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ANTEPARTUM DEPRESSION

ANTEPARTUM DEPRESSION. 10 - 13% : Major and Minor Depression (O’Hara, 1990; Gotlib et al, 1989; Kumar 1984, Evans et al 2001) Low SES and psychosocial stressors (Hopfer et al 1995) Strongest Predictor of PPD (Graff et al, 1991).

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ANTEPARTUM DEPRESSION

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  1. ANTEPARTUM DEPRESSION • 10 - 13% : Major and Minor Depression • (O’Hara, 1990; Gotlib et al, 1989; Kumar 1984, Evans et al 2001) • Low SES and psychosocial stressors • (Hopfer et al 1995) • Strongest Predictor of PPD • (Graff et al, 1991)

  2. Psychiatric Disorders during Pregnancy and the Postpartum Period Margaret Spinelli, MD Associate Prof Of Psychiatry Director, Maternal Mental Health Program

  3. ANTEPARTUM DEPRESSION • Poor Appetite;  Weight • Insomnia • Poor Prenatal Care • Nicotine, Drugs and Alcohol • (Zuckerman et al, 1990)

  4. ANTEPARTUM DEPRESSION • Low birth weight • Prematurity • Growth retardation • Small for gestational age infants • Developmental delay • (Flynn 2005; Bonari et al 2004; Kurki et al 2000; Zuckerman et al, 1990; )

  5. PRENATAL DEPRESSION AND ANXIETY • ANXIETY>>>>> UTERINE ARTERY RESISTANCE >>>> • LOW BIRTH WEIGHT • INCREASED MISCARRIAGE • PREMATURITY • FETAL HYPOXIA • (Glover and O’Connor 2002, Chung et al 2001, Wadhwa et al 1993 Teseira et al. 1999)

  6. Antenatal Anxiety: effects on the fetus and child • ALSPAC community sample • n=8,323 mother-infant pairs • Gestational Age: 32 weeks • Behavioral problems at 4 and 7 years (Glover V, 2003,BJM) ) cortisol cortisol

  7. DECISION ANALYSIS

  8. RISK / BENEFIT ANALYSIS • framed by clinician’s expertise and the patient’s values and treatment preferences • **PLAN BEFORE PREGNANCY** • (Wisner et al 2000)

  9. Antidepressant SSRIs: metanalysis • Sertraline (Zoloft) • Citalopram (Celexa) • Fluoxetine (Prozac) • no major malformations • +/- Neonatal toxicity (Sivojelezova et al; 2005)

  10. PAXIL • Retrospective Epidemiological Study • 3,581 SSRI exposed pregnant women • increased risk of major congenital malformations • (OR 2.20; 95% CI: 1.34-3.63) • increased risk for cardiovascular malformations • (OR 2.08; 95%CI: 1.03-4.23) • Ventricular Septal Defect. (10/14) • (GSK: 2005)

  11. TRICYCLICS (TCAs) • Desipramine (DMI) • Nortryptylline(NTP) • Serum levels • Neonatal toxicity +/- • Withdrawal sx. • Anticholinergic effects

  12. Neurodevelopment: TCA or SSRIs through fetal life • Mother- child pairs (15-71 mos.): • Tricyclics: (n = 46) • Fluoxetine: (n = 40) • Control: (n = 36) • Results: TCA or SSRI: • NO difference in IQ (Baylor or Mc Carhty scales), • temperament, language, or behavior • Depression: duration>>>> low IQ episodes>>>> poor language development • Nulman et al 2002

  13. “Neonatal Withdrawal Syndrome” Databases of adverse drug events • WHO Collaborating Center for Drug Monitoring • ID 74 Cases of “Neonatal Withdrawal Syndrome” • tremor, neonatal convulsions, abnormal crying • (paroxetine (n=51), fluoxetine (10), sertraline (7), citalopram (6), venlafaxine (6) • (Sanz et al; The Lancet, 2005) • FDA Adverse Event Reporting System • 57 cases of neonatal withdrawal • (paroxetine (n=35), fluoxetine (4), sertraline (8), citalopram (5), venlafaxine (3), fluvoxamine (2) (CDER: 2004, meeting document)

  14. SSRI Neonatal WD: Case Reports • 18 cases of SSRI • 61% Paxil; 22% Prozac • Exposure • (17-40 weeks gestation; median 40 wks) • Onset of symptoms: • Tremor, increased muscle tone, irritability, resp distress • birth to 3 weeks • Duration of symptoms: • mean: 2 weeks • SSRIs: • (paroxetine (n=11), fluoxetine (4), sertraline (1), citalopram (1), venlafaxine (1) • (Moses-Kolko et al; JAMA, 2005)

