Chapter 7 Pregnancy and Breastfeeding
Drug Choice in Pregnancy High Yield
Severe mental illness (SMI) is associated with an increased risk of obstetric near misses (life-threatening obstetric complications) [1]. The perceived association (or lack thereof) between specific drugs and adverse outcomes can change over time as more information is gathered and analysed [1].
ACOG Warning: Do Not Withhold Treatment
The ACOG warns against withholding or discontinuing medications for mental health conditions solely because of pregnancy or lactation status [1].
General Principles of Prescribing in Pregnancy
In all women of child-bearing potential:
- Topiramate is added to the list of drugs (alongside valproate and carbamazepine) generally contraindicated during pregnancy [1].
Table 1: Contraindicated Drugs & Contraceptive Requirements
| Medication Name | Status in Pregnancy | Action Required if Planning Pregnancy | Risk Tier |
|---|---|---|---|
| Valproate | Contraindicated (Highest Risk) | Stop immediately / transition pre-conception. Folic acid [1]. | |
| Carbamazepine | Generally Contraindicated | Discuss stopping. Consider low-dose monotherapy if essential [1]. | |
| Topiramate | Generally Contraindicated | Transition to safer alternatives. Ensure contraception [1]. |
Contraindicated Drugs & Contraception
Valproate, carbamazepine, and topiramate are generally contraindicated in pregnancy due to significant risks [1].
If use of these drugs is absolutely unavoidable, the prescriber must confirm the presence of an effective and stable long-term contraceptive plan [1].
- If use of these contraindicated drugs is unavoidable, the prescriber must confirm the presence of an effective and stable long-term contraceptive plan [1].
If mental illness is newly diagnosed in a pregnant woman:
- Consider non-pharmacological interventions first [1].
- Review the current medication regimen to ensure there is a clear indication for each drug and stop any ineffective drugs [1].
If a woman taking psychotropic drugs is planning a pregnancy:
- Discontinuation consideration should occur after a careful review of her history [1].
- Be aware that drug-induced hyperprolactinaemia may prevent pregnancy; consider switching to an alternative drug if this occurs and pregnancy is planned [1].
- For women with Severe Mental Illness (SMI), pre-conception advice from a perinatal psychiatrist should be sought to discuss relapse risk and a prospective perinatal care plan [1].
If a woman taking psychotropic medication discovers that she is pregnant:
Immediate Action: Valproate
If a woman taking valproate (as a mood stabiliser) discovers she is pregnant, it must be stopped immediately due to high teratogenic risk [1].
- Valproate (if prescribed as a mood stabiliser) must be stopped immediately [1].
- Early pregnancy can involve noticeable mood changes, potentially requiring a review of the medication plan to ensure symptoms remain well controlled [1].
Clinical Example: Pre-Conception Management
A 29-year-old woman with bipolar disorder is currently taking valproate [1]. In consultation with a perinatal psychiatrist, she is seeking pre-conception advice to design a perinatal care plan and safely transition to alternative therapies [1].
If the patient smokes:
Smoking, Vaping & NRT
Vaping is probably safer than tobacco smoking but is not without risk. Nicotine replacement therapy (NRT) is probably safer than vaping [1].
- Vaping is probably safer than tobacco smoking but is not without risk. Nicotine replacement therapy (NRT) is probably safer than vaping [1].
In all pregnant women:
- Hepatic enzyme activity changes markedly during pregnancy (in addition to previously mentioned CYP changes) [1].
- For patients with SMI, specifically discuss referral to specialist perinatal services [1].
- Ensure adequate fetal screening through liaison with obstetric services [1].
- Inform the obstetric team and, where appropriate, liaise with the neonatology team about psychotropic use and potential complications [1].
- Documentation should include the plan for medication [1].
Which of the following anticonvulsants/mood stabilizers has been newly added to the list of contraindicated medications in pregnancy for women of child-bearing potential alongside valproate and carbamazepine?
