Postpartum Psychiatric Illness: Early Detection, Treatment, and Prevention

1. Postpartum Psychiatric Illness: Early Detection, Treatment, and Prevention Lee S. Cohen, M.D.

2. Pregnancy Risk of Psychiatric Illness During Pregnancy and Postpartum Period 60 50 40 Admissions Per Month 30 20 10 -2 Years -1 Year Childbirth +1 Year +2 Years Kendell et al. Br J Psychiatry. 1987;150:662

3. Spectrum of Postpartum Mood Disorders Postpartum Psychosis Postpartum Depression (10-15%) Postpartum Symptom Severity Postpartum Blues(50-85%) None

4. Postpartum Blues • 50-85% of women • Within first two weeks after delivery • Mood lability, tearfulness, anxiety and sleep disturbance • Minimal or no impairment of functioning • Time limited • No specific treatment required

5. Postpartum Depression • Major and minor depression occurs in approximately 10% of women after live childbirth; range 5% to 15%1-4 • May have acute early onset (within days) but symptoms typically emerge over time (within 3 months postpartum)5 • Often underdiagnosed and undertreated5 • Significant risks to mother and child if left untreated6 • O’Hara MW, et al. J Abnorm Psychol. 1984;93:158-171. • O’Hara MW, et al. J Abnorm Psychol. 1991;100:63-73. • Kumar R, Robson RM. Br J Psychiatry. 1984;144:35-47. • Kendall K, et al. Br J Psychiatry. 1987;150:662-673. • Nonacs R, et al. J Clin Psychiatry. 1998;59(suppl 2):34-40. • Lyons-Ruth. Harv Rev Psychiatry. 2000;8:148-153. • Cogill SR, et al. Br Med J. 1986;292:1165-1167. • Murray L, et al. Child Dev. 1996;67:2512-2526.

6. Puerperala Depression as a Distinct Diagnostic Entity ? • Prevalence of PPD is similar to non-puerperal MDD • Similar clinical presentation • Vulnerability to recurrent non-puerperal and puerperal depression • Similar response to antidepressant treatment

7. Psychiatric History Predicts Risk of Depression in the Postpartum Period 60 50 40 Incidence (%) 30 20 10 0 Risk in general History of major History of postpartum depression 2 depression 2 population 1 • O’Hara MW, et al. J Abnorm Psychol. 1984;93:158-171. • O’Hara MW, et al. Postpartum Depression: Causes and Consequences. New York, NY: Springer-Verlag; 1995.

8. Postpartum Anxiety Disorders • Postpartum panic disorder • Postpartum OCD : can be seen in the absence of PPD • Comorbid depression and anxiety commo

9. PPD: Obsessions and Compulsions • Intrusive obsessional thoughts common • Thoughts of doing harm to infant • Obsessions more common in PPD (57%) than in non-puerperal MDD (36%) Wisner et al, 1999

10. Postpartum Psychosis • Rare, occurs in 1 to 2 per 1000 pregnancies • Rapid, dramatic onset within first 2 weeks • Resembles an affective (manic) psychosis • Early signs: sleep disturbance, restlessness • Depressed or elated mood, agitation, delusions, depersonalization • Risk of self-harm and harm to infant

11. What is the relationship between PPD and Bipolar Disorder ?

12. Bipolarity in Postpartum Depression • Increased risk for PPD in women with bipolar disorder • Early age at illness onset • Recurrent depressive episodes (>3) • Brief episodes of MDD (<3 months) • Hyperthymic personality • Antidepressant-induced hypomania/mania • Non-response to 3 or more antidepressants Ghaemi et al, 2002

13. High Risk for Postpartum Psychosis Among Women With Bipolar Disorder • forme fruste of bipolar disorder • Symptoms usually appear acutely within 48 hours to 2 weeks after delivery • Psychiatric emergency • Estimated risk for bipolar patients is 20%–30% (baseline risk in general population is 0.1%–0.2%) Chaudron LH, et al. J Clin Psychiatry. 2003;64:1284-1292.Jones I, Craddock N. Am J Psychiatry. 2001;158:913-917.

14. Postpartum Psychosis: Further Evidence for a Bipolar Connection • Family studies: postpartum psychosis • Clusters in families multiply affected with bipolar disorder • Clusters in families multiply affected with postpartum psychosis • Genetic studies: • Postpartum psychosis susceptibility linked to variation at the serotonin transporter Jones I, Craddock N. Am J Psychiatry. 2001;158:913-917.Coyle N, et al. Lancet. 2000;356:1490-1491.

