Antipsychotic Medication During Pregnancy Lowers Schizophrenia Relapse Risk

Understanding the complexities of psychotropic medication use during pregnancy is crucial for both healthcare providers and expecting mothers. The nuances involved in this topic require careful consideration, as the implications can significantly affect both maternal and fetal health.

Numerous Mental Elf blogs have delved into this significant topic. For instance, Joanne Wallace highlighted a comprehensive cohort study demonstrating that the use of antipsychotic medications did not correlate with an increased risk of major congenital malformations. Recently, Flo Martin addressed findings from an umbrella review that underscored the scarcity of robust evidence in this area. Two key points emerge from these discussions. First, as Martin notes, the foundation of this evidence is predominantly observational, given that pregnant women are typically excluded from randomized controlled trials. Second, Wallace poignantly states, “For each individual woman, the decision to continue or discontinue psychotropic treatment encompasses a range of factors, and for some, this could be the hardest decision of their lives.”

To empower expectant mothers in weighing the risk-benefit balance of antipsychotic medication during pregnancy, it is vital to comprehend the potential risks and benefits associated with such treatments. A noteworthy study conducted by Kang et al. (2025), utilizing the National Health Information Database of South Korea, presents a detailed analysis aimed at enhancing our grasp of this essential clinical issue.

Exploring Research Methods for Antipsychotic Use in Expecting Mothers

The National Health Information Database in South Korea provides comprehensive data from the sole provider of mandatory health insurance for the entire national population. This study specifically identified women who delivered live births at least two years subsequent to their initial diagnosis of schizophrenia and were under the age of 50 (n = 3,026).

To address potential confounding variables, particularly the severity of schizophrenia, the researchers employed the self-controlled case series method. In this straightforward yet sophisticated approach, each participant serves as her own control. The study calculated the incidence rate ratio (IRR) by comparing the rate of psychosis admissions within six months postpartum against the rate during a reference period that spanned two years before delivery to one year before delivery.

The participants were classified into three distinct groups:

• Non-users: Women who abstained from antipsychotic medication from one year prior to delivery up to 39 weeks before delivery,
• Discontinuers: Women who used antipsychotics within one year to 39 weeks before delivery but ceased usage before delivery, or,
• Continuers: Women who maintained their antipsychotic treatment from one year to 39 weeks before delivery and continued usage until delivery.

The authors subsequently calculated the relative risk ratios (RRRs) for the IRRs for each group, using the discontinuers as the reference group.

Key Findings on Antipsychotic Medication Use During Pregnancy

Among the 3,026 women diagnosed with schizophrenia, 43.1% were non-users, while 41.6% were discontinuers. Only 15.3% of women continued their antipsychotic medication throughout their pregnancy.

Overall, the IRR for postpartum psychosis admissions was 2.35 (95% confidence interval [CI] 1.99 to 2.78) compared to the reference period, indicating a significantly heightened risk of postpartum admission across the entire study sample. This risk peaked immediately following delivery (one to ten days postpartum, with an IRR of 5.44) and gradually decreased over time, eventually aligning with reference period rates within one to two years postpartum.

When examining various medication categories, the incident rates during the reference period revealed that continuers had the highest rates (144.7 per 1,000 person-years), compared to discontinuers (118.3 per 1,000 person-years) and non-users (29.9 per 1,000 person-years). However, significant increases in incident rates were observed during the six-month postpartum period for non-users (128.5 per 1,000 person-years) and discontinuers (277.9 per 1,000 person-years), while continuers showed a smaller increase (191.3 per 1,000 person-years). Consequently, the IRR of relapse was highest for the non-user group (4.18, 95% CI 2.85 to 6.12), followed by the discontinuer group (IRR 2.34, 95% CI 1.87 to 2.91). The IRR for the continuer group was not significant (IRR 1.31, 95% 0.89 to 1.92), highlighting that the risk of relapse did not show significant differences for the continuer group before or after delivery. Using the continuer group as a reference, the IRR was significantly elevated for the non-user group (RRR = 1.79, 95% CI 1.15 to 2.78) and significantly reduced for the continuer group (RRR = 0.56, 95% CI 0.36 to 0.87).

