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Update on Perinatal Mood Disorders William Watson, MD, FCFP Family Physician, St. Michael’s Hospital Simone Vigod, MD, MSc, FRCP(C) Staff Psychiatrist,

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Presentation on theme: "Update on Perinatal Mood Disorders William Watson, MD, FCFP Family Physician, St. Michael’s Hospital Simone Vigod, MD, MSc, FRCP(C) Staff Psychiatrist,"— Presentation transcript:

1 Update on Perinatal Mood Disorders William Watson, MD, FCFP Family Physician, St. Michael’s Hospital Simone Vigod, MD, MSc, FRCP(C) Staff Psychiatrist, Women’s College Hospital ASA, Toronto November 30, 2013 1

2 Objectives To learn about updated risk factors for perinatal mood disorders in the family practice context To learn about prevention and treatment of depressive and bipolar disorders in pregnancy and the postpartum period 2

3 Faculty/Presenter Disclosure Faculty: Dr. Bill Watson and Dr. Simone Vigod Program: 51 st Annual Scientific Assembly Relationships with commercial interests: NIL

4 Disclosure of Commercial Support Dr. Watson has received some financial support from the OCFP in the form of an honorarium, and has no financial disclosures or conflicts of interest related to this presentation Dr. Vigod receives salary support from the Ontario Mental Health Foundation (New Investigator Fellowship), Women’s College Hospital and Research Institute (Shirley-Brown Clinician Scientist), and the Dept. of Psychiatry, University of Toronto She receives operating funds from the Canadian Institutes of Health Research (CIHR), the Schizophrenia Society of Ontario and the Ontario Ministry of Health and Long Term Care (MOHLTC) She has no financial disclosures or conflicts of interest to declare relevant to this presentation. Potential for conflict(s) of interest: NIL

5 Mitigating Potential Bias There is no source of potential bias and no support or funding from pharmaceutical companies

6 Case 1: Sarah 6 29-year-old, married, real estate agent Had a depressive episode 2 years ago where she lost interest in work and quit her job, which negatively affected her interpersonal relationships as well No evidence of bipolarity, no history of psychosis or safety issues You treated her successfully with sertraline, and she has reached remission She and her new husband plan to try to become pregnant imminently She asks you if this is the right time to discontinue her antidepressant

7 Case 2: Maria, aged 22 Maria, G1P1, five-day-old baby boy - checkup. – Normal pregnancy and delivery, baby is healthy but has lost 100 g since birth. Maria is breastfeeding and having difficulty with the baby’s latch, and she thinks she doesn’t produce enough milk. She looks very tired and on the verge of tears. – Maria says she hasn't been out of the house since the baby was born, and that she has been crying frequently. She worries about the house being a mess when visitors arrive. – John, the baby’s father, accompanies them. John is bewildered by her tears and asks you if her tearfulness is normal. He is concerned about how she is feeling and quietly asks if she is depressed. What is the next step?

8 Case 3-Mrs. C A 35 year old teacher Brought to the office by her husband of 10 years He has noticed that since the birth of their one month old daughter, Mrs. C. has not been her normal self-he is worried Mrs. C starts to cry after you ask her about the baby – She feels overwhelmed, a bad mother, and especially guilty about having had a baby – Most of the time she is irritable and anxious Personal hx of abusive (psychological) mother You note she is tearful, frustrated, poor mother- infant interaction

9 Why know about perinatal mood disorders? An important public health issue – Risk of a Major Depressive Episode is up to 10% in pregnancy, 15% postpartum (higher than age- matched point prevalence in the non-pregnant population) – Risk of bipolar disorder relapse is high in pregnancy and very high in the postpartum period

10 Why know about perinatal mood disorders? Potential Impact of untreated mood disorders on mother, baby and family can be profound: – Pregnancy: spontaneous abortion, poor prenatal care, substance use, poor fetal growth, preterm labour, suicide – Postpartum: poor attachment/parenting, delayed infant motor, language and cognitive development, child behaviour problems, suicide/infanticide

