Antidepressants in Pregnancy D R S N E H A P A R G H I

Antidepressants in Pregnancy D R S N E H A P A R G H I

Overview Depression and its effects Antidepressants and their effects Birth defects Miscarriage Neonatal withdrawal Longterm consequences Breastfeeding considerations What to choose?

Depression Common problem A woman has a 10-25% risk of being diagnosed with a major depressive disorder in her lifetime 1 Greatest risk in childbearing years 14-23% of pregnant women with experience depressive episode At risk: low income, low education, poor social support, unplanned pregnancy, adolescents Pregnancy is a major physiological and psychological life event Stress of impending motherhood: particularly on background of poor social support, dysfunctional families, history of sexual abuse Biological changes: HPA overactivity and high circulating cortisol 1

Harmful effects of depression Maternal Risk of suicide most common indirect death (particularly postpartum) 3 Foetal Possible lower birth weight, increased risk of preterm birth Raised cortisol levels in offspring ---> increased vulnerability to psychopathology 2 Learning difficulties, behavioural problems 1 Increased risk of admission to NICU, lower APGAR scores 2 Breastfeeding Depressed mothers more likely to cease breast feeding

Discontinuation during pregnancy Discontinuation may lead to serious relapses Sample of 201 women showed that 43% experienced a relapse of major depression during pregnancy Exposure of a foetus to significant maternal depression may be as risky as exposure to antidepressants 2

Treatment options Behavioral therapy--first Line Support groups Counseling Psychotherapy Individual, group, family Pharmacotherapy TCAs SSRIs--used most often, most studied and less side effects Note: No psychiatric medication has been endorsed by the FDA for use during pregnancy The decision to place a pregnant patient on an SSRI is based on clinical judgment and the latest research

SSRIs Highest number of studies on their reproductive safety Most common Sertraline Fluoxetine Fluvoxamine Most SSRIs fit under the Category C on the pregnancy-risk factors Paroxetine Category D

TCAs Risk of overdose Lack of research on safety in pregnancy however few documented problems arising from use Pregnancy Category C

Risks First trimester Small increase in congenital defects; NOT statistically significant risk (RR 1.34 CI 1.00-1.79) and not supported by meta-analysis of comparative cohort studies therefore interpret with caution Paroxetine increased risk of cardiac abnormalities and possibly hypospadias Second trimester Small increased risk of preterm birth and lower birth weight Third trimester Neonatal withdrawal Persistent pulmonary hypertension of the newborn Possible intraventricular haemorrhage

Congenital malformations Hard to study, limited by small sample size Most studies have failed to demonstrate a link Studies demonstrating risk seem to have some bias Malm 2011 Finland retrospective cohort study 10 years of data Association between fluoxetine and paroxetine with ventricular septal defects and right ventricular outflow tract defects ACOG recommends Avoidance of use preconceptionally and during pregnancy if possible Consider foetal echocardiography if exposure in 1 st trimester

Neonatal withdrawal 10-30% risk 2 Symptoms: Hypotonia, irritability, excessive crying, sleeping difficulities, mild respiratory distress Self limiting, generally settle within 14 days Management: Admission to NICU/SCBU until resolution of Sxs Supportive care More likely to occur with paroxetine than other SSRIs

PPHN Failure of the normal circulatory transition that occurs after birth Asphyxia, tachypnoea, respiratory distress Right-to-left shunting PPHN results from increased pulmonary vascular resistance/delayed relaxation Serotonin: Vasoconstrictive properties Inhibits nitric oxide (vasodilator) Small increase in absolute risk from 1/1000 to 6-12/1000

Longterm effects Not well understood?behavioural problems?autism spectrum disorder

Breastfeeding SSRIs considered safe in breastfeeding Minimal infant dose in breast milk Sertraline and paroxetine have lowest infant dose Continuation may reduce the risk of postnatal depression

So what is a GP to do? Pre-conception counselling Explore the relative risks of depression compared to the risks of antidepressant use If symptoms have receded, consider a trial of slow cessation of medication Unplanned pregnancies May lead to alarm, anxiety and a sudden cessation of medication ---> 75% may develop a recurrence of depression before delivery Assessment of risks can reassure women that continuation is ok Relapse If relapse occurs during pregnancy, consideration of increased dose requirements Third trimester If concerns regarding neonatal withdrawal some doctors and patients may lower doses until after delivery Provide adequate psychosocial support

Which antidepressants Individualised approach High risk of relapse if ceasing or changing medication SSRIs preferred to TCAs or SNRIs Avoid paroxetine Sertraline seems to be antidepressant of choice Use minimum effective dose

References Williams A Antidepressants in pregnancy and breastfeeding 2007 Australian Prescriber; 30:125-7 O Keane V, Marsch M Depression during pregnancy 2007 BMJ; 334:1003-1005 http://www.blackdoginstitute.org.au/docs/safetyofantidepres santsinpregnancyandbreastfeeding.pdf Kieler H et al, Selective serotonin reuptake inhibitors during pregnancy and risk of persistent pulmonary hypertension in the newborn: population based cohort study from the five Nordic countries 2012 BMJ 2012;344:d8012 Abel D SSRIs in pregnancy 2013 Aug, Contemporary ObGyn RANZCP College Statement 2005 Guidance on the use of SSRIs and Venlafaxine (SNRI) in late pregnancy)