The authors performed seven subgroup analyses based on various factors: (i) age at delivery (younger than 34 or 34 and older), (ii) insurance premiums, (iii) delivery mode (vaginal or Caesarean), (iv) number of prenatal care visits (fewer than 13 or 13 and more), (v) diagnosis of schizoaffective disorder, (vi) comorbid depressive disorders, and (vii) comorbid mood disorders. Furthermore, six sensitivity analyses were conducted to evaluate how changes in assumptions or inputs impacted statistical results. These tests included: (i) excluding admissions with concurrent antidepressant use, (ii) adjusting the reference period to two to three years before delivery, (iii) excluding women admitted for psychosis within one year prior to delivery, (iv) focusing on women who used antipsychotics within the 13 weeks leading up to delivery, (v) modifying the grace period for discontinuation to 14 or 60 days instead of 30 days, and (vi) excluding women admitted for more than seven days during childbirth.

These subgroup and sensitivity analyses predominantly confirmed the overall trend of higher relapse risk for the non-user group and lower risk for the continuer group in comparison to the discontinuer group, although not all sub-analyses yielded clear statistical distinctions as seen in the primary analysis.

Additionally, the authors explored the timing of antipsychotic discontinuation over various timeframes (one year to 39 weeks before delivery, 39 to 26 weeks, 26 to 13 weeks, and 13 weeks to delivery). Their findings indicated that the risk of relapse was unaffected by the timing of antipsychotic discontinuation.

Insights on Antipsychotic Use and Postpartum Relapse Risks

The authors concluded:

In women diagnosed with schizophrenia, the continuation of antipsychotic treatment during pregnancy was linked to a reduced risk of experiencing postpartum relapse.

Evaluating the Strengths and Limitations of the Study

As highlighted earlier, the evidence surrounding pregnant women is primarily derived from observational studies. In this study, the authors employed several statistical techniques to mitigate potential biases and limitations. First, the research utilized a nationwide database that encompasses almost all women with schizophrenia who delivered live births in South Korea. Second, the self-controlled case series method was utilized to account for the severity of schizophrenia among women within the dataset. Third, the authors carried out multiple subgroup and sensitivity analyses to adjust for individuals with comorbid bipolar disorder and depressive disorder, as well as the use of other psychotropic medications like antidepressants and mood stabilizers.

Despite these strengths, several limitations warrant attention. The study’s findings, conducted within the context of South Korea, may not be easily generalizable to practices in Australia or other non-South Korean countries. This raises questions about the potential influence of comorbid substance use disorders or psychotogenic substance use on decision-making processes among women in South Korea compared to those in Australia. Furthermore, as the authors acknowledge, the study could not examine the specific types of antipsychotic medications used.

While it may not be feasible to explore each unique type of antipsychotic, we ponder whether differences exist between oral and depot formulations, for instance. Additionally, as is the case with most routinely collected health data, it is crucial to recognize that medication prescriptions do not always reflect actual consumption. Lastly, the outcome of interest examined—hospital admission for psychosis—may not fully capture the benefits and risks associated with the medication exposure. For example, there may have been numerous women whose psychotic symptoms worsened during the study period without requiring hospitalization for various reasons.

Practical Implications for Mental Health Professionals

The process of pregnancy can be overwhelming, filled with numerous decisions that often come with stringent timelines. Some choices may feel paralyzing, while others can have profound implications for both mother and child. During our training, we encountered numerous health professionals who insisted that pregnant women are distinct; they are shielded from mental illness by the impending experience of motherhood. Some even subtly suggested that we refrain from burdening pregnant women with unnecessary medications. We now understand that this notion is misguided; in fact, pregnancy often represents a vulnerable period for women with schizophrenia (Lefebvre et al., 2022). However, from a clinician’s perspective, it is indeed true that pregnant women often display heightened motivation to become the best parents possible. This often leads them to make sacrifices—abandoning cigarettes, alcohol, and other harmful substances, as well as sometimes discontinuing their psychotropic medications.

There tends to be an almost instinctual response among practitioners to recommend the cessation of psychotropic medications upon confirmation of pregnancy, which can have significant adverse effects on the mental health of those pregnant women. Making clinical decisions in this context is challenging, as all existing evidence is inherently based on the experiences of others’ pregnancies and their outcomes. Each pregnancy is unique, and you can only assess the effects on one child at a time. Often, we must respect the mother’s decision, monitor her condition as closely as possible, and remain hopeful for both her and her baby’s well-being. Sometimes pregnancies proceed without complications, while other times we face difficult choices. It is essential to prioritize shared decision-making and maintain close collaboration with obstetric and midwifery colleagues. Ideally, these decisions should involve the mother, although at times they may occur against her preferences.