11 Still face experiment www.youtube.com/watch?v=apzXGEbZht0‎

12 Spectrum of Illness Entire range of psychiatric disorders occur during the perinatal period – Perinatal period generally defined from onset of pregnancy until ~ 1 year postpartum NOTE: DSM-5 defines perinatal onset for mood disorders as being onset during pregnancy or within 4 weeks postpartum – Management often begins at pre-conception counseling for women with a personal history of mental health problems

13 Management of Perinatal Mood Disorders Prevention – Decision-making related to relapse risk, follow-up plans, psycho-education re: need for sleep and good social support Treatment – Safety Assessment – Risk-benefit analysis: safety of treatment during pregnancy/lactation vs. risks of untreated illness – Options: Psychotherapy, Psychotropic Medication, ECT, Novel somatic treatments

14 Context in Family Practice Hospital/office setting Well baby, well family exam Other family members/relationships Resources

15 Screening tools National Institutes for Clinical Excellence (NICE) During the past month, have you often been bothered by feeling down, depressed or hopeless? During the past month, have you often been bothered by having little interest or pleasure in doing things? If the woman answers 'Yes' to both questions a further question should be asked: Is this something you feel you need or want help with? Edinburgh Postnatal Deperssion Scale (EPDS) In the past seven days: I have been able to laugh and see the funny side of things I have looked forward with enjoyment to things I have blamed myself unnecessarily when things went wrong I have been anxious or worried for no good reason I have felt scared or panicky for no very good reason Things have been getting on top of me I have been so unhappy that I have had difficulty sleeping I have felt sad or miserable I have been so unhappy that I have been crying The thought of harming myself has occurred to me Scored 0-30. Scores > 13 associated with 10x likelihood that patient has major depression

16 PHQ 2 and 9 may detect PPD at well baby visits (Cochrane 2013) 82% sensitivity, 84% specificity Compares favorably with EPDS May be effective in screening for PPD PHQ-2=During the past 2 weeks, how often have you been bothered by: – Little interest or pleasure in doing things (0-3) – Feeling down, depressed or hopeless (0-3) – If score > 3, use PHQ-9

17 Why do postpartum mental health problems go undetected? Normal vs abnormal? Guilt around depression Little preparation for postpartum Lack of recognition by peers and professionals Some women hide depression very well

18 Mood Disorders in Pregnancy

19 Not necessarily a high risk time for new onset – Although, in general, the 3 rd and 4 th decades of life are high risk for onset of mood disorders in women – Unplanned pregnancy, marital or financial instability may pose risk Relapse rates of existing disorders are high – Risk Factors for Relapse (Viguera 2011) Younger age at onset Previous postpartum episodes Fewer years of illness Bipolar disorder Fewer children, and Not being married

20 68% Proportion of Pregnant Women Remaining Euthymic 4036322824201612840 0.0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1.0 Maintained Rx (n=82) Discontinued Rx (n=65) HR: 5.0 (2.8-9.1) Cohen et al. JAMA 2006;295(5):499-507. Weeks of Gestation 26% Relapse of Major Depression when Antidepressants are Discontinued

21 Unipolar Depression in Pregnancy But…. In the Cohen et al. study, the overall relapse rate was 43% and ~ 75% of the women had 3+ prior episodes of depression

22 Unipolar Depression in Pregnancy In a sample that included women who were less severely ill Yonkers et al., 2011 – Relapse rate = 16% – Women with 4 or more episodes before pregnancy were at highest risk of depression in pregnancy – Discontinuation of antidepressants in pregnancy did not have a strong effect on the development of a major depressive episode 22

23 Unipolar depression in pregnancy Take Home Points: 1.History of recurrent depression increases risk of depression in pregnancy 2.Severity may be an effect modifier with respect to medication discontinuation: In women with severe and/or recurrent depression, discontinuation of medication represents risk of relapse In women with less severe histories of depression, the impact of medication discontinuation may not be as dramatic 23

