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Perinatal Depression: The Most Common Complication of Childbirth

Perinatal Depression: The Most Common Complication of Childbirth . Katherine L. Wisner, M.D., M.S. Director, Women’s Behavioral HealthCARE Professor of Psychiatry, Obstetrics and Reproductive Sciences, Epidemiology, Women’s Studies Assoc. Investigator, Magee Women’s Research Inst.

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Perinatal Depression: The Most Common Complication of Childbirth

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  1. Perinatal Depression: The Most Common Complication of Childbirth Katherine L. Wisner, M.D., M.S. Director, Women’s Behavioral HealthCARE Professor of Psychiatry, Obstetrics and Reproductive Sciences, Epidemiology, Women’s Studies Assoc. Investigator, Magee Women’s Research Inst. Adjunct Faculty, RAND Corporation, Pittsburgh Western Psychiatric Inst. And Clinic/Univ. Pittsburgh www.womensbehavioralhealth.org; www.MedEdPPD.org

  2. Disclosures • Pfizer: Ziprasidone Pharmacokinetics during Pregnancy-closed by KLW • GSK: Speaker’s Bureau • Donation of placebo patches from Novogyne Pharmaceuticals, a joint venture between Novartis Pharmaceuticals Corporation and Noven Pharmaceuticals, Inc., for an RCT of estradiol patch vs. sertraline vs placebo for PPD

  3. Session 1

  4. Perinatal Depression

  5. Maternal Depression • You say that I’m depressed • I wonder if you understand • You’ve never lived, I think • In this God-forsaken land • I always fight to function • I’m fighting to survive • I’m trying desperately to remember • What it’s like to feel alive • You say I’m carrying life inside • How can that really be? • How could life possibly survive • In a non-existent me?

  6. Major Depression • Over the last two weeks, most of the day nearly every day, five of the following (one symptom must be mood or interest): • Depressed mood • Diminished interest/pleasure • Weight loss/gain unrelated to dieting • Insomnia/hypersomnia • Psychomotor agitation/retardation • Fatigue or loss of energy • Feelings of worthlessness/guilt • Diminished ability to concentrate • Recurrent thoughts of death

  7. Postpartum Depression is NotThe Baby Blues • Not a clinical disorder - 50% to 80% of new mothers, not usually seen by physicians • Anxiety, mood lability, crying spells • Transient, no pervasive mood disturbance • Gone by day 10 postpartum! • Differentiate from depression by transience and low-level symptoms; be more suspicious if she has a history of depression

  8. Postpartum Psychosis is not just really bad depression • Onset in first few weeks post-birth; delusions/hallucinations are bizarre, cognitive difficulties prominent • Bipolar disorder! Mania or psychotic depression; use ECT, mood stabilizers • Differentiate from obsessional thoughts • Very high risk for recurrence after later births; prevention for patients who have bipolar disorder is good management

  9. Madness or Malice? Vermin or Victim?

  10. Andrea Yates • Devoted mother of five, nurse, home-schooling; two suicide attempts in 1999 • She did not hide the crime. “My children were not righteous. They were doomed to perish in the fires of Hell.” • She was Satan, he would be executed when she was executed, 666 on scalp • Agreement: severe mental disease, she knew killing was legally wrong, and she thought the killing was in the best interest of her children (“altruistic homicide”) • Two weeks before the killings, her antipsychotic drug was discontinued

  11. Epidemiology of Postpartum Episodes

  12. Etiology: Is it my hormones?(Bloch, Am J Psych 2000;157:924-930) • Induced hypogonadism, added supraphysiologic doses of estradiol and progesterone for 8 weeks; withdrew steroids double-blind model • 5/8 women with history of PPD developed symptoms, 0/8 women with no history • Hormones interact with variable(s) to risk of depression; but 25% of women who have had PPD develop it after subsequent births (not all!) • Liability to depression: stressful life events, genetic factors, prior history of major depression, neuroticism (Kendler, Am J Psych 1993;150:1139-1148

  13. Depression and its Concomitants Affect Multiple Domains of Perinatal Health • Symptoms of Depression=physiological dysregulation • Appetite Effects Underweight, Overweight, Nutrition • Cognitive changes; attention to self and infant safety • Prenatal/ postnatal care compliance • Use of other drugs/smoking

  14. Depression and its Concomitants Affect Multiple Domains of Perinatal Health • Choice of feeding methods for infant • Psychosocial relationships are crucial for support after birth • Marital discord • Interactional partner for infant • Use of health services for infant • Loss of employment/ Health insurance

  15. Treatment of Perinatal Depression

  16. Treatment Principles • Complex genetics-environmental interaction etiology creates multiple types of intervention • Treat until well, not just “better” • If a single episode, treat for six months after achieving wellness, longer for 2 episodes; consider maintenance for 3 or more episodes • Patient choice, treatment availability and resources are primary considerations

  17. Remission Recovery Relapse Recurrence Normal mood + Relapse Symptoms Response Severity 50% improvement + Progression to disorder Depression Continuation Maintenance Acute Clinical Stages in the Treatment of MDD Time Adapted from Kupfer DJ. J Clin Psychiatry. 1991;52(Suppl):28-34.

