Psychiatric Management of Depression in Pregnancy and Post-Partum: Weighing the Risks

1
Psychiatric Management of Depression in Pregnancy
and Post-Partum Weighing the Risks

• Katherine C. Smith, D.O.
• Assistant Professor

2
Goals for Today

• Risk of untreated psychiatric illness in
  pregnancy
• Risk of medication use in pregnancy and lactation
• There is no such thing as ZERO risk
• How to effectively weigh the risks and benefits
  of treatment
• Resources

3
Live Births and Fertility Rates in U.S.

• Approximately 50 are unplanned pregnancies

• At least 500,000 pregnancies each year are
  associated with psychiatric illness

CDC Births Preliminary Data 2006 National
Vital Statistics Report. Volume 57, Number 7,
December 2007.
4
Unintended Pregnancies in the U.S.

• The proportion of unintended pregnancies was
  unchanged from 1994

• Risk Factors

Women ages 18-24 Low-income Cohabitation Minority
Finer, L and Henshaw K. Disparities in Rates of
Unintended Pregnancy in the United States, 1994
and 2001. Perspectives on Sexual and
Reproductive Health. Vol 38 (2), 90-96, 2006.
5
Myth Busters

• Pregnancy is a time of emotional well-being
• Category B is a safer category in pregnancy
• There is a specific algorithm for the treatment
  of pregnant patients
• It is best to stop psychotropic medications prior
  to conception
• It is best to taper psychotropic medications
  prior to delivery

6
MDD in pregnancy

• 10-16 of women have major depression during
  pregnancy
• Associated with problems for both mother and
  fetus
• When emerges in pregnancy, is frequently
  overlooked
• Pregnancy is neither protective, nor exacerbating
  for depressive disorders
• Under-recognized and under-treated in primary
  care settings

Cohen L, Nonacs R (editors) Mood and Anxiety
Disorders During Pregnancy and Postpartum (Review
of Psychiatry Series, Vol 24, Number 4).
Washington, DC, APPI, 2005
7
Antidepressant Use in Pregnancy

• Recent studies estimate up to 9 of pregnant
  women may take an SSRI during pregnancy
• Several studies have also shown an increase in
  antidepressant use
• SSRIs accounted for the largest increase

8
A Multisite Retrospective Study

• 118,935 deliveries 2001-2005, 6.6 women took
  antidepressants

• Antidepressant use increased from 2 deliveries
  in 1996 to 7.6 deliveries in 2005

• SSRI use increased from 1.5 in 1996 to 6.4 in
  2004

Andrade S et al. Use of antidepressant
medications during pregnancy a multisite study.
American Journal of Obstetrics and Gynecology.
Feb. 2008
9
Why is this important?

• All women of childbearing years are potentially
  pregnant until proven otherwise
• Approximately 50 pregnancies are unplanned
• 10-16 women have major depression during
  pregnancy
• Risk benefit analysis ideally prior to
  conception, every medication change!

10
Lauren

• 24 year old engaged Caucasian female with
  postpartum depression, polysubstance
  dependence-full remission, currently taking
  Venlafaxine and Bupropion
• 2 visits ago Can you refill my OCP?
• Last visit again addressed a risk benefit
  analysis
• Last week Im pregnant

11
Weighing the Risks and Benefits

• Risk of untreated mental illness
• Risk of relapse of psychiatric illness
• Effects of psychiatric illness on the fetus
• Teratogenicity of psychotropic medications
• Long term behavioral effects
• Incomplete reproductive safety data for
  medications

12
Risk of Untreated Psychiatric Illness in Pregnancy

• Maternal Depression may cause
• Preterm birth, low birth-weight, smaller head
• circumference, and lower Apgar scores
• Contribute to poor self-care, inattention to
  prenatal care
• Women are more likely to smoke, use alcohol or
  illicit drugs
• Children of depressed mothers are more likely to
  have behavioral problems, delays in cognitive,
  motor and emotional development
• Risk for suicide

Nonacs R, Viguera A, Cohen L. Psychiatric Aspects
of Pregnancy. Womens Mental Health, a
Comprehensive Textbook. Ed. Susan Kornstein and
Anita Clayton. New York, NY, 2002.
13
Anxiety and Stress in Pregnancy

• Lead to poor outcomes
• Increase cortisol and adrenocorticotropic hormone
  levels
• May be associated with preeclampsia
• May reduce uteroplacental blood-flow
• Antenatal anxiety predicts postpartum anxiety and
  depression