  15. Meta-analysis: 3rd TM exposure to SSRIs • Neonatal Behavioral Syndrome; • Meta-analysis: 3rd TM: ( 9 cohort studies and 18 cases) • Risk Ratio : 3.0 (95% CI, 2.0-4.4) • CNS, motor, respiratory and GI signs • Usually mild and time limited (2 weeks) • Managed with supportive care • Most involve fluoxetine and paroxetine • More severe: seizures, hyperpyrexia etc. • (Moses-Kolko et al. JAMA, 2005)

  16. Neonatal Adaptation after 3rd TM exposure to SSRIs Neonatal Behavioral Syndrome; Special Care Nursery Admissions: 2.6 (95% CI, 1.4-4.7) Overall respiratory difficulty: 2.3 (95% CI, 1.6-3.2) • Incidence of Intubation: 0.3% (1/313) • No neonatal deaths • (Moses-Kolko et al. JAMA, 2005)

  17. SSRIs and Persistent Pulmonary Hypertension of the Newborn 377 Infants born with PPHN 14 infants with late (>20 weeks) SSRI exposure were compared to 6 control infants with early (<20 weeks) or no exposure to SSRI. Odds of PPHN with late exposure compared to early or no exposure : 6.1 (95% CI, 2.2-16.8) (Chambers et al, NEJM, 2006)

  18. Absolute Risk of PPHN • Limitations: • supports association; no cause effect relationship • small Ns • retrospective RR = 6.1 (95% CI, 2.2-16.8) Absolute Risk = 6-12/ 1000 births (0.6-1.2%) Therefore 99% of women treated with an SSRI delivered infants without PPHN

  19. How should these reports impact clinical practice?

  20. Recurrence Risk of MDD in women who discontinue antidepressant treatment proximal to conception Group Relapse Discontinued 44/65 (68%) Maintained 21/82 (25%) Time to recurrence: 50% in 1st TM / 90% in 2nd TM (Cohen et al; JAMA, 2006)

  21. ELECTROCONVULSIVE THERAPY • APA guidelines: • Ob consult • Gest age >10 weeks • Maternal and fetal heart rate • Ob present if high risk • Faculties for fetal emergencies • Monitor fetal movement

  22. Herbals • NO CLINICAL DATA • St John’s Wort • SAMe • Valerian Root • +/- • Omega 3 Fatty Acids

  23. Alternatives • Acupuncture • (n=61) • Active acupuncture, v. control acupuncture vs. massage • Response rates 69% v.47% v.29% • (Manber et al 2004) • VNS

  24. Light Therapy for Pregnant Depressed Women Mean Depression Scores Weeks of Light Therapy Oren D, Wisner K, Spinelli M et al, 2002

  25. There are no clinical guidelines for effective treatment for antepartum depression.

  26. Interpersonal Psychotherapy forAntepartum Depression (IPT-P) • (Spinelli and Endicott Am J Psychiatry 2003, 160:555-562) • NIMH Grant #1K20 MH01276-01

  27. DEMOGRAPHICS(N=38) • AGE: 29.I0 ( + 6.20) • GESTATION: 21.40 WKS. ( +7.20) • INCOME: • 50 % $5-25,OOO • 16% $25-40,000 • RACE: • LATINO : 66% ( 80% SPANISH SPEAKING) • AFRICAN AMERICAN: 5% • CAUCASIAN: 29%

  28. 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 WomenEdinburgh Postnatal Depression Scale(p=.005) EPDS >>>more depressed IPT-P Phase

  29. 26 PEP IPT-P 24 22 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 WomenMean HAM-D(p=.021) HAM-D IPT-P Phase

  30. 60 50 40 30 20 10 0 IPT-P PEP Clinical Global Impressions Recovery < 2(P=.O11) Frequency (%)

  31. ANTEPARTUM INTERPERSONAL PSYCHOTHERAPY AT 3 NEW YORK CITY SITESNIMH Grant #RO1 MH 069915-01A2

  32. DESIGN AND METHODS NIMH 5 Year Clinical Treatment Trial • Focus: Psychiatry into primary care • Treatment in OB department • 3 NYC sites • 3 MFM faculty: co-PIs • Dr. Jane Cleary-Goldman (Columbia) • Dr. Robin Kalish (Cornell) • Dr. Lois Brustman (St.Luke’s Roosevelt Hospital)

  33. AIM Assess the efficacy of a 12-week bilingual treatment trial of Interpersonal Psychotherapy for Antepartum Depression vs. Parenting Education Program for multi- ethnic/racial sample from 3 NYC sites

  34. Antepartum Interpersonal Psychotherapy at 3 NYC Sites • detect and treat antepartum depression • prevent postpartum depression • assess maternal fetal/ infant attachment • evaluate feasibility of services as they relate to race, ethnicity and SES ($50/visit)