Correct Answer (C): According to the provided text: "In all women of child-bearing potential: Topiramate is added to the list of drugs (alongside valproate and carbamazepine) generally contraindicated during pregnancy." [1] The other options do not carry the same general contraindication status outlined under general principles of prescribing in pregnancy [1].
Psychosis During Pregnancy and Postpartum High Yield
High Risk of Postpartum Psychosis
The risk of postpartum psychosis for women with a previous episode, a diagnosis of bipolar disorder type 1 or schizoaffective disorder, and genetic loading for these conditions can be as high as 50% [1].
The risk of postpartum psychosis for women with a previous episode, a diagnosis of bipolar disorder type 1 or schizoaffective disorder, and genetic loading for these conditions can be as high as 50% [1].
Visualization: Postpartum Psychosis Risk Profiles
First-Generation Antipsychotics (FGAs)
- While specific malformations have been reported with individual agents, FGAs are unlikely to be major teratogens overall [1].
- A 2023 study covering nearly 6.5 million women confirmed that antipsychotics (including 6371 prescribed an FGA) were not major teratogens [1]. However, it noted an observed increased risk of cardiac malformations with chlorprothixene, suggested as a safety signal for further study [1].
- The potential association between haloperidol and limb defects has not been replicated in larger studies [1].
- An increased risk of gestational diabetes has been reported with FGAs [1].
- A higher risk of postpartum bleeding during vaginal delivery and a higher placenta-to-birth weight ratio have been reported [1].
- An increased risk (especially with late pregnancy exposure) of neonatal withdrawal symptoms, neurological disorders, and persistent pulmonary hypertension has been reported, although the absolute risk is low and effects seem predominantly mild and transient [1].
- Prolonged neonatal hospital stay after birth has been reported [1].
Second-Generation Antipsychotics (SGAs)
- While specific malformations have been reported with individual agents, SGAs are unlikely to be major teratogens overall [1].
- The 2023 study (including 21,751 prescribed an SGA) also reported that antipsychotics were not major teratogens [1]. It noted observed increased risks (viewed as safety signals) for oral clefts with olanzapine, and gastroschisis and brain anomalies with all SGAs [1].
- Available data suggest lurasidone is not a major teratogen [1].
- Neonatal seizures may be more likely with clozapine compared to other SGAs [1].
Clinical Example: Clozapine Management and Smoking Cessation
A 31-year-old pregnant woman with treatment-resistant schizophrenia is maintained on clozapine [1]. Upon discovering her pregnancy, she abruptly stops smoking. The clinical team monitors her plasma levels closely to prevent toxic rebound, as smoking cessation removes CYP1A2 induction [1].
Clozapine in Pregnancy
On the balance of evidence, clozapine should usually be continued during pregnancy. Clozapine plasma level monitoring may be beneficial, especially if the patient's smoking habits change (smoking induces clozapine metabolism) [1].
- On the balance of evidence, clozapine should usually be continued during pregnancy. Clozapine plasma level monitoring may be beneficial, especially if the patient's smoking habits change [1].
- The risk of gestational diabetes may be greatest with clozapine, olanzapine, and quetiapine [1].
- SGAs have also been associated with low birth weight and postpartum bleeding during vaginal delivery [1].
- Contradictory findings exist regarding metabolic risks: some studies report a lower risk with SGAs compared to FGAs, and others report no increased risk of metabolic complications [1].
- An increased risk (especially with late pregnancy exposure) of neonatal withdrawal symptoms, neurological disorders, and persistent pulmonary hypertension has been reported (similar to FGAs), with low absolute risk and predominantly mild/transient effects [1].
- Quetiapine demonstrates a relatively low rate of placental passage [1].
- A Finnish study (where quetiapine was the most used antipsychotic) showed a higher risk of increased postpartum bleeding in vaginal delivery, prolonged neonatal hospital stay, and a higher placenta-to-birth-weight ratio associated with antipsychotic use [1].
Avoid Cariprazine
The advice regarding cariprazine is strengthened: it should probably be avoided due to risks noted in animal studies [1].