Cohen L, Nonacs R (editors) Mood and Anxiety
Disorders During Pregnancy and Postpartum (Review
of Psychiatry Series, Vol. 24, Number 4).
Washington, DC, APPI, 2005 Heron J, OConnor T et
al. The course of anxiety and depression through
pregnancy and the postpartum in a community
sample. J. Affect. Disord 8065-73,2004.
14
Depression Relapse in Pregnancy Cohen et al.
2006

• 43 of the women experienced relapse during
  pregnancy

• 26 who maintained medication relapsed

• 68 who discontinued medication relapsed

Cohen L, Altshuler L, Harlow B et al. Relapse of
Major Depression During Pregnancy in Women Who
Maintain or Discontinue Antidepressant Treatment.
JAMA Vol 295 (5), 499-507, 2006.
15
Risks Associated with Medications in Pregnancy

• Pregnancy loss or miscarriage
• Organ malformation or teratogenesis
• Neonatal toxicity or withdrawal syndromes
• Long-term neurobehavioral sequelae

16
Organogenesis
17
Weighing and Presenting the Evidence

• There is no such thing as ZERO risk
• There is no specific algorithm
• The goal is to minimize fetal medication
  exposure, and maximize mental health
• Even experts vary on interpretation of the
  current evidence!

18
SSRIs in Pregnancy

• No major teratogenic risk associated with SSRI
  use
• Possible increase in cardiac defects with first
  trimester exposure to paroxetine
• Adverse perinatal outcomes conflicting data
• Persistent pulmonary hypertension
• Possible increase in spontaneous abortion
• No significant developmental delay in children

Cohen L. Treatment of Bipolar Disorder During
Pregnancy. J. Clinical Psychiatry 68 (9), 2007
4-9.
19
Late 3rd trimester exposure

• Neonatal Behavioral Syndrome
• Symptoms include
• Jitteriness
• Tachypnea
• Tremulousness
• Hypertonia
• Restlessness
• Difficult to differentiate reported adverse
  outcomes related to
• Antidepressant exposure
• Antidepressant withdrawal
• Maternal depression and anxiety

20
SSRIs and Persistent Pulmonary Hypertension

• Cohort Study SSRIs in late pregnancy may be a
  risk factor for PPHN (Chambers et al 1996)
• Case-Control Study (Chambers et al 2006)
• 14 infants were exposed to an SSRI after the 20th
  week of gestation
• Retrospective design
• Absolute risk 7/1000 women
• Based on this study, in April 2006 the FDA
  required a label change to include SSRIs
  increasing the risk for PPHN

Chambers C, Hernandez-Diaz S, Van-Marter L et al.
Selective Serotonin-Reuptake Inhibitors and Risk
of Persistent Pulmonary Hypertension of the
Newborn. N Engl J Med. Vol 3546 579-587,
February 9, 2006.
21
Paxil and Cardiac Defects

• Multiple studies show no increased risk of
  cardiac defects with Paxil or other
  antidepressants
• Meta-analysis (Koren et al. 2007)
• Increased risk for cardiac malformation
• Women using antidepressants had higher numbers of
  echocardiograms, amniocentesis and ultrasounds
• Women on paroxetine used the drug for anxiety and
  panic
• Epidemiologic Study (Koren et al. 2008)
• 1,174 unpublished cases and 2,061 cases from
  published database studies
• The rate of cardiovascular defect falls within
  the normal rate in the general population

Bar-Oz, Einarson T, Koren G et al. Clinical
Therapeutics. 2007 29 918-926. Einarson A,
Pistelli A, Koren G. AJP. 1008 1-4. April, 2008
22
FDA Categories
?
23
Other Antidepressants

• Venlafaxine
• Trazodone
• Mirtazapine
• Duloxetine
• Bupropion
• MAOI inhibitors are avoided in pregnancy

24
Tricyclic Antidepressants

• No major risk for malformations
• Desipramine and nortriptyline preferred - less
  anticholinergic activity
• Perinatal syndromes described in infants
• Anticholinergic effects are transient (bowel
  obstruction, urinary retention)
• Withdrawal Syndrome
• No long-term neurobehavioral effects

25
Medication Reduction or Discontinuation Prior To
Delivery

• Adverse effects on the fetus
• Hypotonia
• Neonatal withdrawal syndromes
• Neonatal apnea
• Temperature dysregulation
• But rare, temporary, treatable, and reversible
• Higher risk of relapse in pregnancy and
  post-partum

