Bupropion in Pregnancy Lactation: Evidence, Risk–Benefit, and Shared Decision-Making

Bupropion Overview: Indications, Side Effect Profile, How It Differs from SSRIs/SNRIs

Bupropion is approved for major depressive disorder (MDD), seasonal affective disorder (SAD), and as a pharmacologic aid for smoking cessation in pregnancy (Wellbutrin for Smoking Cessation). Off-label, it is sometimes used for attention deficit hyperactivity disorder and antidepressant-induced sexual dysfunction (Off-Label Powerhouse for Rekindling Libido and Treating ADHD Without Stimulants). Its therapeutic action is mediated mainly through inhibition of norepinephrine and dopamine reuptake, with negligible serotonergic activity. This pharmacologic profile gives bupropion a distinct side effect pattern compared with SSRIs and SNRIs. It is generally weight-neutral, associated with a low incidence of sexual side effects, and can have an activating effect, which may improve fatigue or hypersomnia. However, these same stimulating properties can also contribute to insomnia, anxiety, and restlessness in sensitive patients. The most serious dose-dependent risk is seizures, especially in individuals with eating disorders, alcohol withdrawal, or other predisposing conditions.

Compared to SSRIs and SNRIs, bupropion lacks serotonergic withdrawal phenomena but may not be as effective for anxiety-predominant depression. In pregnancy, it offers a potential alternative when SSRIs are poorly tolerated, ineffective, or contraindicated, particularly in the setting of comorbid nicotine dependence, where it can address both mood symptoms and smoking cessation.

Bupropion offers a potential alternative in pregnancy when SSRIs are unsuitable, particularly in women with comorbid nicotine dependence.

Bupropion Preconception: Assessing the Need for Therapy Before Conception

When planning a pregnancy, the decision to start, stop, or continue bupropion should begin with a clear assessment of the underlying condition. For patients with recurrent major depressive disorder or significant nicotine dependence, the risks of untreated illness, including relapse, functional impairment, and harmful health behaviors, may outweigh the potential but uncertain fetal risks of medication exposure.

Preconception counseling should include a comprehensive psychiatric and medical history, prior treatment responses, and documented episodes of relapse following medication discontinuation. If bupropion has been the only effective or well-tolerated option, maintaining therapy may be preferable to switching, provided the patient is informed about the current evidence base. For those with mild or well-controlled symptoms, a gradual taper before conception might be considered, with a plan for rapid re-initiation if relapse occurs. In smokers planning pregnancy, the dual benefit of bupropion for mood stabilization and risk–benefit analysis of tobacco cessation can be a compelling reason to continue treatment, given the established harms of prenatal tobacco exposure.

Ideally, the preconception phase allows for dose optimization, addressing comorbidities, and modifying other medications that might interact with bupropion metabolism. Collaboration between psychiatry, obstetrics, and, if relevant, smoking cessation specialists strengthens the care plan and facilitates shared decision-making, ensuring that patient values and priorities are fully integrated into the treatment choice.

The decision to continue or stop bupropion before conception requires weighing relapse risks against limited fetal safety data.

Bupropion in Pregnancy: Evidence on Congenital Anomalies, Miscarriages, Fetal Growth

The safety profile of bupropion during pregnancy has been investigated through cohort studies, pregnancy registries, and retrospective analyses. While the overall data suggest no major increase in the rate of congenital malformations, the evidence base is smaller than for SSRIs, and certain findings warrant closer scrutiny.

Large observational studies, including data from the Bupropion Pregnancy Registry, have not demonstrated a statistically significant increase in overall birth defect rates compared with the general population. However, some reports have noted a possible association with specific cardiac malformations, particularly left outflow tract heart defects. These findings are inconsistent across studies, and absolute risk, if present, appears to be low.

Regarding miscarriage risk, available studies do not indicate a clear causal link between bupropion exposure and spontaneous abortion, though sample sizes have been limited. Similarly, most data suggest no significant effect on fetal growth or preterm birth rates, but confounding factors such as maternal smoking can complicate interpretation.

A key limitation of existing studies is the difficulty separating the effects of bupropion from those of nicotine dependence, psychiatric illness, and other co-exposures. For example, women taking bupropion for smoking cessation may already have higher baseline risks related to tobacco use. Overall, the current evidence supports cautious but considered use of bupropion in pregnancy when benefits are expected to outweigh potential risks, especially in cases where untreated depression or ongoing tobacco use poses substantial harm to both mother and fetus. Continuous monitoring and individualized counseling remain essential components of care.

Overall evidence suggests no major increase in malformation risk, though some studies raise concern about specific congenital anomalies.

