Antidepressants During Pregnancy: Risks and Alternatives

The decision to take antidepressants during pregnancy always balances two sets of risks: the risks of the medications and the risks of untreated depression. Current guidelines emphasize that for a significant proportion of patients, the benefits of continuing effective therapy outweigh the potential harm of discontinuing it, especially in moderate-to-severe cases and those with a high risk of relapse. The key principle is individualization, shared decision-making, and reliance on medications with a well-established safety profile. [1]

Untreated depression is associated with an increased risk of treatment interruption for medical conditions, substance abuse, suicidal behavior, preterm birth, and postpartum depression. Therefore, "doing nothing" is also a choice with consequences, and it is far from always safer. Several organizations (ACOG, SMFM) clearly point out that fears surrounding antidepressants are often exaggerated compared to the actual, generally low absolute risks of adverse outcomes. [2]

For mild depression, non-drug approaches (psychotherapy, cognitive behavioral therapy, supportive programs) are initiated, and medications are considered when the effect is insufficient. For moderate to severe depression and relapses, it is preferable to continue successful therapy, especially if discontinuation previously resulted in deterioration. This is reflected in current clinical guidelines. [3]

Finally, technically correct management is crucial: do not discontinue abruptly, consider the gestational age and dosage, monitor obstetric and neonatal risks, and prepare a birth and postpartum plan (including breastfeeding) in advance. This reduces the likelihood of "unexpected" effects and makes treatment predictable. [4]

What Current Guidelines Say (and Why It Matters)

ACOG (2023) and updated positions of relevant societies recommend that if a pregnant woman is diagnosed with depression, she should receive treatment comparable in effectiveness to the standard for non-pregnant women. Selective serotonin reuptake inhibitors (SSRIs) are most often used as first-line treatment, with priority given to agents with the most extensive study (e.g., sertraline). The choice depends on the previous response to therapy and tolerability. [5]

The SMFM specifically emphasizes that the overall data do not show an increased risk of major birth defects from SSIs; the absolute risks of such events remain low. This does not mean "zero risk," but it sets the correct perspective: the potential risks of medications must be compared with the risks of untreated disease. [6]

The UK's NICE recommends screening, a stepped approach, and collaborative treatment planning. For mild forms, psychotherapy and self-help are recommended; for moderate and severe forms, individually tailored pharmacotherapy (usually SSRIs) with monitoring is recommended. Discontinuing an effective regimen without compelling reasons is not supported, as it carries a high risk of relapse. [7]

If medications are contraindicated, ineffective, or rapid control of severe symptoms (including high suicidal risk) is required, electroconvulsive therapy (ECT) is considered: recent reviews note its relative safety in pregnancy when managed multidisciplinary. This is a rare but important option. [8]

Table 1. When to consider antidepressants during pregnancy (summary)

Clinical situation	Recommendation-based approach
Mild depression, first episode	Psychotherapy, self-help; medications - if there is no effect. [9]
Moderate/severe depression or high risk of relapse	Continuation/initiation of SSRI with monitoring is preferred. [10]
Drug resistance/contraindications, suicide risk	Consider ECT at a specialized center. [11]
Interruption of a successfully running scheme	Not recommended due to high risk of recurrence.[12]

What is known about the risks of SRIs and SNRIs (and how to understand them)

The most common concerns relate to malformations. Large cohort studies and modern pooled analyses show that for SSRIs as a class, no significant increase in the risk of major congenital malformations has been identified, and the signals for individual molecules (e.g., paroxetine) are heterogeneous and small in absolute terms. In routine practice, sertraline is more often chosen for new initiation due to the volume of data and its tolerability profile. [13]

Late exposure to SSRIs/SNRIs may be associated with "newborn adaptation syndrome" (tremors, irritability, transient rapid breathing, and muscle tone disturbances)—usually mild and resolving without specific treatment. The incidence is estimated at ~10-30%, but in most infants, symptoms are short-lived and do not require intensive care. The team informs the neonatologist in advance of the mother's SSRI use. [14]

Another discussed risk is persistent pulmonary hypertension of the newborn (PPHN) with late exposure to SSRIs. Current meta-analyses indicate a small relative increase in risk, but the absolute numbers remain low (few cases per thousand births). This is an important but rare outcome; it does not preclude treatment if it is needed by the mother. [15]

Postpartum hemorrhage (impact on platelet function) is considered separately; the risk is low and depends on the clinical context. When preparing for labor and in the early postpartum period, the obstetric team simply includes this in the monitoring plan. Overall, the risk profile of SRIs/SNRIs is considered acceptable with appropriate monitoring. [16]

Table 2. Risks of SRI/SNRI exposure: How to read the numbers

Risk	What the data shows	Practical meaning
Major congenital defects	No increase is shown for the SSRI class; signals for individual molecules are small. [17]	Not a reason to automatically discontinue effective therapy.
Newborn adaptation syndrome	10-30%, usually mild, transient. [18]	Alert neonatologist; usually observation.
PPHN in late exposure	Small increase in relative risk; low absolute incidence.[19]	Not a reason for total cancellation; take into account in conversation.
Postpartum hemorrhage	Moderate increase in risk in individual studies.[20]	Plan obstetric tactics.

