ASSESSMENT AND TREATMENT OF PERINATAL MOOD DISORDERS'

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• ASSESSMENT AND TREATMENT OF PERINATAL MOOD
  DISORDERS.
• A/Professor Marie-Paule Austin
• University of NSW, Black Dog Institute,
• Royal Hospital for Women
• www.blackdoginstitute.org.au
• www.motherisk.org
• www.womensmentalhealth.org

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Perinatal mental health morbidity

• Child-bearing years peak onset of mood disorder
• 50 pregnancies unplanned
• Pregnancy
• not protective for mood disorders (recurrent/new)
• 10 depressive symptoms in pregnancy (13 p-p)

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Perinatal Maternal Morbidity
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• Prevalence Postnatal Depression 13
• prevalence of depressive symptoms is similar in
  late pregnancy10 (Fergusson 1996 Whiffen
  1992, Evans 2001)
• 30 postnatal depression begins in pregnancy
• Need to refocus from PND to Perinatal mood
• anxiety disorder

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Severe Mental Health Disorders in the Perinatal
Period

• 30 x risk of 1st psychotic episode 1st month p-p
• Women with severe illness have an 80 fold risk of
  suicide over other women in the 1st postnatal
  year
• Women with mood disorder who cease medication
  periconceptually, have a 90 risk relapse.

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Psychosocial Assessment in the Perinatal
Period
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Perinatal Mental Health Psychosocial
Assessment Definitions

• Perinatal Mental Health
• conception to 1st year postnatal
• Mother, infant, father/partner, family
• Psychosocial Assessment
• routine, universal review of maternal and infant
  emotional and social wellbeing.
• Includes broad identification of current/future
  risk of maternal depression, anxiety, psychosis,
  substance abuse, parenting and attachment and
  other relationship difficulties.

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Psychosocial Assessment

• Includes assessment of risk factors combined
  with a symptom measure (eg. NSW IPC model)
• Psychosocial Risk tool
• - Professional or self- administered (in presence
  of health care professional)
• - Assess the psychosocial context
• Used together with Edinburgh Depression Scale for
  current symptom self-harm evaluation
• Drug Alcohol Domestic Violence, risk to infant
  .

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Antenatal Risk Questionnaire
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Edinburgh Scale
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Psychosocial Assessment

• Universal Assessments at
• booking-in early pregnancy
• 1-3 months postpartum

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POST-NATAL DEPRESSION (PND)

• Incidence
• 3x higher rate of new onset depression within 5
  weeks of childbirth cf. matched control group
• greatest risk of depression than any other time
  in woman's life.
• often not diagnosed till much later

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• PND Psychosocial Risk Factors
• Period of great adjustment- complicated if
• History abuse emotional, physical, sexual
• Much ambivalence about pregnancy
• Anxious, low self-esteem, negative cognitions.
• Negative life events
• perinatal complications perceived as traumatic
• Unresolved TOP, miscarriage
• Poor social supports
• marital/family probs

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• PND Biological risk factors
• Hormonal factors significant for a small
  subgroup
• Past history of PND, or depressive disorder
• 2-4 x risk of subsequent PND
• family history affective illness

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• POST-NATAL DEPRESSION
• Detection
• no different to other depressions but need to
  differentiate from adjustment to childbirth
• 50 depression undetected by GP's ECN's
• Detection can be confounded by
• a) "unsettled" baby
• b) disturbed sleep/anxiety seen as normal in this
  context
• c) tendency to downplay symptoms as "normal"
• d) focus on physical aspects of p-p

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• POST-NATAL DEPRESSION
• Symptoms
• loss of pleasure
• mood depressed, irritable, anxious,
  labile
• sleep reduced (independent of baby)
• social withdrawal
• Panic attacks/agoraphobia

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• POST-NATAL DEPRESSION
• Symptoms (cont)
• poor "bonding"emotionally detached
• marital problems
• "unworthy" mother baby better off without
  me
• undue concern for baby's health
• obsessions contamination/babys weight
  gain
• suicidal/infanticidal ideation

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• POST-PARTUM PSYCHOSIS
• Incidence 1-2/1,000
• Onset 75 within 2-3 weeks
• Diagnostically not a single entity
• 75 affective most bipolar
• 25 szia
• organic
• Risk Factors primiparity, past hx.