- The advice regarding cariprazine is strengthened: it should probably be avoided due to risks noted in animal studies [1].
Visualization: Relative Placental Passage of Selected Antipsychotics
Antipsychotic Use and Longer-Term Neurodevelopment
- A small study of school-aged children showed no significant adverse effect on IQ or neurodevelopmental functioning following prenatal antipsychotic exposure [1].
- A large cohort study (n=667,517) did not show an association between maternal antipsychotic prescription and poorer standardized test performance (language, mathematics) in schoolchildren [1].
- Two large cohort studies reported an increased risk of ADHD and Autism Spectrum Disorder (ASD) associated with maternal mental illness itself, but not specifically with prenatal antipsychotic exposure [1].
- A smaller study reported no increased risk of psychiatric disorders in children born to women who continued antipsychotics during pregnancy [1].
- A 2022 birth cohort study found antipsychotics were not causally associated with neurodevelopmental disorders, although a safety signal for aripiprazole was noted, requiring further study [1].
Recommendations – Psychosis in Pregnancy
Risk of Untreated Illness
It's crucial to remember the high risk of adverse outcomes for both mother and child associated with untreated maternal illness. This risk must be weighed against potential medication risks [1].
- It's important to note the high risk of adverse outcomes for both mother and child associated with untreated maternal illness [1].
- When initiating an antipsychotic, consider using the one that has previously worked best for the woman (after discussing risks/benefits) [1].
- Be clear about the indication for each drug, use the lowest effective dose, prescribe as few drugs as possible (simultaneously and sequentially), and do not continue medication that is ineffective [1].
- The Australian Centre of Perinatal Excellence (COPE) recommends a 13- or 18–20-week ultrasound for women taking antipsychotics in the first trimester [1].
Neonatal Considerations (Late Pregnancy Antipsychotics)
- Antipsychotic discontinuation symptoms (e.g., crying, agitation, increased suckling) can occur in the neonate (class effect) [1].
- Recommendation: Women taking antipsychotics in late pregnancy should give birth in a unit with access to paediatric intensive care facilities [1].
- Some centres use mixed (breast/bottle) feeding to help minimize neonatal withdrawal symptoms [1].
- Antipsychotic discontinuation symptoms (e.g., crying, agitation, increased suckling) can occur in the neonate and are thought to be a class effect [1]. It is recommended that women taking antipsychotics in late pregnancy give birth in a unit with access to paediatric intensive care facilities [1].
- Some centres utilize mixed (breast/bottle) feeding to help minimize neonatal withdrawal symptoms [1].
Table 2: Antipsychotic Adverse Profiles in Pregnancy
| Medication Class / Drug | Reported Neonatal Risks / Safety Signals | Placental Passage / Safety Status | Severity Tier |
|---|---|---|---|
| Chlorprothixene | Observed increased risk of cardiac malformations (safety signal) [1] | FGA class risks (postpartum bleeding, etc.) [1] | |
| Clozapine | Gestational diabetes (highest risk), neonatal seizures [1] | Usually continued; monitor plasma levels [1] | |
| Quetiapine | Gestational diabetes, postpartum bleeding (Fin study) [1] | Relatively low rate of placental passage [1] | |
| Cariprazine | Risks noted in animal studies [1] | Should probably be avoided [1] |
Which second-generation antipsychotic demonstrates a relatively low rate of placental passage and is associated with a risk of gestational diabetes, yet remains a common consideration in pregnancy?
Correct Answer (A): The text specifically states: "Quetiapine demonstrates a relatively low rate of placental passage." [1] While clozapine and olanzapine are associated with gestational diabetes, they do not have the same noted low placental passage [1]. Cariprazine should probably be avoided entirely due to animal risks [1].
