarapid Metabolizers.” For these women, many antidepressants are less effective due to faster drug clearance. During pregnancy, CYP2D6-dependent drugs will become even less effective than before.

The CYP2D6 Enzyme

Women that have an absent activity of this enzyme are known as CYP2D6 “Poor Metabolizers.” They are at higher risk of side effects and need much lower doses of fluoxetine, paroxetine, fluvoxamine, vortioxetine and many other drugs. However, with pregnancy, there is no change or improvement in enzymatic activity. The reported congenital toxicity of venlafaxine might be limited to women with reduced CYP2D6 enzyme activity and significant drug-induced toxicity, harmful both for the mother and the fetus.

Women with an intermediate activity of the CYP2D6 liver enzyme may experience improved tolerability of antidepressants during pregnancy, but most likely, no dose increase will be necessary. For women with normal CYP2D6 activity, a dose increase might be warranted to assure antidepressant’s effectiveness during pregnancy.

As the chart below shows, almost half of North Americans have altered CYP2D6 metabolism.

graph of distribution of CYP2D6 activity

The CYP2C19 Enzyme

The effectiveness of citalopram (Celexa), escitalopram (Cipralex, Lexapro) and sertraline (Zoloft) during pregnancy changes in the opposite way than the antidepressants described above. These three antidepressants are cleared from the body by the CYP2C19 liver enzyme. During pregnancy, there is decreased CYP2C19 metabolism of these drugs. Therefore, for most women, the tolerability of citalopram, escitalopram and sertraline may go down. For women with absent or significantly reduced activity of this enzyme, citalopram and sertraline pose a higher risk of toxicity for both the mother and developing fetus.

Up to 18% of women have increased activity of the CYP2C19 enzyme, i.e. they are rapid metabolizers, and during pregnancy, they may respond well to these medications. However, after delivery, citalopram and escitalopram can become ineffective. Some anti-anxiety drugs called benzodiazepines are also metabolized by the CYP2C19 and might be more toxic during pregnancy.

More than half of North Americans have altered CYP2C19 metabolism (see chart below).

graph of distribution of CYP2C19 activity

A pharmacogenetic test can help to select the optimal treatment for depression, anxiety and ADHD

In addition to antidepressants, pregnancy can significantly affect medication response for women with epilepsy and ADHD, depending on a person’s DNA profile. Pharmacogenetic testing, such as Pillcheck, provides insights into how your body processes medications. In addition to antidepressants, anxiety and ADHD drugs, Pillcheck also covers pain, antiepileptic, and cardiovascular drugs. The effectiveness of these medications may also change during pregnancy.

Pillcheck can help you avoid potential drug toxicity by flagging which medications are cleared slower by your liver enzymes to improve treatment safety. The service also includes a personalized medication action plan by a clinical pharmacist, specially trained in pharmacogenetics. By determining your metabolizer type, Pillcheck can support you and your doctor in deciding how to manage your medications during pregnancy and after delivery.

Summary

  • Pregnancy can significantly change your metabolism of medications.
  • Some medications can become less effective while others more toxic, depending on your DNA.
  • Pharmacogenetic testing can reveal how your body clears different medications and reduce the risk of toxicity for you and the unborn.
  • A qualified pharmacist can review the medications you are currently taking and advise your doctor on adjusting treatment to ensure antidepressant’s safety and effectiveness during pregnancy and after delivery.

Use Pillcheck to get on the right medications and feel better sooner.

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Pillcheck is an eligible medical expense for income tax deduction and may be reimbursed through your private insurance or company benefits plan.

References

Anderson KN et al. Maternal Use of Specific Antidepressant Medications During Early Pregnancy and the Risk of Selected Birth Defects JAMA Psychiatry. Published online August 5, 2020. doi:10.1001/jamapsychiatry.2020.2453

Cesta CE et al. Incidence of Malformations After Early Pregnancy Exposure to Modafinil in Sweden and Norway JAMA. 2020;324(9):895-897. doi:10.1001/jama.2020.9840

Dean L Venlafaxine Therapy and CYP2D6 Genotype National Center for Biotechnology Information (US), Bethesda (MD), June 28 2020 PMID: 28520361

Dubovicky M et al., Risks of using SSRI / SNRI antidepressants during pregnancy and lactation Interdiscip Toxicol. 2017 Sep; 10(1): 30–34. Published online 2018 February 14. doi: 10.1515/intox-2017-0004

Deligiannidis KM et al., Pharmacotherapy for mood disorders in pregnancy: a review of pharmacokinetic changes and clinical recommendations for therapeutic drug monitoring. J Clin Psychopharmacol. 2014 Apr;34(2):244-55.

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