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• POST-PARTUM PSYCHOSIS
• Clinical features (Affective type)
• rapid onset
• depressed or manic (mixed)
• perplexity and confusion
• mood-congruent psychotic features

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• POST-PARTUM PSYCHOSIS
• Outcome
• complete recovery for index episode
• subsequent puerperal psychosis
• 50-100 ( nb. within 2 yrs)
• lifetime recurrence depression 60-80
• bipolar/szia (80)

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Main assessment issues 1) establish rapport and
trust 2) adjustment to parenthood vs.
depression/anxiety disorder 3) dangerousness
(self/child) 4) adequate supports ? 5) evaluate
mother-infant parental rel/ship 6) exclude
organic pathology hypothyroidism, anemia 7)
combined psychol/pharmacol approach 8)
mothercraft/ parenting skills
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MEDICATION
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Fetal adverse Outcomes with Drug Exposure in
Pregnancy

• i) Structural teratogenicity
• 1st T birth defects
• (base rate 2-2.5)
• ii) Perinatal complications
• 3rd T poor obstetric or neonatal outcome
  withdrawal/toxicity 1st week p-p
• iii) Neurobehavioural sequelae
• Developmental delays, learning difficulties with
  exposure at any time

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Passage of antidepressants across placental
barrier

• Umbilical cord blood levels
• SSRIs In utero exposure between 20-100
  (Hendrick 2003, Rampono 04)
• TCAs 60-80 more for metabolites (Loughhead
  2006)

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SSRI Antidepressants
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Antidepressants In Utero Prospective,
Controlled Cohort Studies
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Antidepressants and miscarriage

• A recent meta-analysis examined rates of
  miscarriage in 1,534 women exposed to
  antidepressants in early pregnancy vs. 2,033 non
  exposed (Hemels 2005).
• Slight increase in miscarriage (12.4 vs 8.7)

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SSRIs and birth defects 2008

• Einarson (May 2008 AJP)
• Examined aggregated data across 12 studies on
  3,235 infants exposed to Paroxetine in 1st
  trimester.
• Cardiac defects in exposed and unexposed samples
  were both 1.2 ie. within normal range ( 1
  cardiac defects in normal population).
• Conclusion
• Aropax NOT associated with increased cardiac
  defects
• SSRIs not associated with birth defects.

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Late pregnancy SSRIs persistent neonatal
pulmonary hypertension (PPHN)

• Generally
• PPHN 3-5 infant mortality sigt morbidity in
  another 50.
• Chambers 2006 study suggested an association with
  increased risk for PPHN in newborns exposed to
  antidepressants in utero after 20 weeks.
• None of the babies in the antidepressant group
  died
• Absolute risk if true finding is 1 of exposed
  infants
• Significant methodological issues.
• Chambers et al. (2006). New England Journal of
  Medicine

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SSRI Neonatal withdrawal symptoms

• Nervous system, motor incl. brief seizures.
• Respiratory (not seen in opiate withdrawal
  syndromes)
• Gastrointestinal
• Onset within 1-2 days post-partum
• Usually last 2-3 days

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Management late pregnancy SSRI exposure

• FDA Canadian agencies recommend slowly reduce
  cease SSRI late pregnancy
• Not based on sound evidence
• Adverse effect of keeping mother unmedicated
• 2006 ANZ College Psychiatrists guidelines
• (ranzcp.org.au) suggest remain on SSRI if
  required

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Neurobehavioural Sequelae Antidepressant
prospective studies
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Mood Stabilisers
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Anticonvulsants Pregnancy

• 5 Anticonvulsant Registers worldwide
• Valproate
• risk congenital malformations 15
• 7 -10x increase in neural tube defects with
  first-trimester exposure
• ? dose dependent ? risk gt 1,000 mg/day (Morrow
  2005) .
• Lamotrigine
• Prospective study Lamotrigine not associated
  with increased risk birth defects overall
  (Cunnington 2005) but may be increased cleft
  palate at dose gt 200mg

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Valproate Neurobehavioural outcomes

• Retrospective study of epileptic mothers (N 249)
  identified reduced verbal IQ in school-aged
  children (6-16yo) exposed to Valproate vs.
  non-exposure (Vinten 2005)
• Increased rates of autism Asbergers.

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Risks of Lithium in Pregnancy

• Ratio of lithium in umbilical cord blood to
  maternal blood is 1.05 across a range of
  maternal concentrations.
• Infant exposure thus very significant
• 1st T 10-20 increased rates of Ebsteins
  anomaly (1 1,000)
• Late 3rd T Floppy baby syndrome
• Long term outcome 5 year prospective F/U 80
  infants no developmental delays cf. controls

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Lithium use in pregnancyNewport et al 2005

• frequent levels
• thyroid function tests pre postnatal
• Cease lithium as go into delivery
• Ensure adequate hydration
• immediate recommencement lithium p-p if ceased in
  pregnancy at prepregnancy dose
• Ensure adequate sleep post-partum to reduce risk
  relapse

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Antipsychotics
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Antipsychotics in pregnancy

• 1st Trimester
• Olanzapine control prospective case studies (Ns
  96, 60) (Ernst Goldberg 2002, McKenna 2005)
  Quetiapene (n 36), Risperidone (n 50) no
  increase in congenital anomalies comparable
  birth weights, gestation (McKenna 2005)
• Haloperidol control prospective study N 188
• ? premi labour no major teratogenic risk (?
  need U/S to exclude limb defect) (Diav-Citrin
  2005)