26
Other Treatment Options

• Cognitive Behavioral Therapy
• Interpersonal Therapy
• Group Therapy
• Light Therapy

27
Electroconvulsive Therapy

• Safety well documented over 50 years
• Organ Dysgenesis
• Occasional reports of malformations but no direct
  causal link to ECT
• Intrauterine Growth Defects/Neonatal Toxicity
• None
• Neurobehavioral Teratogenicity
• Few case reports - developmental delays or MR
• No direct causal link to ECT
• Seizure threshold
• decreased by estrogen, and increased by
  progesterone

28
Lauren

• Given your risk factors, and the current
  evidence, I recommend
• I am still smoking, and Wellbutrin has decreased
  my cravings
• Explain her individual risks of being on both
  Effexor and Wellbutrin, and she chooses to
  continue with both at her current dosages

29
Recommendations for Antidepressant Treatment in
Pregnant Women

• Psychotherapy is first line for mild-moderate
  depression
• Psychotherapy antidepressant recommended for
  moderate to severe depression
• Individualized risk-benefit analysis
• No hx of antidepressant treatment SSRI
  antidepressant considered first-line
• Successful history of antidepressant treatment
  data should be reviewed with mom, and considered
  first line

Altshuler L, Cohen, L, Moline M et al. Treatment
of Depression in Women A Summary of the Expert
Consensus Guidelines. Journal of Psychiatric
Press 185-208, May, 2001.
30
Recommendations continued

• ECT for psychotic depression
• Review all risks and benefits of treatment
• Moms should be monitored carefully for increased
  depression, mania or psychosis
• Dosages may need to be adjusted
• Goal is monotherapy and minimal effective dosage

Altshuler L, Cohen, L, Moline M et al. Treatment
of Depression in Women A Summary of the Expert
Consensus Guidelines. Journal of Psychiatric
Press 185-208, May, 2001
31
Postpartum Depression versus Postpartum Blues
32
Risk Factors for Postpartum Depression

• Previous history of MDD- 24 risk
• Depression during pregnancy- 35
• Previous postpartum depression-50
• Stressful life events
• Marital dissatisfaction
• Demographic variables may be weak contributors
• Hormonal fluctuations

Burt, V. Hendrick, V. Clinical manual of Womens
Mental Health. Arlington, VA 2005.
33
Recommendations for Screening

• Edinburgh Postnatal Depression Scale
• PP Depression Scale
• Responsiveness of mom and baby
• Sleep patterns
• Weight loss or gain
• Assess for fears of infant harm

34
Treatment of Postpartum Depression in
Breastfeeding Women

• Mild to moderate depression first line is
  PSYCHOTHERAPY
• Moderate to severe depression antidepressant
  psychotherapy
• Clinical point
• No medication is FDA approved for breastfeeding
• No antidepressant has proven safer or more
  effective than another
• No specific algorithm for antidepressant choice

35
Antidepressants and Lactation

• American Academy of Pediatrics national
  immunization survey 2002
• More than two-thirds of breast-feeding mothers
  with depression are likely to start breastfeeding
• The risk benefit assessment for breast feeding
  women should include
• Known risk to the baby of untreated depression
• Efficacy of antidepressant medication for PPD
• Risk of exposure to baby

Pearlstein, Teri. Perinatal Depression Treatment
options and Dilemmas. Journal of Psychiatry and
Neurosciences 33(4)302-18, 2007.
36
Individualized Risk Benefit Analysis Plan
Risk of Untreated PPD
Benefits of Treatment
Previous Tx Of Depression
Risk of Antidepressant Treatment
Risk of Breastfeeding
Infant Serum Levels
Target Symptoms
Maternal Wishes
37
SSRIs and Lactation

• Paroxetine and Sertraline- 1st line
• Less than 10 maternal level
• Fluoxetine
• Exceeded 10 maternal level (22 cases)
• Citalopram
• Exceeded 10 maternal level (17 cases)
• Escitalopram and Fluvoxamine
• Few case reports

Academy of Breastfeeding Medicine Protocol
Committee Clinical Protocol 18 Use of
Antidepressants in Nursing Mothers. Breastfeeding
Medicine. VOl 3. (1), 2008.
38
Tricyclics, Heterocyclics, and Lactation