Antidepressants High Yield
Relapse rates are higher in those with a history of depression who discontinue medication compared with those who continue [1]. One study found that 68% of women who were well on antidepressant treatment and stopped during pregnancy relapsed, compared with 26% who continued antidepressants [1]. Risk is likely to be highest for women with a history of severe and/or recurrent depression [1]. The rate of antidepressant withdrawal will also influence the risk of depressive relapse [1]. Available data do not suggest an association between prenatal antidepressant use and neurodevelopmental disorders (after controlling for maternal illness and other confounders) [1]. There is also some evidence that successful antidepressant use can be beneficial for child behavioural outcomes [1]. A Danish study found that adverse outcomes were relatively more likely in depressed women not taking antidepressants [1]. However, antidepressant exposure in pregnancy may be an important marker of the need for early screening and intervention [1].
Visualization: Depressive Relapse Rates in Pregnant Women
Tricyclic Antidepressants (TCAs)
- Fetal exposure to tricyclics (via the umbilicus and amniotic fluid) is high [1].
- TCAs have been widely used throughout pregnancy without apparent detriment to the fetus [1].
- A weak association between clomipramine use and cardiovascular defects cannot be excluded [1]. The European SPC for Anafranil (branded clomipramine) does not recommend its use during pregnancy [1].
- The labels for other TCAs also contain a caution about withdrawal effects in neonates [1].
- One case of neonatal QT prolongation and torsades de pointes (clomipramine) and one case of Timothy syndrome (amitriptyline) have been reported [1].
- TCA use during pregnancy is associated with an increased risk of preterm delivery [1].
- Use of TCAs in the third trimester is well known to produce neonatal withdrawal effects (agitation, irritability, seizures, respiratory distress, etc.), usually mild and self-limiting [1].
- The authors of a study that reported an association between maternal antidepressant use and an increased risk of affective disorders in offspring suggested the observed associations may be attributable to underlying parental psychopathology [1].
- There are no convincing data suggesting an association between prenatal antidepressant use and neurodevelopmental disorders or ASD diagnoses or traits [1].
Selective Serotonin Reuptake Inhibitors (SSRIs)
- SSRIs appear not to be major teratogens [1].
- Regarding the reported association between prenatal SSRI use and congenital heart defects (possibly higher with fluoxetine/paroxetine in some studies), it is suggested that mood disorders alone may be the cause of any increased risk [1]. Fetal alcohol disorders (potentially linked to self-medication for depression) are also associated with cardiac defects [1].
- Sertraline appears to result in the least placental exposure [1].
- There may be a small increased risk of preterm birth, low birth weight, lower Apgar scores, and admission to neonatal intensive care units with SSRIs [1]. Maternal depression itself increases these risks [1].
- Poor neonatal adaptation (including withdrawal symptoms) has been reported [1]. Risk may be increased with prematurity and increasing dose, and may be higher with other SSRIs than sertraline [1].
- SSRIs may increase the risk for persistent pulmonary hypertension of the newborn (PPHN) [1]. The absolute risk appears small and may exist only in late pregnancy exposure, possibly lower with sertraline [1].
- Gestational hypertension, pre-eclampsia, placental abnormalities and postpartum haemorrhage have been reported with SSRI use (small risks; maternal depression itself increases these) [1].
MHRA Warning: Postpartum Haemorrhage
The UK MHRA advises awareness of a small increased risk of postpartum haemorrhage with SSRI/SNRI antidepressant use during the month before delivery [1].
- The UK MHRA advises awareness of the small increased risk of postpartum haemorrhage with SSRI/SNRI use during the month before delivery [1].
- A large 2022 cohort study reported that antidepressant use in pregnancy itself does not appear to increase the risk of neurodevelopmental disorders in children [1]. There is no reliable evidence indicating an increased risk of ADHD [1].
- Authors of studies reporting associations between antidepressant exposure and later affective/emotional disorders in offspring suggest these may be attributable to underlying parental psychopathology rather than direct in utero exposure [1].
- A 2023 study reported changes in brain morphology associated with SSRI exposure during pregnancy, persisting into adolescence [1]. The clinical significance is unclear as outcomes were not assessed [1].