  18. Pregnancy

  19. Psychotherapy • Spinelli MG: Interpersonal Psychotherapy for depressed antepartum women: a pilot study.Am J Psych 154:1028-1030, 1997 • IPT, an effective form of treatment for depression, efficacy data for use during pregnancy • Targets interpersonal distress and effect on mood

  20. Interpersonal Psychotherapy • 16-week RCT of IPT vs. parenting education control program (PEP) • 50 enrolled; 38 completers • IPT > PEP on Outcomes: Edinburgh Postnatal Depression Scale (self-report), the Hamilton Depression Rating Scale, and Clinical Global Impressions • IPT should be a first-line treatment in the hierarchy of treatment for antepartum depression

  21. 22 PEP IPT-P 20 18 16 14 12 10 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 IPT-P vs. PEP in Depressed Pregnant Women: EPDS scores (p=.005) EPDS IPT-P Phase

  22. Supportive Psychotherapy Freeman et al. Omega-3 fatty acids and supportive psychotherapy for perinatal depression: a randomized placebo-controlled study. J Affective Disord 110:142-8, 2008

  23. New Environmental Approaches • Aerobic Exercise (> 30 minutes of moderate intensity physical exercise, 3 to 5 days per week) Dunn et al, Am J Prev SRI 2005;28:1-8, 2005 • Nutritional status; Pregnancy and lactation as a nutritional challenge.Bodnar and Wisner. Biol Psych 58:679-685, 2005.

  24. Bright Morning Light Therapy • Bright Morning Light Therapy, 10,000 lux commercial UV blocked box; pregnancy-- Epperson et al. J Clin Psych 65:421-425, 2004; Oren DA et al. Am J Psych 159:666-669, 2002. Golden et al:APA review and meta-analysis- Am J Psych 162:656-662, 2005 • Data support efficacy in non-seasonal depression: a non-pharmacologic somatic RX for depression

  25. Bright AM Light Treatment PregnancyOren et al. Am J Psych 159:666-669, 2002.

  26. Toon

  27. Risk-Benefit Decision-Making for Depression during Pregnancy: A Framework • Wisner et al: Risk-benefit decision-making for treatment of depression during pregnancy. Am J Psych 157: 1933, 2000 • Healthy outcomes for mother and baby are the rule rather than the exception!

  28. Depression Recurrence during Pregnancy • Recurrence risk for women who either maintained or discontinued antidepressants proximal to conception (Cohen et al- JAMA. 2006;295:499-507) • Significantly more women who discontinued (44/65, 68%) compared to women who maintained (21/82, 26%) antidepressant treatment suffered recurrent MDD. • Most recurrences emerged rapidly (50% in the first trimester, and 90% by the end of second trimester).

  29. Reproductive Outcome Domains Framework • Intrauterine fetal death • Major birth defects (approx 3% in the general population) • Growth Effects • Behavioral Teratogenicity • Neonatal Syndrome Respiratory Distress Persistent Pulmonary Hypertension of the Newborn These domains are impacted by both psychiatric disorders and antidepressants

  30. SSRI -Outcome Domains • Intrauterine fetal death -No evidence • Major birth defects – Specific defects (if any) are rare and absolute risks are small.Greene, M. F. (2007). Teratogenicity of SSRIs -- Serious Concern or Much Ado about Little? NEJM 356: 2732-2733

  31. Growth Effects: SSRI use, gestational weight gain and neonatal low birth weight • Chambers et al. , NEJM 1996 • 100 exposed early; 73 late (most through pregnancy) • ~ 3 X rate of preterm birth for FLX-exposed (14.3% late, 4.1% early, 5.9%, control) • For full term infants, birth weights, p=.04 3589 + 500 g (early) 3392 + 500 g (late) 3556 + 50 g (control) • Mean (SD) total maternal weight gain, p=0.01 Exposed early: 37.4 (15.4) lb. Exposed late: 30.8 (15.4) lb.

  32. Analysis of gestational weight gain Cumulative weight (g) Weeks of gestation Pregnancy ‘costs’ ~85,000 kcal Modified from Hytten, 1991

  33. Institute of Medicine weight gain recommendations (1990) *for singleton gestations; BMI, body mass index (weight (kg) / height (m)2)

  34. Antidepressant Use during Pregnancy (ADUP) Study

  35. ADUP: Pre-Pregnancy BMI and Weight Gain Weight Gain not signif. different across groups; pre-conception BMI higher in depressed women

  36. ADUP: Birth Weight

  37. Preterm Birth and SSRI: Depression or Drug Treatment? • Maternal SRI treatment associated with preterm birth across multiple studies • Oberlander et al (Arch Gen Psych 63:898-906, 2006) studied SRI-exposed infants vs. DE exposed: SRI > DE on birth weight, gestational age, proportion born at <37 weeks, neonatal respiratory distress, jaundice and feeding problems • For propensity score matched DE exposed vs. SRI exposed neonates, ONLY BW below 10th percentile and respiratory distress remained • Depression and SRI affect similar outcomes