15. Longitudinal Course of Postpartum Psychosis • 95 % affective psychosis (bipolar disorder or schizoaffective disorder) • 5 % schizophrenia • Recurrence of affective episodes is the rule though circumscribed illness may be seen Terp et al, 1999

16. Postpartum Psychiatric Illness: Implications for Early Detection • Symptoms of postpartum depression may be difficult to distinguish from normative postpartum symptoms (sleep & appetite disturbance, loss of libido) • Multiple contacts with health care providers • PPD is frequently missed: role of obstetrician, pediatrician

17. The MOTHERS Act(S. 1375) Mom’s Opportunity to Access Help, Education, Research and Support for Postpartum Depression Act • “To ensure that new mothers and their families are educated about postpartum depression (PPD), screened for symptoms, and provided with essential services, and to increase research at the National Institutes of Health on postpartum depression.” • Proposes to institute a program of grants to establish, operate, and coordinate educational programs and health care services • Current status: Bill has been referred to the Committee on Health, Education, Labor, and Pensions

18. Edinburgh Postnatal Depression Scale (EPDS) • Screening tool for postpartum depression • Validated in diverse populations • 10-item self-rated questionnaire • Score of > 12 suggestive of depression • Suicidal ideation requires further evaluation Cox et al, Br J Psychiatry 150:782-786.

19. Screening for PPD • Screening and early intervention • Most women not identified • Goal is to screen women at highest risk • Late identification increases risk • What is the ideal screening tool? Nonacs R, Cohen, L. Postpartum Psychiatric Syndromes. In: Sadock B, Sadock A, ed. Comprehensive Textbook of Psychiatry. Philadelphia: Lippincott Williams and Wilkins; 2000:1276-1283.

20. Postpartum Depression Predictors Inventory • Stronger Predictors: • History of depression • Depression in pregnancy • Anxiety in pregnancy • Stressful life events • Marital dissatisfaction • Child care stress • Inadequate social supports • Difficult infant temperament • Low self-esteem • Weaker Predictors: • Unwanted or unplanned pregnancy • Lower socioeconomic status • Being single • Postpartum blues

21. Postpartum Mood Disorders:Etiology

22. Psychosocial Variables PPD Hormonal Factors Genetic Vulnerability

23. Risk for PPD: Hormonal Factors • Inconsistent findings • Thyroid dysfunction is common in PPD • No correlation with absolute concentrations of gonadal steroid • Behavioral sensitivity to gonadal steroids in women with PPD Bloch 2000

24. Postpartum Mood Disorders:Treatment

25. Treatment of Depression in the Postpartum Period: Psychotherapy IPT=interpersonal psychotherapy; CBT=cognitive behavioral therapy;  =decrease; RCT=randomized, controlled trial. 1. O'Hara MW, et al. Arch Gen Psych. 2000;57:1039-1045. 2. Stuart S, et al. J Psychother Pract Res. 1995;4:18-29. 3. Appleby L, et al. BMJ. 1997;314:932-936. 4. Wickberg B, Hwang CP. J Affect Disord. 1996;39:209-216.

26. Postpartum Depression: Pharmacologic Treatment Fluoxetine Appleby, 1997 Double-Blind Paroxetine Misri, 2004 Double-Blind Sertraline Wisner, 2006 Double-Blind Nortriptyline Wisner, 2006 Double-Blind Sertraline Stowe, 1995 Open Fluvoxamine Suri, 2002 Open Venlafaxine Cohen, 2001 Open Bupropion Nonacs, 2004 Open

27. Week 4 Week 4 Base End Base End Week 4 Base End Venlafaxine for PPD: Treatment Response 5 25 25 20 4 20 15 3 15 ** ** 10 2 10 * ** * 5 1 5 * 0 0 0 Ham-D * = p<.0001 ** = p<.0001 KellnerAnxiety * = p<.0001 ** = p<.0001 CGI * = p<.0001 ** = p<.0001 Cohen LS et al, 2001. J Clin Psychiatry 62:592-596.

28. Postpartum Depression: Comparing Treatment Response 100 Response • Most studies on serotonergic agents • SSRIs and TCAs have similar efficacy • Bupropion may be less effective Remission 80 60 % of Patients 40 20 0 SERT OPEN VEN OPEN BUP OPEN Stowe ZN, et al. Depression. 1995;3(49):55. Cohen LS, et al. J Clin Psychiatry. 2001;62(8):592-596. Nonacs RM, Unpublished data.

29. Postpartum Depression: Pharmacologic Strategies • Data to support use of serotonergic agents (sertraline, fluoxetine, venlafaxine, fluvoxamine) and TCAs (nortriptyline) • Other antidepressants may be effective • Adequate dosage • Adequate duration of treatment (>6 months) • Adjunctive anxiolytic agents (lorazepam, clonazepam)

30. Treatment of Bipolar Depression During the Postpartum Period • No treatment studies in literature • Mood stabilizers (lithium, lamotrigine) • Atypical anti-psychotics may be helpful • Antidepressants may exacerbate mood and should be used with caution

31. Postpartum Depression: Is there a Role for Hormonal Treatment ? • Progesterone: Inconsistent findings • Progesterone may exacerbate mood symptoms ? • Estrogen: Beneficial alone or as adjunct to antidepressant Gregoire 1996, Ahokas 2001