Bupropion vs Alternatives: Switching or Maintaining Therapy; Role of Comorbid Tobacco Dependence

When weighing bupropion against SSRIs or SNRIs during pregnancy, comparative safety data play a central role. SSRIs, particularly sertraline, have the largest pregnancy safety database, with generally reassuring findings for overall malformation risk. SNRIs, such as venlafaxine, have moderately less data but are still better studied than bupropion. For this reason, SSRIs are often considered first-line for antenatal depression.

Bupropion may be favored when the patient has previous non-response or intolerance to serotonergic antidepressants, a predominantly anergic or fatigue-driven depression, or coexisting nicotine dependence. In the latter case, bupropion’s efficacy in smoking cessation addresses two major risk factors simultaneously: maternal depression and prenatal tobacco exposure.

Switching from bupropion to an SSRI solely for pregnancy safety reasons should be approached with caution. Medication changes during pregnancy carry risks of destabilization, and relapse can have profound consequences for both maternal and fetal health. Switching is more reasonable if the patient has mild symptoms, no history of relapse after discontinuation, or if new safety data suggest a clear advantage for the alternative drug.

In nicotine-dependent patients, the benefit of smoking cessation, both in reducing fetal hypoxia and lowering the risk of low birth weight, can tip the balance in favor of maintaining bupropion, particularly if prior quit attempts with nonpharmacologic methods have failed.

SSRIs are usually first-line in pregnancy, but bupropion may be favored in cases of poor SSRI tolerance or coexisting tobacco dependence.

Bupropion Dosing Monitoring in Pregnancy

Pregnancy induces a range of physiological changes that can alter drug absorption, distribution, metabolism, and elimination. For bupropion, the most relevant changes occur in hepatic metabolism, plasma protein binding, and renal clearance of metabolites. Bupropion is extensively metabolized in the liver, primarily by CYP2B6 to hydroxybupropion. Data suggest that pregnancy may modestly increase CYP2B6 activity in some women, potentially leading to lower parent drug concentrations but higher metabolite exposure. This shift can have two consequences: first, reduced stimulation from the parent drug in those who respond more to bupropion itself, and second, increased risk of insomnia or restlessness in individuals sensitive to hydroxybupropion’s activating effects. However, the degree of change varies widely, and not all patients require dose adjustments.

For most pregnant patients, starting with the lowest effective dose and titrating cautiously remains the safest strategy. If dose escalation is necessary, the sustained-release (SR) or extended-release (XL) formulations are preferred over immediate-release forms to minimize peak-related side effects and reduce seizure risk. Monitoring should address both maternal and fetal well-being. On the maternal side, clinicians should track mood symptoms, sleep quality, appetite, and any emerging side effects such as tremor, agitation, or gastrointestinal discomfort. On the fetal side, standard obstetric monitoring — including ultrasound assessment of growth and well-being — should continue as clinically indicated.

In complex cases, particularly when other psychotropics are involved, therapeutic drug monitoring (TDM) can help assess whether bupropion or hydroxybupropion levels are unusually high or low. While TDM is not standard for all pregnant patients, it may be useful if there is poor response, unexpected side effects, or suspicion of drug–drug interactions.

Coordination between psychiatry, obstetrics, and, if applicable, smoking cessation specialists is essential. Documenting dose changes, rationale, and patient preferences in the medical record supports continuity of care and informed decision-making.

Ultimately, dosing in pregnancy should be individualized — balancing the need to maintain psychiatric stability and/or smoking abstinence against the principle of using the minimal effective exposure to achieve those goals.

Pregnancy can alter bupropion metabolism, so individualized dosing and careful maternal–fetal monitoring are essential.

These considerations specifically include potential CYP2B6 metabolism changes that may shift the balance between parent drug and metabolite exposure. (How CYP2B6 Variants and Hydroxybupropion Levels Can Personalize Care)

Bupropion Lactation: Transfer to Milk, Infant Monitoring, When to Avoid or Tolerate

Bupropion in lactation passes into breast milk in low to moderate amounts, with most studies estimating a milk-to-plasma ratio of less than 1. Measured infant serum concentrations are typically undetectable or very low, suggesting minimal direct exposure. However, isolated reports have described possible adverse effects, including irritability, poor feeding, and, in two cases, seizures in breastfed infants whose mothers were taking bupropion, though causality was not definitively established.

Current evidence, including LactMed and small pharmacokinetic studies, generally supports that bupropion is compatible with breastfeeding for healthy, full-term infants when maternal benefits outweigh theoretical risks. Nonetheless, caution is warranted in premature or neurologically vulnerable infants, where even small exposures could have disproportionate effects.

When bupropion is continued during lactation, clinicians should advise mothers to practice infant monitoring for changes in feeding patterns, sleep, alertness, or unusual irritability. If concerns arise, temporary cessation of breastfeeding or a switch to an alternative antidepressant with more robust safety data in lactation, such as sertraline, may be considered.