What happens if you stop taking an antidepressant when you become pregnant?

A classic prospective study in JAMA found that women with recurrent depression who discontinued treatment had a nearly five-fold higher risk of relapse during pregnancy than those who continued treatment (68% vs. 26%). This explains why many guidelines advise against "prophylactic" discontinuation of a successful regimen without compelling reasons. [21]

A relapse of depression is not only a worsening of mood. It also carries the risk of loss of function, neglect of self-care and pregnancy, poor nutrition and sleep, increased anxiety and unhealthy behavior, and even suicidal risk. These consequences have an indirect and direct impact on pregnancy outcomes and the well-being of the newborn. [22]

Therefore, a "gradual" withdrawal strategy, purely "just in case," is rarely justified. Moreover, attempts to "withdraw the medication in the first trimester and then reintroduce it" often result in a loss of symptom control and do not reduce the risks sufficiently to justify the deterioration. The decision is always made individually after assessing the patient's medical history and current severity. [23]

If discontinuation is indicated (intolerance, specific risks, patient preference), it should be done gradually, with a plan for alternatives (psychotherapy, other molecules, ECT) and frequent monitoring. Abrupt discontinuation is contraindicated due to the risk of exacerbation and withdrawal syndrome. [24]

Table 3. Risks of untreated depression for mother and fetus

Consequences of untreated depression	Why is this important?
High risk of relapse/worsening	Loss of control over symptoms, deterioration of self-care. [25]
Preterm birth/low birth weight (associations)	Through stress, behavioral and biological mechanisms. [26]
Postpartum depression	Decreased quality of child care, difficulties with breastfeeding. [27]
Suicidal risk, substance abuse	Highest in withdrawal without a plan and severe depression. [28]

Which antidepressants are used most often (and why)

Sertraline is one of the most studied SRIs during pregnancy and lactation; most studies have shown no increase in the risk of major malformations. It is often considered a first-line drug when initiating pregnancy. [29]

SNRIs (venlafaxine, duloxetine) can be used when indicated, especially if they have previously provided remission. The risk profile is similar to that of SSRIs: neonatal adaptation is possible and PPHN is rare with late exposure; absolute risks are low. The choice depends on the history of efficacy. [30]

Bupropion is an option for patients who are ineffective or intolerant to SSRIs/SNRIs, as well as for those quitting smoking. Data on birth defects are generally reassuring: large cohorts and reviews have not found an increase in overall risks compared with other antidepressants. The decision is made by a physician, taking into account the clinical situation. [31]

Mirtazapine is an alternative for nausea/loss of appetite and sleep disturbances; recent systematic reviews find no convincing evidence of major risks beyond the expected adaptation syndrome. The quality of the evidence is moderate, but clinically, it is a viable option in cases of resistance. [32]

Table 4. Frequently used antidepressants during pregnancy

Class/drug	What the data says	When to choose
SSRI (sertraline, etc.)	Well studied; low absolute risks of serious outcomes. [33]	First line at initiation/continuation.
SNRIs (venlafaxine, duloxetine)	The risk profile is similar to the SSRI. [34]	If remission was previously achieved.
Bupropion	No increase in risk of major malformations in cohorts.[35]	An alternative, including when quitting smoking.
Mirtazapine	There is less data, but no convincing signals of major risks. [36]	In case of severe nausea/poor sleep, resistance.

How to put it into practice: a step-by-step, “no drama” plan

Step 1. Assess severity: using validated scales (e.g., PHQ-9/EPDS), history of relapse, suicidal ideation, and concomitant diagnoses. For mild forms, psychotherapy; for moderate to severe forms, discuss pharmacotherapy. The plan is documented in writing. [37]

Step 2. If the woman is already taking an antidepressant and it's working, don't automatically stop. Discuss the risks and benefits, taking into account the timing, dosage, and previous experience. If switching to a more well-studied medication is chosen, do so gradually, with overlapping (cross-titration) and observation. [38]

Step 3. In case of late exposure, alert neonatologists to the possibility of short-term adaptation in the newborn. This is not a reason to discontinue treatment immediately before delivery: abrupt discontinuation increases the risk of relapse and worsens outcomes. It is better to schedule observation of the child. [39]