32. Estrogen for Postpartum Depression • 61 women with PPD (37 active, 24 placebo) • Transdermal 17 -estradiol • 47% on antidepressants at study entry • Treatment effect within 1st month, estrogen decreased EPDS by 4.38 points at 12 wks • At 12 wks, 80% on estrogen no longer depressed (<14 on EPDS) vs. 31% in placebo group • No evidence of uterine hyperplasia Gregoire, 1996

33. Estrogen for Postpartum Depression • 23 women with PPD (mean MDRS 40.7) • All women with low serum estradiol (mean 79.8 pmol/L) • Sublingual 17 -estradiol • After 2 wks, 19/23 (83%) with clinical recovery (mean MDRS 11.0) Ahokas, 2001

34. Postpartum Psychosis: Treatment • Psychiatric /Obstetric emergency • Treat as an affective psychosis (antipsychotic ( atypical/typical), mood stabilizer, benzodiazepines) • ECT is rapid and effective • Duration of treatment not well established • Need for maintenance treatment in patients with recurrent affective disorder

35. Psychotropic Medications in Breast-Feeding Mothers

36. Psychotropic Medications and Breast-Feeding • About 50% of women nurse their infants • Benefits: nutrition, immunity, cognitive development • All medications are secreted in breast milk • Concentrations in breast milk vary • Adverse events in infant are rare • Decisions made on a case by case basis

37. Which Antidepressant is the Best ? The one that is likely to work the best • Continue antidepressant used during pregnancy • Use agent to which patient has responded to in the past • Sertraline, paroxetine, nortriptyline well-characterized, no adverse events

38. Prevention of Postpartum Illness

39. Identification of women at high risk for postpartum psychiatric illness • Is this disorder preventable?

40. Stratification of Risk LOW HIGH

41. Risk of Relapse Following Lithium Discontinuation Postpartum (Weeks 41–64) Pregnancy (Weeks 1–40) 100 (n=25) 90 80 70 60 (n=42) % Remaining Stable 50 40 (n=59) 30 (n=20) 20 Nonpregnant Nonpregnant 10 Postpartum Pregnant 0 0 4 8 12 16 20 24 28 32 36 40 44 48 52 56 60 64 Weeks at Risk Off Lithium Viguera AC. Am J Psychiatry. 2000;157:179-184.

42. Non-Pharmacologic Prophylaxis • Positive effect of IPT during pregnancy • 13 women with depression during pregnancy • IPT induced remission in all • No women developed PP Spinelli 1997

43. Pharmacologic Prophylaxis: Postpartum Major Depression • Antidepressant treatment in women with history of PPD: equivocal results • Open study with TCAs and SSRIs showed reduction in risk (Wisner 1994) • Placebo-controlled study with NTP negative(Wisner 1999) • Placebo-controlled study with sertraline positive(Wisner 2004)

44. Depression in Women Treated with Postpartum Sertraline or Placebo • Non-depressed women with hx of PPD (n=22) • Randomized to sertraline (up to 75mg) or placebo • Drug started after delivery • Drug tapered at week 17 Wisner KL et al, 2004. Am J Psychiatry 161:1290-1292.

45. Postpartum Prophylaxis for Women with Bipolar Disorder

46. Puerperal psychosis/ Bipolar disorder + Austin, 1992 + Van Gent, 1992 Bipolar disorder Bipolar disorderUnipolar depression + Abou-Saleh, 1983 + Stewart et al, 1991 Mixed diagnoses + Cohen et al, 1995 Bipolar disorder Postpartum Lithium Prophylaxisfor Bipolar Women Lithiumbenefit Subjects (Dx)

47. Valproate +/- Wisner, 2004 Bipolar disorder Puerperal psychosis/Bipolar disorder Sharma , 2006 olanzapine + Postpartum Prophylaxis with Mood Stabilizers other than lithium Subjects (Dx) Benefit Wisner KL et al Biol Psychiatry 2004;56:592-596; Sharma V et al. Bipolar Disord 2006;8:400-4

48. Prophylaxis (N=14) No Prophylaxis (N=13) Postpartum Prophylaxis in Bipolar Women Cumulative Survival Prophylaxis (N=14) No Prophylaxis (N=13) Time (Weeks) Significant difference between groups(Peto-Peto-Wilcoxen 2=6.966, df=1,p<0.01) Cohen LS, Sichel DA, et al. Am J Psychiatry. 1995.

49. Postpartum Mood Disorders:Long Term Impact

50. Impact of Maternal Depression on Child Well-Being • Delays in cognitive development • Increased risk of behavioral problems • Infants: sleep problems • Toddlers: temper tantrums • School age: anxiety, inattention, hyperactivity, aggression, poor school performance • Insecure attachment, emotional dysregulation • Risk for child abuse and neglect Atkinson L et al. Clin Psychol Rev. 2000;20:1019-1040. Murray L, Cooper PJ. Arch Dis Child. 1997;77:99-101.