• Nortriptyline- undetectable in infant serum
• Growing evidence that other tricyclics appear to
  be safe
• Doxepin- cautioned due to hypotonia, poor feeding
• Mirtazapine- no adverse effects reported
• Bupropion
• SNRIs
• Trazodone- infant levels less than 10
• MAOI inhibitors- discontinue

Menon, S. Psychotropic Medication during
Pregnancy and Lactation. Arch. Gynecol. Obstet.
277 1-13, 2008.
39
Complementary and Alternative Medications for
Perinatal Depression

• Omega-3-fatty acids general data support use in
  pregnancy and postpartum
• S-adenosyl-methionine Some efficacy in reducing
  depression
• Folate some evidence to support augmentation for
  depression
• St. Johns Wort- some evidence of efficacy-
  possible drug interactions

Freeman, M. Complementary and Alternative
Medicine for Perinatal Depression. Journal of
Affective Disorders, 2008.
40
CAM continued

• Bright light therapy evidence supports potential
  use in perinatal and postpartum
• Acupuncture caution advised in pregnant women
• Massage some efficacy in pregnancy
• Exercise appears to have antidepressant effects

41
Recommendations for Antidepressant Treatment in
Lactating Women

• Individualized risk-benefit analysis
• Psychotherapy
• Mild to moderate depression
• Psychotherapy antidepressant
• Moderate to severe depression
• No prior antidepressant
• Paroxetine or Sertraline
• Prior successful antidepressant treatment
• Discuss data with mom consider as first line

Academy of Breastfeeding Medicine Protocol
Committee Clinical Protocol 18 Use of
Antidepressants in Nursing Mothers. Breastfeeding
Medicine. VOl 3. (1), 2008.
42
Recommendations Continued

• Review all risks and benefits of treatment
• Monitor carefully for increased depression,
  mania, or psychosis
• Evaluate infants prior to and after starting a
  new medication
• Strategies to decrease infant exposure not
  evidence-based

Altshuler L, Cohen, L, Moline M et al. Treatment
of Depression in Women A Summary of the Expert
Consensus Guidelines. Journal of Psychiatric
Press 185-208, May, 2001
43
Conclusions

• Every female patient of childbearing years is
  potentially pregnant!
• Ideally, decisions about psychotropic medications
  should be made prior to conception
• Consider non-pharmacologic strategies

44
Conclusions

• Risk-benefit analysis
• Minimize medications and poly-pharmacy-
  especially with AEDs
• Document, document, document!
• In all cases, optimizing the mothers health and
  ability to parent should be considered crucial
  for the developing child

45
Proposed Treatment Algorithm
Risk of Untreated Illness
Illness Severity
Risk of Relapse
Risk to Fetus
Goal is Sustained Healthy Mental State
Lowest Effective Dosage
Monotherapy
Consult!
46
Resources

• Mother Risk Program
• www.motherisk.org
• Massachusetts General Womens health
• www.womensmentalhealth.org
• United States National Library of Medicine
• http//toxnet.nlm.nih.gov

47
The Best New Resource in Town.
48

• Thanks for coming!!
• Questions?

