Antidepressants in Pregnancy - DR SNEHA PARGHI

Antidepressants in Pregnancy

        DR SNEHA PARGHI

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 lifetime1
    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 cortisol1

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 psychopathology2
   Learning difficulties, behavioural problems1
   Increased risk of admission to NICU, lower APGAR scores2

 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
  antidepressants2

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 1st trimester

Neonatal withdrawal

 10-30% risk2
 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)