  38. Preterm Birth and SSRI: Depression or Drug Treatment? • Prospective observational design, Suri et al (2007)studied 90 women • 49 MDD treated with antidepressants during pregnancy • 22 had MDD- not treated or limited exposure • 19 had neither exposure • Rates of preterm birth (14.3%, 0%, 5.3%, respectively- again, ~ 3 X greater for drug exposed • Depression during pregnancy did not affect outcome measures • SRI treatment was associated increased risk for preterm birth

  39. ADUP Preterm Birth Rates Preterm Birth Rates are higher in both SSRI throughout and MDD throughout

  40. Neonatal Syndrome • Poor neonatal adaptation in 31.5% of infants in late-exposed group, 8.9% in early-exposure group for fluoxetine (Chambers et al, NEJM 335:1010-1015, 1996 • Acute effects or withdrawal possible from any antidepressant; typically these are transient-about 2 weeks (Moses-Kolko et al, JAMA 293:2372-2382, 2005) • Restlessness, rigidity, tremor • Transient, usually less than two weeks • No long term developmental sequelae

  41. Specific Signs Reported to FDA AERS by Frequency of Occurrence (N=57 Infants) Yellow= CNS Signs Red = Neuro/muscular signs Blue= GI / Respiratory/ Autonomic signs

  42. Do all SSRIs predispose to neonatal complications? • Paroxetine • Most common drug in the case literature • High variability in onset time (birth–5 days postpartum) • Anticholinergic→ cholinergic overdrive • Fluoxetine • 4-fold increase in relative to unexposed newborn • Increased likelihood of respiratory disturbance • Develops by 4 hours of life [half-life (7 days)] • Sertraline, citalopram, escitalopram, fluvoxamine • Make inferences based on pharmacology

  43. Management: Toxicity • Taper maternal drug 10 days- 2 weeks prior to EDC • if risk of maternal illness doesn’t outweigh risk of complications • Mild symptoms: Conservative management strategies • Frequent small feeds /high calorie if needed • “Five S” of infant calming (Karp): Swaddling, Shhh, Soft Shaking, Sucking, Swinging • Maternal skin to infant skin contact • Severe symptoms • What about drug management?

  44. Persistent Pulmonary Hypertension of the Newborn • Chambers et al(NEJM 354:579-587, 2006) - increased risk of PPHN with SSRI treatment after 20 weeks gestation. • Odds of PPHN from late pregnancy compared to early or no exposure was 6.1 (95% CI=2.2 -16.8). • No increased risk of PPHN for nonserotonergic drug exposure • No infant deaths is in this study • Absolute risk = 6 -12/ 1000 births (0.6 to 1.2%); 14 SSRI exposed vs. 6 controls exposed.

  45. From - http://www.health.uab.edu/14535/

  46. ADUP: Neonatal Syndrome • Outcomes: NICU admissions, 10 signs from PES, incl. respiratory signs • NICU admissions not significantly different after adjustment for gestational age • Neonatal signs did not differ across groups except for less favorable 5 minute Apgar scores in continuous SRI exposed compared to nonexposed infants. • In our sample, there were low proportions of women exposed to high risk drugs -only 2 women were treated with paroxetine (5%) and 10 with fluoxetine (25%).

  47. Take Home Points • Intrauterine Fetal Death-No evidence; women with SRI and/or depression exposure have a higher risk for miscarriage • Physical Malformations-Specific defects (if any) are rare and absolute risks are small. • Growth- Maternal Weight Gain, pregnancy duration, infant birth weight- No significant differences in weight gain due to SRI. SGA inconsistently reported. Preterm birth is a converging finding for SRI exposed neonates but ; however, depression is associated with the same level of risk for preterm birth.

  48. Take Home Points • Behavioral Teratogenicity-No differences in cognitive function, verbal comprehension, expressive language, mood, arousability, activity levels, distractibility, behavior problems, temperament (TCA, FLX); Casper et al (2003) reported less favorable motor (not mental) development in SSRI exposed vs. control in toddlers. • Neonatal Syndrome-Time-limited < 2 weeks, rarely requires medical intervention; most commonly associated agents are paroxetine>fluoxetine>sertraline> fluvoxamine= citalopram= escitalopram • PPHN-Risk increased from 1-2/1000 to 6/12/1000 with exposure to SSRI after 20 weeks gestation

  49. FDA--Proposed Pregnancy and Lactation Labeling Rule • Remove ABCDX categories from ALL drugs • Standard format and content requirements • Merge “pregnancy”+ “labor and delivery” sections • Lactation section-replace “Nursing mothers” section • Require updating when new information available • Pregnancy registry contact information • Standard statement about background population risk of fetal abnormalities • Three main parts • Fetal risk summary • Clinical considerations • Data

  50. Postpartum Depression

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