Sertraline, Folic Acid, and Hepatic Health During Pregnancy

The Impact of Sertraline on Liver Function in Pregnant Women

Sertraline is primarily metabolized by the liver through cytochrome P450 (CYP) enzymes, particularly CYP2C19, CYP2B6, and CYP3A4. Chronic administration of sertraline has been linked to elevated liver enzymes, indicating potential liver damage or dysfunction (Medicina, 2025). Studies have shown that pregnant women using sertraline may experience alterations in liver function tests, including increased alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, which are indicative of hepatocellular injury (Medicina, 2025).

The liver plays a pivotal role in drug metabolism, and pregnancy can alter the pharmacokinetics of medications due to changes in liver enzyme activity and blood flow. This can lead to increased sensitivity to hepatotoxic effects, particularly when using medications such as sertraline. The potential for hepatotoxicity is compounded by the physiological changes that occur during pregnancy, such as increased estrogen levels, which can further influence liver function and enzyme activity (Medicina, 2025).

Biochemical and Histological Changes Induced by Sertraline

The biochemical changes induced by sertraline treatment during pregnancy can lead to significant alterations in liver function. Increased levels of ALT and AST are often observed in pregnant women taking sertraline, signifying liver stress and potential injury. Histologically, liver tissues from sertraline-treated rats exhibit signs of hepatocellular vacuolation, necrosis, and inflammation, indicating the severity of liver damage (Medicina, 2025).

Table 1: Biochemical Markers of Liver Function

As shown in Table 1, sertraline administration leads to a notable increase in liver enzymes and lipid profile disturbances compared to control groups. Conversely, folic acid supplementation appears to mitigate these changes, thereby supporting the liver’s structural integrity and function.

Protective Role of Folic Acid Against Sertraline-Induced Damage

Folic acid, a B-vitamin known for its crucial role in DNA synthesis and cell division, has been widely recommended for pregnant women. Its potential hepatoprotective effects have garnered attention, particularly concerning its ability to counteract the adverse effects of medications such as sertraline. Research has demonstrated that folic acid supplementation can normalize liver enzyme levels, improve lipid profiles, and reduce histological damage in hepatic tissues exposed to sertraline (Medicina, 2025).

Folic acid’s antioxidant properties help reduce oxidative stress and inflammation, which are critical in mitigating liver injury. It plays a significant role in maintaining cellular integrity and promoting regeneration, particularly in the context of drug-induced liver damage. The combination of sertraline and folic acid results in significantly lower levels of caspase 3 expression, indicating reduced apoptosis and enhanced liver cell survival (Medicina, 2025).

Table 2: Histopathological Scoring of Liver Tissue

As demonstrated in Table 2, the histopathological assessment reveals a significant reduction in sinusoidal congestion, vacuolation, and necrosis in the folic acid + sertraline group compared to those treated with sertraline alone, further corroborating the protective role of folic acid (Medicina, 2025).

Mechanisms of Liver Injury and Apoptosis Related to Sertraline

The mechanisms by which sertraline induces liver injury are multifactorial. It is hypothesized that sertraline induces oxidative stress, leading to mitochondrial dysfunction and subsequent hepatocyte apoptosis. Increased production of reactive oxygen species (ROS) and the activation of apoptotic pathways, particularly those mediated by caspase enzymes, are critical in this process (Medicina, 2025).

Sertraline’s impact on liver function may also be attributed to its interference with lipid metabolism. Studies indicate that sertraline may alter hepatic lipid metabolism, leading to fatty liver changes characterized by hepatocellular vacuolation. This alteration can be exacerbated by pregnancy-related hormonal changes that influence drug metabolism and hepatic enzyme activity (Medicina, 2025).

Recommendations for Safe Sertraline Use During Pregnancy

Given the potential hepatotoxic effects of sertraline during pregnancy, it is crucial to consider the following recommendations:

1. Monitoring Liver Function: Regular assessment of liver enzyme levels (ALT and AST) should be conducted for pregnant women receiving sertraline to promptly identify any hepatic dysfunction.

2. Folic Acid Supplementation: Folic acid should be routinely supplemented during pregnancy, especially in women prescribed sertraline, to mitigate the risk of liver injury and support overall maternal health.

3. Individualized Treatment Plans: Clinicians should evaluate the risks and benefits of continuing sertraline during pregnancy, considering alternative therapies or non-pharmacological interventions for mood disorders when appropriate.

4. Multidisciplinary Approach: Collaboration between obstetricians, psychiatrists, and nutritionists can optimize treatment strategies for pregnant women requiring antidepressant therapy, ensuring both maternal and fetal well-being.

5. Further Research: Additional studies are warranted to explore the long-term effects of sertraline on liver function during pregnancy and the potential benefits of folic acid supplementation.

FAQ

What is sertraline and why is it prescribed during pregnancy?
Sertraline is a selective serotonin reuptake inhibitor (SSRI) commonly prescribed to treat anxiety and depression. It is often used during pregnancy to support maternal mental health.

What are the potential side effects of sertraline on liver function?
Sertraline may increase liver enzymes, indicating potential liver dysfunction, and can lead to histological changes in liver tissue, including inflammation and apoptosis.

How does folic acid help during pregnancy?
Folic acid is essential for DNA synthesis and cell division, and it has protective effects against oxidative stress and inflammation, potentially mitigating liver damage from medications like sertraline.

What should pregnant women taking sertraline do?
Pregnant women on sertraline should have regular liver function tests, consider folic acid supplementation, and work closely with healthcare providers to manage their mental health.

Are there alternatives to sertraline for managing mood disorders during pregnancy?
Yes, non-pharmacological interventions such as therapy, lifestyle changes, and mindfulness practices may be considered as alternatives to medication for managing mood disorders during pregnancy.

References

1. Medicina. (2025). Folic Acid Mitigates Sertraline-Induced Liver Damage in Adult Female Albino Rats During Pregnancy and Postpartum: A Biochemical and Histological Study. https://doi.org/10.3390/medicina61040751
2. Medicina. (2025). Sertraline, Folic Acid, and Hepatic Health During Pregnancy. https://doi.org/10.3390/jcm14082716
3. Tarawneh, N., & Abdalla, S. (2025). Repurposing Antiepileptic Drugs for Cancer: A Promising Therapeutic Strategy. https://doi.org/10.3390/jcm14082673
4. Gao, X., et al. (2025). Chemical Pollutant Exposure in Neurodevelopmental Disorders: Integrating Toxicogenomic and Transcriptomic Evidence to Elucidate Shared Biological Mechanisms and Developmental Signatures. https://doi.org/10.3390/toxics13040282