Wherever possible, shared decision-making and close liaison with obstetric and midwifery colleagues are key.

Pregnancy necessitates a dual focus—not only on the pregnant woman presenting for care but also on her unborn child. A conscientious practitioner recognizes the importance of considering the postnatal period and the implications for breastfeeding. Clinicians often remember the cases that did not go well while overlooking those that did.

When discussing the risk-benefit ratio of antipsychotic medications with pregnant women, it is crucial to acknowledge the potential biases—such as availability bias—that may influence our decisions, as well as hindsight bias, which can distort our perceptions. To thoroughly investigate the risks and benefits of medication use during pregnancy, routinely collected clinical data, like that examined in the current study, is vital for enhancing our clinical practice. Some might argue that it is our ethical responsibility to scrutinize such data scientifically, as doing so could lead to deeper insights and improved outcomes for both mothers and their children (Grzeskowiak et al., 2013). However, when deriving meaning from such findings, we must remain aware of the limitations inherent in the interpretation process.

As discussed in the limitations section, the available data is restricted to what has been collected, which may result in a loss of intricacies associated with different aspects of the study, potentially affecting its relevance to the individual mother in front of you (e.g., the study population may not encompass the full spectrum of women with schizophrenia that you encounter in your practice, the medication exposure may not accurately reflect the frequency and dosage of antipsychotic medications taken in real-life scenarios, and hospitalization for psychosis may not be the desired outcome but rather something to be avoided).

Nevertheless, the findings from this study contribute another valuable piece to the puzzle of understanding the landscape of treatment options. Antipsychotic medications appear to play a role in reducing the risk of relapse in pregnant women diagnosed with schizophrenia. The consequences of a psychotic relapse during pregnancy are severe, including adverse obstetric outcomes as well as potential harm to oneself and others. If a relapse continues postpartum, it can significantly impact the mother-baby relationship. It is crucial to note that a healthy mother offers her child the best chance to thrive. While we must acknowledge that a comprehensive understanding requires further research, this study provides additional insights that may be beneficial in clinical discussions.

Potential Conflicts of Interest

Shuichi serves on the editorial board of the British Journal of Psychiatry, where the primary paper was published. He did not participate in the review or editing processes of the paper.

Key References for Further Reading

Primary Research Article

Kang K, Yang J, Yun B et al (2025) Antipsychotic Continuation during Pregnancy and Risk of Postpartum Relapse in Women with Schizophrenia: A Nationwide Register-Based Study. The British Journal of Psychiatry, 1 – 8.

https://www.cambridge.org/core/journals/the-british-journal-of-psychiatry/article/antipsychotic-continuation-during-pregnancy-and-risk-of-postpartum-relapse-in-women-with-schizophrenia-nationwide-registerbased-study/14FBE96D35D76307454A33AAD6F1CBF2

Additional References

Grzeskowiak L, Gilbert A, Morrison J. (2013) Methodological challenges in using routinely collected health data to investigate long-term effects of medication use during pregnancy. Therapeutic Advances in Drug Safety, 4(1), 27 – 37.
https://journals.sagepub.com/doi/10.1177/2042098612470389

Lefebvre A, Pouchon A, Bioulac S, et al (2022) Management of schizophrenia in women during the perinatal period: a synthesis of international recommendations. Expert Opinion on Pharmacotherapy, 23(11), 1337–1350. https://www.tandfonline.com/doi/full/10.1080/14656566.2022.2102421

Martin F. Psychotropic medication during pregnancy: new umbrella review finds no convincing evidence of adverse health outcomes for the baby, The Mental Elf, 18 Nov 2024.

Psychotropic medication during pregnancy: new umbrella review finds no convincing evidence of adverse health outcomes for the baby

Wallace J. Psychotropic medication in pregnancy: new evidence may help achieve a safe balance, The Mental Elf, 17 May 2016.

Psychotropic medication in pregnancy: new evidence may help achieve a safe balance

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