Clinical Psychopharmacology · Paper A
Antidepressants in pregnancy
Not all antidepressants in the same class carry identical risks in pregnancy. An SSRISelective serotonin reuptake inhibitor, a common type of antidepressant.Read more → (selective serotonin reuptake inhibitor) is a common antidepressant class, but individual drugs within it differ sharply in their pregnancy safety profile. Two women each prescribed an SSRI, e.g. one on paroxetine and one on sertraline, can face quite different risks despite being on the 'same' drug class. Clinically, the specific drug named in a question, not just the drug class, usually determines the correct answer.
Paroxetine, an SSRISelective serotonin reuptake inhibitor, a common type of antidepressant.Read more →, is the antidepressant most strongly linked to neonatal discontinuation symptoms, i.e. jitteriness, irritability, poor feeding, and breathing difficulty, when taken in late pregnancy, and to a small increase in cardiac septal defects (holes in the heart's dividing wall) when taken in the first trimester. Sertraline is generally regarded as a comparatively safer SSRI choice in both pregnancy and breastfeeding. Third-trimester SSRI exposure of any kind also carries a small risk of persistent pulmonary hypertension of the newborn (PPHN), a serious breathing problem in the baby. A woman switched from paroxetine to sertraline early in pregnancy, e.g. after a routine antenatal review flags the paroxetine prescription, shows how drug choice within a class can be adjusted to reduce risk. In practice, treatment decisions must weigh the risk of untreated depression relapse against these drug-related risks.
Prescribing an antidepressant during pregnancy is one of the most common real-world dilemmas in perinatal psychiatry, and it is a favourite exam topic because it forces you to weigh two competing harms rather than pick an obviously safe answer. The first harm is the risk of untreated or undertreated depression itself, which can cause poor antenatal engagement, poor nutrition, and an increased risk of postnatal depression and impaired bonding. The second harm is the direct risk of the medication to the developing fetus and newborn.
This topic is really about a single recurring clinical decision: for a pregnant woman with depression, does the balance of risk favour starting, continuing, switching, or stopping an antidepressant, and if a drug is used, which one. NICE CG192 (the National Institute for Health and Care Excellence guideline on antenatal and postnatal mental health) is the key UK guideline body governing this decision, alongside the BNF (British National Formulary, the standard UK drug reference) and the Maudsley Prescribing Guidelines for more complex cases.
A common beginner mistake is treating "SSRI" (selective serotonin reuptake inhibitor, a class of antidepressant that blocks the reuptake of serotonin at the ) as if every drug in the class carries identical risk in pregnancy. It does not. For example, two women each prescribed "an SSRI" during pregnancy can face quite different risk profiles depending on which specific drug they are taking, so exam stems that name a specific drug are usually testing knowledge of that drug's particular risk, not generic SSRI risk.
Paroxetine is the most strongly associated with two distinct, well-documented risks. First, when taken in the first trimester (the first three months of pregnancy, when the fetal heart is forming), paroxetine is linked to a small but real increase in cardiac septal defects, meaning holes in the wall dividing the chambers of the heart. Second, when taken in late pregnancy, paroxetine is linked to neonatal discontinuation symptoms in the newborn, including jitteriness, irritability, poor feeding, and breathing difficulty, thought to reflect the baby adjusting after birth to the sudden loss of the drug it was exposed to in utero. Sertraline, by contrast, is generally regarded as the comparatively safer SSRI in both pregnancy and breastfeeding, and its levels in breast milk are low. One risk is not specific to any single drug: any SSRI taken in the third trimester (the final three months of pregnancy) carries a small increased risk of persistent pulmonary hypertension of the newborn (PPHN, a serious condition in which the blood vessels in the newborn's lungs fail to relax normally after birth, causing dangerously low oxygen levels).
Suppose a woman with a history of severe depressive relapse after previously stopping antidepressants, for instance someone who became acutely unwell and required hospital admission the last time she came off medication, becomes pregnant while well on sertraline. Working through the decision step by step: her relapse risk if she stops treatment is high and well-documented from her own history; her drug-specific risk if she continues sertraline is comparatively low, since sertraline lacks paroxetine's cardiac signal; and the class-wide PPHN risk from continuing into the third trimester is small in absolute terms. Put together, continuing a comparatively lower-risk through pregnancy, with review at each trimester as the relevant risks change, will usually outweigh stopping treatment outright. Cardiac risk matters most in the first trimester; PPHN and neonatal adaptation symptoms matter most in the third.
This decision is easily confused with two related but distinct scenarios. It is not the same question as prescribing in breastfeeding alone, where the relevant risk is drug transfer into breast milk rather than fetal organogenesis or PPHN, though sertraline happens to be preferred in both settings for different reasons. It is also not the same as managing a first presentation of severe perinatal depression with psychotic features, which is a psychiatric emergency requiring urgent specialist perinatal mental health input and, potentially, admission, rather than a routine primary-care medication discussion. Recognising which of these three scenarios a stem is describing determines which risk-benefit calculation actually applies.
NICE CG192 recommends routine screening for depression at antenatal booking, using validated screening questions such as the Whooley questions, with a positive screen prompting further assessment. Diagnosis of a depressive episode itself still rests on standard ICD-11 or DSM-5 diagnostic criteria applied in the same way as outside pregnancy; pregnancy does not create a separate diagnostic category, only a separate treatment calculation once the diagnosis is made.
In practice, the clinical decision is never simply "stop the drug to protect the baby" or "continue the drug regardless." Sertraline is often the first-choice antidepressant reached for in pregnancy, or the drug clinicians switch a woman to from paroxetine once pregnancy is confirmed or planned, precisely because its risk profile is more favourable. Management follows NICE CG192, individualised to the woman, discussed collaboratively with her, and reviewed at each trimester as the balance of relapse risk against medication risk shifts.
Exam stems often name a specific and a specific trimester, expecting you to match the drug and timing to the correct risk: paroxetine plus first trimester should trigger cardiac defect risk, any SSRI plus third trimester should trigger PPHN and neonatal adaptation symptoms, and a woman with a severe relapse history should trigger the relapse-versus-medication-risk discussion rather than a reflex "stop all medication" answer.
The pregnancy antidepressant decision is never "drug versus no drug" but a trimester-specific, drug-specific weighing of relapse risk against medication risk, with paroxetine avoided for its first-trimester cardiac signal, sertraline generally preferred, and any carrying a small third-trimester PPHN risk.