49
References
ABM Clinical Protocol 18 Use of Antidepressants
in Nursing Mothers. Breastfeeding Medicine. VOl
3. (1), 2008.
Andrade S et al. Use of antidepressant
medications during pregnancy a multisite study.
American Journal of Obstetrics and Gynecology.
Feb. 2008
Altshuler et al. Pharmacological Management of
psychiatric illness in pregnancy dilemmas and
guidelines. Am J. Psychiatry 1996 153 592-606.
Bar-Oz B. Einarson T, Einarson A. et al.
Paroxetine and Congenital Malformations
Meta-Analysis and Considerations of Potential
Confounding Factors. Clinical Therapeutics, Vol
29(5)918-926, 2007.
Bupropion Pregnancy Registry Interim Report
September 1997 through 31 August 2007 Issued
December 2007 Glaxo Smith Kline
Burt, V. Hendrick, V. Clinical manual of Womens
Mental Health. Arlington, VA 2005.
CDC Births Preliminary Data 2006 National
Vital Statistics Report. Volume 57, Number 7,
December 2007.
Chambers C, Johnson K, Dick, L et al. Birth
Outcomes in Pregnant Women Taking Fluoxetine. N
Engl J Med 3351010-1015, 1996.
Chambers C, Hernandez-Diaz S, Van-Marter L et al.
Selective Serotonin-Reuptake Inhibitors and Risk
of Persistent Pulmonary Hypertension of the
Newborn. N Engl J Med. Vol 3546 579-587,
February 9, 2006.
Cohen L. Treatment of Bipolar Disorder During
Pregnancy. J. Clinical Psychiatry 68 (9), 2007
4-9.
Cohen L, Nonacs R (editors) Mood and Anxiety
Disorders During Pregnancy and Postpartum (Review
of Psychiatry Series, Vol 24, Number 4).
Washington, DC, APPI, 2005
Cohen L, Altshuler L, Harlow B et al. Relapse of
Major Depression During Pregnancy in Women Who
Maintain or Discontinue Antidepressant Treatment.
JAMA Vol 295 (5), 499-507, 2006.
Einarson A, Pistelli A, DeSantis M. et al.
Evaluation of the Risk of Congenital
cardiovascular Defects Associated with Use of
Paroxetine During Pregnancy. Am J Psychiatry in
advance- April 1, 2008.
Finer, L and Henshaw K. Disparities in Rates of
Unintended Pregnancy in the United States, 1994
and 2001. Perspectives on Sexual and
Reproductive Health. Vol 38 (2), 90-96, 2006.
50
Freeman M. Antenatal Depression Navigating the
Treatment Dilemmas. Am J Psychiatry Vol
164(8)1162-1165, 2007.
Gentile S. Prophylactic Treatment of Bipolar
Disorder in Pregnancy and Breastfeeding Focus on
Emerging Mood Stabilizers. Bipolar Disorders.
8207-220, 2006.
Heron J, OConnor T et al. The course of anxiety
and depression through pregnancy and the
postpartum in a community sample. J. Affect.
Disord 8065-73,2004.
Koren, G. Medication Safety in Pregnancy and
Breastfeeding. 2007
Menon, S. Psychotropic Medication during
Pregnancy and Lactation. Arch. Gynecol. Obstet.
277 1-13, 2008.
Newport D, Stowe Z et al. Psychiatric Disorders
in Pregnancy. Neurologic Clinics Vol 22 863-893,
2004.
Newport D, Viguera A, Nemeroff C et al. Atypical
Antipsychotic Administration During Late
Pregnancy Placental Passage and Obstetrical
Outcome. Am J Psychiatry, 1648, 1214-1220 August
2007.
Nonacs R, Viguera A, Cohen L. Psychiatric Aspects
of Pregnancy. Womens Mental Health, a
Comprehensive Textbook. Ed. Susan Kornstein and
Anita Clayton. New York, NY, 2002.
U.S. Food and Drug Administration. FDA Public
Health Advisory,Paroxetine. Available at
http//www.fda.gov/cer/drug/advisory/paroxetine200
512.htm. Accessed April 7, 2008
Viguera A, Stowe Z, Cohen C et al. Risk of
Recurrence in Women with Bipolar Disorder During
Pregnancy Prospective Study of Mood Stabilizer
Discontinuation. Am J Psychiatry. 16412
December 2007, 1817-1824.
Yaeger D., Smith H., Altshuler L. Atypical
Antipsychotics in the Treatment of Schizophrenia
During Pregnancy and the Postpartum. Am J
Psychiatry 16312, 2064-2070, 2006.
Yonkers K, Wisner K, Stowe Z et al. Management of
Bipolar Disorder During Pregnancy and the
Postpartum Period. Am J Psychiatry Vol 161
608-620, 2004.
51
Psychiatric Management of Depression in Pregnancy
and Post-Partum Weighing the Risks

• Katherine C. Smith, D.O.
• Assistant Professor

52
Other drugs and lactation

• Avoid in premature infants or hepatic immaturity
• Typical antipsychotics- safe in lactation
• Atypical antipsychotics- not recommended
• Mood stabilizers
• Lithium- up to the mother
• Tegretol- infant levels up to 60- no adverse
  events
• Depakote- up to 3- no adverse events
• Gabapentin- up to 100 maternal levels- not
  recommended
• Lamictal- infant levels range from 20-50- no
  adverse effects

53
Other drugs and lactation cont.

• Hypnotics and anxiolytics
• Temazepam and clonazepam- low milk-plasma ratios,
  undetectable in infants
• Buspirone, zaleplon, zopiclone- high
  concentrations in breast milk- contraindicated
• Zolpidem- compatible with lactation