Other Antidepressants
- Despite previous reports linking venlafaxine to specific birth defects, a 2022 meta-analysis concluded that available data do not indicate any SNRIs to be major teratogens [1].
- Venlafaxine has been associated with neonatal withdrawal/poor adaptation syndrome, small for gestational age babies, and postpartum haemorrhage [1].
- The UK MHRA advises awareness of the small increased risk of postpartum haemorrhage with SSRI/SNRI use during the month before delivery [1].
- SNRIs may be associated with an increased risk for persistent pulmonary hypertension of the newborn (PPHN) [1]. The absolute risk appears low [1].
- Duloxetine use may be associated with a small increase in postpartum hemorrhage risk [1]. A population study did not show an increased risk of major/minor malformations or stillbirth [1].
- A 2023 study found no significant difference in major congenital anomaly risk after first-trimester trazodone vs. SSRI exposure [1].
- Data for trazodone, bupropion (amfebutamone), and mirtazapine safety are limited [1].
- Regarding the link between bupropion/mirtazapine and spontaneous abortion, this might be attributable to underlying psychiatric disease [1]. A 2022 Danish study did not associate mirtazapine with major malformations, spontaneous abortion, stillbirth or neonatal death [1].
- First-trimester bupropion exposure may slightly elevate risk of ventricular septal defects [1]. In utero exposure has been associated with increased ADHD risk in young children [1].
- Limited data suggest absence of teratogenic potential with moclobemide and reboxetine [1].
- Monoamine oxidase inhibitors (MAOIs) should be avoided due to suspected increased risk of congenital malformations and risk of hypertensive crisis [1].
- Electroconvulsive therapy (ECT) is not known to cause harm to mother or fetus, though anaesthesia carries risks [1]. NICE recommends ECT for pregnant women with severe depression, severe mixed affective states, mania, or catatonia where physical health is at serious risk [1].
Recommendations – Depression in Pregnancy (Box 7.3 Updates)
- Patients already receiving antidepressants at high risk of relapse are best maintained on the same antidepressant (if effective/tolerated) during and after pregnancy [1].
First-Line Antidepressant Choice (ACOG/COPE)
ACOG recommends SSRIs first line (with SNRIs as reasonable alternatives). If no prior pharmacotherapy history, sertraline or escitalopram are reasonable first-line choices. COPE (Australia) also recommends SSRIs first line [1].
- ACOG recommends SSRIs first line (with SNRIs a reasonable alternative). If no pharmacotherapy history, sertraline or escitalopram is a reasonable first-line medication [1]. COPE recommends SSRIs first line [1].
- For moderate to severe perinatal depression with onset in the third trimester, ACOG recommends consideration of brexanolone [1].
- Screen for alcohol use and be vigilant for hypertension and pre-eclampsia [1].
- Women taking SSRIs or SNRIs late in pregnancy may be at increased risk of postpartum haemorrhage [1].
- The neonate may experience poor neonatal adaptation syndrome or discontinuation symptoms [1].
- NICE (UK) advises additional monitoring of the newborn of women who have taken an SSRI or SNRI during pregnancy [1].
Table 3: Antidepressant Comparative Risks
| Antidepressant Name | Placental Passage / Safe Choice | Specific Risks / Warnings | Risk Level |
|---|---|---|---|
| Sertraline | First-Line / Least placental exposure [1] | PPHN risk (low), neonate adaptation syndrome [1] | |
| Clomipramine | TCA / High fetal exposure [1] | QT prolongation, cardiovascular defects link [1] | |
| Venlafaxine | SNRI / No major teratogenicity [1] | Postpartum haemorrhage (MHRA warning), withdrawal [1] | |
| MAOIs | Contraindicated [1] | Hypertensive crisis, congenital malformations [1] |
According to the statistics cited in the text regarding antidepressant discontinuation, what is the relapse rate of pregnant women who discontinue their antidepressant compared to those who continue?
