Psychiatric Medicines During Pregnancy

Psychiatric medicines in pregnancy treat illness that carries its own risk: untreated depression, bipolar disorder and psychosis raise rates of preterm birth, low birth weight, self-harm, suicide, infanticide risk and postpartum relapse. Relapse after stopping is common (about 70% for antidepressants in recurrent depression, and over 50% for lithium in bipolar disorder within months).

Principle. Continue an effective medicine with a reasonable safety record rather than switch to an unfamiliar one; use the lowest effective dose; avoid polypharmacy; combine with psychological therapy.

Perinatal period. Postpartum psychosis (about 1 to 2 in 1000 births, higher in bipolar disorder) is an emergency starting within days to 2 weeks of birth.

Depression and anxiety.

• Sertraline 50 mg orally once daily, increased by 25 to 50 mg at 1 to 2 week intervals to 200 mg daily.
• Escitalopram or citalopram 10 to 20 mg daily (citalopram maximum 40 mg daily, 20 mg over age 60).
• Fluoxetine 20 to 60 mg daily (long half-life; neonatal adaptation less marked but infant exposure in breast milk higher).
• Venlafaxine modified release 75 to 225 mg daily (monitor blood pressure); mirtazapine 15 to 45 mg at night; nortriptyline 25 to 100 mg and amitriptyline 25 to 150 mg at night.
• Avoid starting paroxetine (cardiac malformations, small excess).

Bipolar disorder.

• Lithium: first trimester use is a risk-benefit decision (small rise in cardiac defects, absolute risk under 1 to 2%). If continued, give in 2 to 3 divided doses, trough level 0.4 to 0.8 mmol/L, check monthly to 34 weeks, then weekly.
• Quetiapine 300 to 800 mg daily; olanzapine 5 to 20 mg daily; haloperidol 1 to 10 mg daily; lamotrigine 100 to 400 mg daily for depressive prevention (titrate 25 mg for 2 weeks, 50 mg for 2 weeks, then increase by 50 mg weekly).
• Avoid valproate and carbamazepine.

Psychosis. Continue the established antipsychotic: olanzapine, quetiapine, risperidone 2 to 6 mg daily, aripiprazole 10 to 30 mg daily, haloperidol. Clozapine 200 to 450 mg daily may continue if it is the only effective drug (maximum 900 mg daily); monitor neutrophils, constipation and glucose.

Acute agitation. Lorazepam 0.5 to 2 mg orally or IM, or haloperidol 2.5 to 5 mg IM with promethazine 25 to 50 mg IM, short courses. Electroconvulsive therapy is effective and safe in all trimesters for severe depression, mania, catatonia and psychosis with foetal monitoring.

Anxiety and insomnia. Psychological therapy first; short-term lorazepam, diazepam or hydroxyzine only if needed. Avoid benzodiazepines in the weeks before birth where possible.

Postpartum restart. Restart lithium on the day of birth at the pre-pregnancy dose with a level within 5 to 7 days and encourage sleep protection; prophylactic antipsychotic or lithium started within days of birth in women with prior postpartum psychosis or bipolar disorder.

Foetal and neonatal effects. SSRIs and SNRIs late in pregnancy: poor neonatal adaptation in about 30% (jitteriness, feeding problems, respiratory distress, hypoglycaemia) lasting days; persistent pulmonary hypertension of the newborn (about 3 to 4 in 1000 versus 1 to 2 in 1000, small absolute risk). Do not stop the drug near term to avoid this; tell the neonatal team. Lithium near term: neonatal hypotonia, thyroid effects and diabetes insipidus.

Metabolic. Olanzapine, quetiapine and clozapine raise gestational diabetes and weight gain; screen early for glucose.

Serious reactions. Serotonin syndrome with combined serotonergic drugs (SSRIs with tramadol, linezolid, triptans, ondansetron at high dose); neuroleptic malignant syndrome; lithium toxicity (tremor, ataxia, vomiting, confusion; level over 1.5 mmol/L) precipitated by dehydration, hyperemesis, NSAIDs, ACE inhibitors and thiazides.

Interactions. Fluoxetine and paroxetine inhibit CYP2D6 (raising metoprolol, risperidone, tricyclics); carbamazepine and rifampicin lower clozapine, quetiapine and sertraline levels; smoking cessation raises clozapine and olanzapine levels by 50% or more.

Special groups.

• Kidney impairment: lithium clearance rises in pregnancy and falls after birth; frequent levels.
• Liver impairment: reduce antipsychotics and avoid duloxetine.
• Breastfeeding: sertraline and paroxetine give the lowest infant levels; lithium needs infant monitoring (thyroid, renal, level); avoid clozapine unless the infant is monitored; olanzapine and quetiapine acceptable.
• Regional: substance use (khat, alcohol, cannabis) is frequent and worsens mood and psychosis; khat has amphetamine-like effects and also interacts with antihypertensives; screen at every visit.

Monitoring. Mood and suicide risk each visit using a structured scale. Lithium levels every 4 weeks to 34 weeks then weekly, with creatinine, calcium and TSH each trimester. Weight, fasting glucose, lipids and blood pressure on antipsychotics. Clozapine neutrophil counts on the usual weekly then monthly schedule. Detailed anomaly scan and foetal echocardiography after first trimester lithium.

Stopping rules. Do not stop abruptly. Taper antidepressants over 4 or more weeks only if remission has been sustained and relapse risk is low. Hold lithium during hyperemesis, dehydration or labour onset and restart after birth.

Referral and escalation. Refer to perinatal psychiatry for bipolar disorder, psychosis, clozapine or lithium use, and previous postpartum psychosis. Any suicidal intent, psychotic symptoms or infant harm thoughts need same-day specialist assessment and admission to a mother and baby unit where available.