  35. WHEN BONDING FAILS..

  36. Poor Response to Infant Cues/ Lack of Warmth Insecure Attachment, Irritable (Biringen and Robinson, 1991; Zuckerman et al, 1990) Behavior Problems, Delayed Language Easily Angered (Murray, 1991; Biringen and Robinson, 1991) Intellectual Deficits, Predisposition to Depression (Cogill et al, 1986; Weissman et al, 1987) Depressed mother; Depressed child

  37. Epidemiology of Postpartum Episodes

  38. Postpartum Depression • Prevalence: 10-20% • Across cultures • (Kumar 1994) • Risk Factors: • Personal and Family H/O depression • Prenatal depression** • Prominent symptoms: • anxiety associated with distressing thoughts about infant safety • Feelings of guilt and inadequacy about mothering • Inability to sleep when infant sleeps • lack of interest in baby, family or activities • anxiety as bizarre thoughts and fears • poor bonding, feel “detached” “numb” • Thoughts of death or suicide • (DOH;OMH 2005; Flynn, 2005) )

  39. Treating Postpartum Depression • Fluoxetine (Prozac): Controlled trial • Sertraline (Zoloft); open • Venlafaxine (Effexor): open • Interpersonal Psychotherapy • Fluoxetine and CBT

  40. Guidelines for Medicating during Lactation • Avoid polypharmacy • Monitor infant sleep, feeding • Bottle feed if sick • Lowest effective dose • Collaboration with Pediatrician • All pass to breast milk • depends on drug and metabolite • UK outcome on physiology, behavior and development

  41. Benefits of Breastfeeding Provides immunity Allergies, asthma Otitis media Viral diarrhea RSV morbidity Upper and lower respiratory infection Childhood lymphoma, Type I DM, Crohn’s IQ: 8-12 points

  42. BREASTFEEDING AND ANTIDEPRESSANTS • SSRIs: first line • Few adverse effects to date • Infant serum: minimal or no drug or metabolite*** • TCAs: second line • NTP (least detected in infant serum) • Limitations: • Small Ns, case reports, no long term effects • ***does not apply to fluoxetine/ venlafaxine

  43. BREASTFEEDING AND ANTIDEPRESSANTS • Celexa: • Elevated infant levels • ‘uneasy sleep” • Serum Fluoxetine accumulation • long T ½: accumulation in infant serum • Immature infant enzymes • Irritability

  44. BREASTFEEDING AND ANTIDEPRESSANTS • Sertraline • usually yields undetectable infant serum levels • No adverse effects • Maternal 5HT concentration decreased with sertraline but infant platelet 5HT transport not affected c/w undetectable levels in infant serum. • (Epperson 2003)

  45. BENZODIAZEPINES AND LACTATION • Neonatal Risks (Burt et al. AJP 2001) • withdrawal, sedation, cyanosis • Guidelines • low dose, monotherapy • split dosing • discard feeding at peak drug level; • formula supplementation • short-acting, low metabolites • Alternative: • Nortryptylline (NTP)

  46. POSTPARTUM PSYCHOSIS • auditory hallucinations (baby; religious) • visual hallucination (seeing or feeling a presence) • agitation, irritability • paranoid delusions • delirium (waxing and waning) • confusion • mania • suicidal or infanticidal thoughts • bizarre delusions

  47. POSTPARTUM PSYCHOSISHIPPOCRATES 4TH CENTURY “LACTATIONAL PSYCHOSIS” • PREVALENCE • 1-2/1000 • 70% IN THE FIRST 2 WEEKS • BIPOLAR EPISODE **** • (<5% SCHIZOPHRENIA) • QUALITIES • ORGANIC SYMPTOMS • WAXING & WANING/ AMNESIA RISK:INFANTICIDE • RECURRENCE: 30-50% • “PROPHYLAXIS”: PP LITHIUM OR OTHER

  48. “Cognitive Disorganization/Psychosis”(PPP)(Wisner et al; 1994) • delirium; Impaired Sensorium • cognitive disorganization • visual, tactile and olfactory hallucinations • bizarre behavior • self-neglect Waxing and waning presentation ***Psychiatric emergency***

  49. PPP is BPD??(Chaudron 2003) • Bipolar women • high risk for postpartum episode • (Liebenluft ‘96) • highest rates of PPP in general population • (Jones and Craddock 2001, Reich and Winokur, 1970) • high rates of PP relapse • (Marks et al, 1992, Dean et al. 1989) • FH of PPP • (Jones and Craddock 2001, Reich and Winokur, 1970, Dean et al, 1989))

  50. NEUROHORMONES & CNS Estrogen  TRYP 5HT 5HT Re-uptake Site E2  PROG  MAO / COMT MAO: Monoamine Oxidase COMT: Catechol-O-Methyl Transferase E2  MAO & COMT   5HT PROG  MAO & COMT   SHT

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