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Antipsychotics in pregnancy

• Schizophrenic women on atypical antipsychotics,
  have higher rates of infants with neural tube
  defect because of obesity and low folate levels
  (Koren 2002)
• Restlessness, tremor, jaundice bowel
  obstruction p-p with older antipsychotics

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BREASTFEEDING

• lt10 levels in breastmilk considered safe.
• SSRIS lt 5 levels in breastmilk
• Efexor 7 level
• Valproate very low levels
• Lithium up to 50 maternal levels
• Olanzapine Risperidone levels lt 5

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Early postpartum prophylaxis

• Lithium
• 3 small retrospective case control bipolar
  studies
• 3-5 fold rates of relapse in those not commenced
  on prophylactic lithium immediately p-p
• Olanzapine
• ? Role in relapse prevention if given immediately
  p-p
• Antidepressants
• Wisner 2001 Nortryptiline not useful
• Wisner 2004 SSRI useful

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General Considerations in Pregnancy

• Collaborative decision discuss risk-benefit
  ratio with mother father
• Attempt drug-free pregnancy.
• anticonvulsants ultrasound at 16-18 weeks
• 5mg folate preconception
• Always use minimum effective doses.
• Observe infant for toxicity/ withdrawal 3 days p-p

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Specific Considerations in Pregnancy

• 1 Antidepressants
• SSRIs, TCAs, Efexor safe 1st T
• ?? avoid Aropax/Efexor late exposure
• Monitor infant 3 days p-p
• 2 Antipsychotics
• Newer antipsychotics relatively safedepot no
  data
• 3 Mood stabilisers
• If possible avoid 1st T epsecially Valproate
• Ultrasound echo at 16-20 weeks
• Treat mania with antipsychotic 1st T

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Conclusions

• Causal links between maternal mental illness,
  exposure to psychotropes adverse outcome for
  offspring need further elucidation
• Must balance potential adverse effects of
  medication versus those of illness per se upon
  the infant and negative impact of untreated
  illness upon mother
• Risk benefit assessment for each case

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TAKE HOME MESSAGES

• Significant psychological morbidity and mortality
  in perinatal period
• May impact adversely on infant outcomes
• Routine, universal brief psychosocial assessment
  critical for holistic perinatal care
• Psychotrope use in pregnancy risk-benefit
  analysis for infant and mother

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Bipolar case vignette 1

• JG is a 36 yo. married mother of 2
• Severe recurrent psychotic manic depressive
  episodes since 18yo. Best when on Li Olanzapine
• JG was on Lithium 1,000mg with both pregnancies
• - 1st child was born with VSD
• - 2nd child born with Epsteins anomaly Wolf
  Parkinson White syndrome requiring Digoxin
  Sotolol.

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Bipolar case vignette 1

• JG developed gestational diabetes during 2nd
  pregnancy while on Olanzapine 10mg ( Li)
• Couple concerned about how to proceed with 3rd
  pregnancy
• What would be your Management?

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Vignette 2

• KM
• 38 year old, married, corporate lending manager
• First manic episode 4 months p-p
• Involuntary admission - 3 weeks inpatient
• Psychotic features on admission
• Olanzapine 20mg, Clonazepam and Lithium 900mg
• Reluctantly persevered with Lithium 625mg levels
  .5 - .6mmol/l
• Took a year before fully recovered - significant
  concentration problems

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Vignette 2

• KM (cont)
• Essentially demoted at work due to slow recovery
  phase
• Marital relationship very strained as husband
  wary of relapse and traumatised by her mental
  state at height of episode
• After 12 months, keen to cease Lithium and try to
  conceive second baby - time running out
• Husband very anxious about wife coming off
  medication
• What would you advise?

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Mothersafe

• Statewide phone in counselling for health workers
  women with concerns re use of medication in
  pregnancy breastfeeding
• Based at RHW
• Telephone numbers
• 93826539 (Sydney metropolitan callers)
• 1-800 647848 (non-metropolitan NSW )

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ADEC CLASSIFICATION OF PSYCHOTROPIC DRUG USE IN
PREGNANCY ANTIDEPRESSANTS BENZODIAZEPINES 1.
Tricyclic Antidepressants All (except
clonazepam) C All C Clonazepam D
2. SSRIS MOOD STABILISERS
Fluoxetine B2 Carbamazepine D
Fluvoxamine B2 Sodium Valproate D
Paroxetine B3 Lithium D
Sertraline B3 Citalopram
B3 ANTIPSYCHOTICS 1. Typical 3.
Other All C Mianserin B2 2.
Atypical Moclobemide B3
Clozapine C Nefazodone B3
Olanzapine B3 Phenelzine B3
Pimozide B1 Tranylcypromine B2
Risperidone B3 Venlafaxine
B2 Zuclopenthixol C Australian Drug
Evaluation 1996.