Step 4. If drug therapy is not possible/sufficient, consider ECT in a specialized center, especially in cases of severe, treatment-resistant depression, psychosis, or high suicidal risk. This helps minimize overall exposure to psychotropic medications. [40]

Table 5. Mini-algorithm for choosing tactics

Starting situation	What to usually do
Mild depression, first line	Psychotherapy, monitoring, escalation plan. [41]
Moderate/severe depression	Continue/start SSRI with monitoring. [42]
Resistance/side effects	Consider SNRIs, bupropion, or mirtazapine.[43]
High risk, contraindications	ECT in an experimental center. [44]

Special issues: breastfeeding, postpartum period and "new" drugs

Sertraline and paroxetine have the best profile for breastfeeding (low concentrations in milk; minimal clinical effects in infants). In most cases, continuation of SSRIs is compatible with breastfeeding and is preferable to discontinuation if there is a risk of relapse in the mother. The strategy is agreed upon with the pediatrician and takes into account the child's clinical condition. [45]

Postpartum depression requires active management. In recent years, neurosteroids (brexalone/zurenalone) have been approved for the treatment of postpartum depression, but they are not used during pregnancy: the instructions emphasize potential harm to the fetus, and data from pregnant women are insufficient. Their role is strictly postpartum, as indicated. [46]

If breastfeeding is planned, the regimen is selected based on lactation status; abruptly changing an effective medication "before delivery" is usually unnecessary. It is more important to establish monitoring, arrange support (family, breastfeeding consultant), and discuss a plan in advance in case of symptom exacerbation. This reduces the likelihood of treatment interruptions and breastfeeding failure. [47]

If a newborn shows signs of adaptation (drowsiness/tremors/rapid breathing), observation is usually sufficient; in most children, symptoms subside quickly. If symptoms are prolonged or severe, the neonatologist will determine the appropriate course of action; a connection with the drug is not always confirmed. [48]

Table 6. Antidepressants and breastfeeding (quick guide)

Preparation	Compatibility with breastfeeding (general)	Comments
Sertraline	Preferred	Low levels in milk; good observational experience. [49]
Paroxetine	Let's assume	Alternative if well tolerated by the mother. [50]
Venlafaxine/duloxetine	Acceptable according to indications	Clinical monitoring of the infant is required.[51]
Bupropion/Mirtazapine	Possible depending on indications	Less data; decision is individual. [52]

Safety at every stage and red flags for urgent treatment

In the first trimester, the primary concern is malformations. For SSRIs, there is generally no significant increase in risk; if a new molecule can be selected, sertraline is most often used. If pregnancy occurs while using another SSRI and it is effective, automatic switching is not necessary. The mother's stability is more important. [53]

In the second and third trimesters, the emphasis shifts to obstetric management and preparation for birth, including informing neonatologists about possible adaptations. Abrupt discontinuation before birth is not recommended, as it increases the risk of relapse. If dosage adjustments are necessary, they are based on clinical judgment, not the "trimester rules." [54]

Red flags for immediate treatment include: suicidal thoughts and plans, a sharp worsening of depression or anxiety, psychotic symptoms, refusal to eat or drink, dehydration, insomnia with severe exhaustion, and failure to respond to initial treatment. In these situations, delay is dangerous – crisis services and/or hospitalization are called in. [55]

Any decisions about changing therapy during pregnancy and the early postpartum period should be made only in consultation with a doctor. Online advice and unauthorized "switching" of medications increase the risks for both mother and child. [56]

Table 7. What to discuss with your doctor before making a decision

Question	For what
"What is my severity of depression and risk of relapse?"	Determine if the drug is needed now. [57]
"Which molecules are best based on my medical history?"	Maintain remission and reduce risks. [58]
"What is the plan for labor and the first weeks?"	Train neonatologists and support team. [59]
"Compatible with breastfeeding?"	Coordinate treatment and breastfeeding, reduce anxiety. [60]

Brief conclusions

1. For most pregnant women with depression, it is appropriate to continue or initiate treatment if clinically indicated: SSRIs are the first line; sertraline is one of the most studied options. The decision is individualized. [61]
2. Absolute risks of serious drug-related outcomes are low; neonatal adaptation syndrome is often mild and transient; PPHN is a rare outcome. Untreated depression carries comparable or greater risks. [62]
3. Antidepressants should not be discontinued abruptly upon pregnancy, as the risk of relapse is high. Any changes should be made gradually, with a plan and monitoring. [63]
4. For breastfeeding, sertraline/paroxetine are preferred; postpartum neurosteroids (zurenalone, etc.) are not used during pregnancy. [64]