Correct Answer (B): The text states: "One study found that 68% of women who were well on antidepressant treatment and stopped during pregnancy relapsed, compared with 26% who continued antidepressants." [1] Discontinuing medication represents a significant threat to maternal mood stability [1].
Bipolar Illness During Pregnancy and Postpartum High Yield
The risk of relapse during pregnancy if mood-stabilising medication is discontinued is high, and the risk of relapse after delivery is hugely increased [1].
Risk vs. Benefit: Continuing Mood Stabilisers
The risks of not stabilising mood (e.g., need for hospital admission) must be weighed against medication risks [1].
For women with severe illness or rapid relapse history, continuing medication (except valproate) is often advised after risk discussion (ACOG recommendation) [1].
NICE UK prefers mood-stabilising antipsychotics over traditional mood stabilisers [1].
- The risks of not stabilising mood include the need for hospital admission [1].
Mood Stabilisers (Non-antipsychotics)
Lithium
- Lithium completely equilibrates across the placenta [1]. Use has been associated with increased risk of congenital anomalies (first trimester, possibly dose-related) [1]. While the risk of Ebstein's anomaly seems lower than previously thought, the overall risk exists [1].
- If continued, high-resolution ultrasound/echocardiography recommended (ACOG/COPE) [1].
- NICE suggests considering stopping gradually (if well) or switching/restarting later (if high risk/not well) [1]. If continuing lithium: Check levels frequently (every 4 weeks, then weekly from 36 weeks), maintain fluid balance, stop during labour, check levels 12hr post-last dose. Deliver in hospital [1].
- Lithium use in pregnancy associated with increased risk of spontaneous preterm birth and large for gestational age neonates (Note: A large cohort study reported no association with placenta-mediated complications or preterm birth) [1].
- May increase risk of neonatal readmission within 4 weeks postpartum (conflicting data) [1].
- Neonatal goitre, hypotonia, lethargy, cardiac arrhythmia, respiratory symptoms, and low Apgar scores have been reported [1].
- Lithium probably does not affect neonatal brain development [1].
Valproate
Valproate - STRONGLY CONTRAINDICATED
High risk (around 10%) of major malformations (neural tube defects, cardiac defects, cleft palate, hypospadias, etc.) [1].
Clear causal link to motor and neurodevelopmental problems (up to 40% delay, lower IQ, ASD) [1].
Should NOT be used in women of child-bearing potential unless ALL other treatments failed AND effective long-term contraception is in place (UK: requires agreement of 2 specialists for under 55s) [1].
Must be discontinued before pregnancy (NICE, ACOG, COPE). Stop over 2-4 weeks when planning conception, add high-dose folic acid (COPE) [1].
It is difficult to imagine any situation where benefits outweigh the huge risks in pregnancy [1].
- Valproate should not be used in women of child-bearing age except where all other treatment has failed and when there is a long-term effective contraception plan [1]. It must be stopped before pregnancy [1].
- Confers a high risk (~10%) of major malformations (esp. neural tube defects) and significant neurodevelopmental problems (delays, lower IQ, ASD) [1].
- UK: Use in women of child-bearing potential requires agreement of two specialists if under 55 and no other effective/tolerated treatment exists [1].
- Difficult to justify use in pregnancy given the risks [1].
- May increase risk of pre-eclampsia [1].
Visualization: Valproate Teratogenicity & Neurodevelopmental Risk Profile
Carbamazepine
- Clear causal link with fetal abnormalities (esp. neural tube defects). Risk lower than valproate but still significant [1].
- NICE advises not to offer for mental health problems if planning pregnancy/pregnant/breastfeeding [1]. Discuss stopping if already taking [1].
- If essential, use low-dose monotherapy [1]. May necessitate maternal vitamin K in third trimester [1].
- Lower Apgar scores reported (low absolute risk) [1].
Lamotrigine
- Growing evidence suggests it is safer than carbamazepine or valproate [1]. Risk of major malformations appears similar to unexposed children [1].