Dose timing can also be adjusted to reduce exposure, for example by taking the medication immediately after the last feed before the infant’s longest sleep interval. This strategy may modestly lower peak concentrations in milk during active feeding periods.

Bupropion appears generally compatible with breastfeeding, though caution is advised in vulnerable infants.

Bupropion Documentation Consent

Clear and thorough documentation is essential when prescribing bupropion during pregnancy or lactation. The medical record should include a summary of the risk–benefit analysis discussion, covering the potential effects of untreated depression or tobacco dependence, known and uncertain safety data, and alternative treatment options. Patient values and preferences must be recorded to demonstrate shared decision-making.

An informed consent note should specify the intended dose, formulation, monitoring plan, and criteria for reassessment. Any changes in therapy, such as dose adjustments or switches, should be documented along with the rationale.

Where relevant, attach educational materials or decision aids provided to the patient. This not only supports clinical transparency but also reinforces trust. Comprehensive records ensure that all members of the care team (psychiatry, obstetrics, primary care) can align on the treatment plan and respond promptly if maternal or infant safety concerns emerge.

Clear documentation and informed consent ensure transparency and support shared decision-making during treatment.

Bupropion Postpartum: Relapse Prevention, Sleep, Compatibility with Other Drugs

The postpartum period is a time of high relapse risk for women with a history of major depression or tobacco dependence. Continuing bupropion during this phase can help maintain mood stability and support smoking abstinence, particularly when prior discontinuation has led to rapid symptom return, as part of Postpartum relapse prevention. However, the drug’s activating properties can sometimes worsen postpartum insomnia, especially when combined with the fragmented sleep of caring for a newborn. Dose timing earlier in the day and using extended-release formulations can mitigate this effect.

Drug–drug interactions require attention, as postpartum patients may receive analgesics, antibiotics, or other medications. CYP2B6 inhibitors or inducers can alter bupropion and hydroxybupropion levels, potentially impacting both efficacy and tolerability.

Regular follow-up in the first three months postpartum allows for adjustment of dose, monitoring of maternal mental health, and early detection of any infant-related concerns if breastfeeding continues.

Continuing bupropion postpartum can prevent relapse but requires attention to insomnia and drug interactions.

Bupropion Clinical Pathway

A structured pathway (Clinical pathway) ensures consistent, transparent, and patient-centered care when using bupropion during pregnancy and lactation.

Preconception: Begin with a comprehensive psychiatric and medical review, assessing the history of depression, tobacco use, and prior treatment responses. Discuss risks of untreated illness versus medication exposure, and consider dose optimization before conception.

Early Pregnancy: Confirm ongoing need for therapy. If bupropion remains the preferred option, select the lowest effective dose and document a shared decision-making discussion. Initiate or update a monitoring plan for maternal mood, side effects, and fetal well-being.

Mid–Late Pregnancy: Adjust dose only if clinically necessary, watching for signs of overstimulation or reduced efficacy. Continue routine obstetric monitoring, adding therapeutic drug monitoring in complex cases.

Lactation: Reassess risks and benefits for breastfeeding. If continuing bupropion, counsel on infant observation and possible dose timing strategies to reduce exposure.

Postpartum: Monitor closely for relapse, insomnia, or interaction risks with new medications. Maintain documentation of all changes and discussions.

For patients, a written summary of the plan, including when to seek urgent review, strengthens adherence, safety, and trust in the care process.

A structured pathway provides consistency and patient-centered care across preconception, pregnancy, lactation, and postpartum stages.

References

1. Alwan, S., Reefhuis, J., Rasmussen, S. A., Olney, R. S., & Friedman, J. M. (2010). Maternal use of bupropion and risk of congenital heart defects. American Journal of Obstetrics and Gynecology, 203(1), 52.e1–52.e6. https://doi.org/10.1016/j.ajog.2010.03.038
2. Anderson, K. N., Huybrechts, K. F., Hernández-Díaz, S., Mogun, H., & Cooper, W. O. (2020). Maternal use of specific antidepressant medications in early pregnancy and risk of birth defects: A US cohort study. JAMA Psychiatry, 77(10), 1008–1015. https://doi.org/10.1001/jamapsychiatry.2020.1613
3. Gallitelli, S. (2024). Depression treatment in pregnancy: Is it safe, or is it not? International Journal of Environmental Research and Public Health, 21(4), 404. https://doi.org/10.3390/ijerph21040404
4. MotherToBaby. (2024). Bupropion. In MotherToBaby Fact Sheets. National Library of Medicine. https://www.ncbi.nlm.nih.gov/books/NBK582611/
5. Eleftheriou, G., Kalpaka, A., Michailidou, E., & Dardiotis, E. (2024). Principles of medicine transfer from the mother to the infant through human milk. International Journal of Environmental Research and Public Health, 21(5), 551. https://doi.org/10.3390/ijerph21050551