- Clearance increases radically during pregnancy and reduces postpartum; frequent level monitoring necessary (NICE) [1].
- Some reports of behaviour problems or increased ASD risk, but overall effect on neurodevelopment appears not significant [1].
- Option for bipolar depression in pregnancy [1].
Topiramate
Topiramate - CONTRAINDICATED
Associated with major malformations (specifically orofacial clefts) [1].
Increased risk of neurodevelopmental disorders and small for gestational age reported [1].
Should not be used in pregnant women. Women of child-bearing age must use effective contraception [1].
- Associated with major malformations (esp. orofacial clefts) and increased risk of neurodevelopmental disorders and small for gestational age [1].
- Should not be used in pregnant women. Women of child-bearing age should take precautions to avoid pregnancy [1].
- Lower Apgar scores reported (low absolute risk) [1].
Oxcarbazepine
- Data are unclear [1]. A 2022 meta-analysis reported a small, non-significant increased risk of malformations [1].
- Some studies reported an association with fetal/perinatal deaths [1].
- Difficult to draw firm conclusions due to study limitations [1].
Pregabalin
- Data are unclear [1].
- Based on a Nordic study showing a small increased risk of major malformations (vs. lamotrigine/duloxetine), UK MHRA/manufacturers advise awareness of risk and use of effective contraception [1].
Note on Folate
- No evidence it protects against anticonvulsant-induced neural tube defects *if given during* pregnancy, but may if given *prior* to conception [1]. Should always be offered as may benefit early neurodevelopment [1].
- A large cohort study reported anticonvulsant mood stabilisers were not associated with placenta-mediated complications or preterm birth (original source text reference noted as potentially misapplied) [1].
Recommendations – Bipolar Disorder in Pregnancy
- For women with long period without relapse, consider switching to safer drug (antipsychotic) or withdrawing treatment before conception (for at least first trimester) [1].
- For women with SMI, discuss referral to perinatal services for pre-conception advice [1].
- No mood stabiliser is clearly safe. NICE (UK) recommends mood-stabilising antipsychotics as preferable alternative [1].
- Women with severe illness or rapid relapse history should be advised to continue medication (except valproate), after risk discussion [1].
- NICE recommendations for lithium (see Lithium section above) [1].
- ACOG/COPE recommend detailed ultrasound/cardiac focus if taking lithium/anticonvulsants in first trimester [1].
- NICE, ACOG, COPE strongly advise against valproate use. Discontinue before pregnancy [1].
- UK: Valproate initiation/continuation restrictions (see Valproate section) [1].
- If valproate seen as only option (highly unlikely scenario), requires clear briefing of risks and written consent [1].
- NICE advises against carbamazepine for mental health if planning pregnancy/pregnant/breastfeeding. Discuss stopping [1]. If used, administer prophylactic vitamin K (mother/neonate) [1].
- ACOG recommends against discontinuing mood stabilisers (except valproate) due to relapse risk [1].
- NICE advises frequent lamotrigine level checks during pregnancy/postnatal period [1].
- Acute mania in pregnancy: Use antipsychotic; if ineffective, consider ECT [1].
- Bipolar depression in pregnancy: Use CBT (moderate); SSRI (severe). Lamotrigine is also an option [1].
Table 4: Mood Stabiliser Teratogenicity Rankings
| Medication Name | Specific Malformations & Neuro Risks | Absolute Malformation Risk | Risk Tier |
|---|---|---|---|
| Valproate | Neural tube defects, cardiac defects, motor/neurodevelopment delays, ASD [1] | ~10% [1] | |
| Carbamazepine | Neural tube defects [1] | Significant (lower than Valproate) [1] | |
| Topiramate | Orofacial clefts, small for gestational age [1] | High [1] | |
| Lithium | Ebstein's anomaly (cardiac), neonatal goitre, hypotonia [1] | Moderate / exists [1] | |
| Lamotrigine | Safer option; similar to baseline controls [1] | Low [1] |
A pregnant patient on a mood stabilizer requires blood level monitoring because clearance of the drug increases radically during pregnancy and drops sharply postpartum. Which medication is this?
Correct Answer (A): Under the Lamotrigine section, the text specifically states: "Clearance increases radically during pregnancy and reduces postpartum; frequent level monitoring necessary (NICE)." [1] Lithium requires monitoring too, but its clearance is related to GFR changes, whereas lamotrigine clearance changes are dramatically driven by glucuronidation induction [1].
Anxiety and Insomnia During Pregnancy and Postpartum High Yield
Anxiety disorders and insomnia are common in pregnancy. Preferred treatments are CBT and sleep-hygiene measures, respectively [1].
Sedatives
- First-trimester benzodiazepine exposure associated with specific malformations (e.g., oral clefts) in some studies, but others failed to confirm [1]. May be a marker for risk rather than causal [1].
- Benzodiazepine use associated with caesarean delivery, spontaneous abortion, NICU admission, ventilatory support, low birth weight, preterm delivery, small head circumference, small for gestational age [1].
- Third-trimester use commonly associated with neonatal difficulties (floppy baby syndrome) [1].
- A Taiwanese study (controlling for indication) found early pregnancy benzo/Z-drug use not associated with increased stillbirth/preterm birth, but increased risk of small for gestational age [1]. Late pregnancy exposure associated with substantially elevated risk of stillbirth and preterm birth [1].
Guidance on Benzodiazepines in Pregnancy
UK NICE: Advises not offering benzodiazepines except for short-term treatment of severe anxiety/agitation. Suggests gradual stopping if planning pregnancy, pregnant, or breastfeeding. ACOG: Recommends benzodiazepines be avoided or prescribed sparingly for perinatal anxiety [1].
- NICE (UK) advises not offering benzodiazepines except for short-term treatment of severe anxiety/agitation. Suggests stopping gradually if planning pregnancy/pregnant/breastfeeding [1].
- ACOG recommends avoiding or prescribing sparingly for perinatal anxiety [1].
- Promethazine appears not to be teratogenic (limited data) [1].
- Hypnotic benzodiazepine receptor agonists (Z drugs) probably not associated with increased congenital malformations, but increased risk of premature birth, low birth weight, small for gestational age reported [1]. Zolpidem may increase likelihood of caesarean section [1].
- Available data do not appear to show an association between in utero benzodiazepine/Z drug exposure and neurodevelopmental disorders [1].
Attention Deficit Hyperactivity Disorder (ADHD) in Pregnancy High Yield
- Methylphenidate and amfetamines are probably not major teratogens [1].
- A small increased risk of cardiac malformations reported with methylphenidate (not seen with amfetamines) [1].
- There may be a small increased risk of spontaneous abortion with methylphenidate and a small increased risk of premature birth and low birth weight with amfetamines [1].
MHRA Warning: Modafinil
The UK MHRA advises that modafinil should not be used during pregnancy due to potential increased risk of congenital malformations. Women of child-bearing potential must use effective contraception during treatment and for 2 months after stopping [1].
- In the UK, the MHRA advises that modafinil should not be used during pregnancy (risk of malformations) [1]. Effective contraception needed during use and for 2 months after stopping [1].
- Available data do not show an increased risk of neurodevelopmental disorders in children exposed to ADHD medications in utero [1].
According to the UK MHRA, which stimulant/wakefulness-promoting drug should NOT be used during pregnancy due to the risk of congenital malformations, requiring women of child-bearing potential to use effective contraception during and for 2 months after stopping?
Correct Answer (C): Under the MHRA Warning: "The UK MHRA advises that modafinil should not be used during pregnancy due to potential increased risk of congenital malformations. Women of child-bearing potential must use effective contraception during treatment and for 2 months after stopping." [1]
Breastfeeding High Yield
Breastfeeding
Content for the Breastfeeding section was not included in the provided text. This section would normally detail medication passage into breast milk, potential effects on the infant, and specific recommendations for different drug classes during lactation [1].