24 Psychotropics Pregnancy – 3 theoretical risks of meds Teratogenesis (1 st trimester exposure usually) Neonatal toxicity or withdrawal (3 rd trimester) Developmental effects with latent childhood manifestations Lactation – Passage into breast milk and theroretical risk of toxicity in the infant

25 Risk/Benefit Primer Maternal Depression SSRI/SNRI Medication (likely class effect)  Negative effects of depression on daily function, sense of well being, experience of pregnancy  Factors associated with depression that may impact fetal outcomes: reduced antenatal care attendance, smoking, substance and alcohol use  Increased risk of postpartum depression  Possible negative effects on child in infancy and early childhood Evidence for marginally increased risk of:  Spontaneous abortions (TM1)  Preterm birth (no high risk of < 36 weeks)  Lower birthweight (only by 200-300g)  Lower APGAR scores  Cardiovascular malformations (TM1) ARI 5/1000 to ~ 8/1000 Likely class effect despite early focus on paroxetine  Neonatal persistent pulmonary hypertension AOR~2 in cohort studies (6 in case- control) for TM 2 exposure ARI 1.2/1000 to ~3/1000 25 Yonkers, K. A., Wisner, K. L., Stewart, D. E., Oberlander, T. F., Dell, D. L., Stotland, N., … Lockwood, C. (2009). The management of depression during pregnancy: a report from the American Psychiatric Association and the American College of Obstetricians and Gynecologists. American Psychiatric Association, 114, 703-713.

26 Neonatal Adaptation Syndrome Set of neurobehavioral signs occurring ~ 30% of SSRI/SNRI exposed full term babies vs. 10% of non exposed babies Possible symptoms – Usually mild: Insomnia or somnolence ; Agitation, tremors, jitteriness, shivering and/ or altered tone; Restlessness, irritability & constant crying; poor feeding, vomiting/diarrhea – Severe syndrome that consists of seizures, dehydration, excessive weight loss, hyperpyrexia (poor temperature control), or intubation (due to tachypnea/respiratory distress) is rare in term infants (1/313 quantifiable cases)* Duration Usually short lived – Median duration of 3 days, and 75 % complete resolution by 5 days (max 4 weeks)’ – Premature babies are more vulnerable to NAS, and are more likely to develop signs, which may be more severe. – Weak evidence that severity of symptoms may be dose related Management supportive 26 Neonatal Signs After Late In Utero Exposure to Serotonin Reuptake Inhibitors. Moses-Kolko et al.JAMA 2005; 293; 2372-2383

27 Psychotherapy in PMD In general, psychosocial and psychological treatments without meds are recommended as first- line treatment of antenatal depression Evidence that individual psychotherapy may be useful in women with mild-moderate symptoms (IPT and CBT have best evidence) Takes time… while fetus may be exposed to effects of illness Need access and resources!

28 Antidepressant Medication SSRI or SNRI is first line treatment for moderate to severe depression – No evidence for preferred treatments based on effectiveness or safety, but most safety data on older SSRI/SNRIs – Usually no need to change dose for pharmacokinetic reasons – Sertraline and Paroxetine usually undetectable in serum of breastfed infants, Others < 10% passage but no adverse events reported < 20% of women accept treatment – Misinformation about risks (untreated illness and treatment) – Stigma/Pressure from family, friends, media and providers 28

29 Other antidepressants Other first-line antidepressants – E.g. Bupoprion, Mirtazapine – Much less data than SSRI/SNRIs, but nature and magnitude of risks likely similar Tricyclic Antidepressants – No clear concerns about teratogenicity, but withdrawal syndromes occur in neonates – Blood levels can be monitored through pregnancy and will likely require dosage increases as pregnancy progresses, although clinical assessment is a better marker of response than blood levels 29

30 Benzodiazepines May be required for concurrent management of anxiety and/or sleep in severe cases Contradictory data on increased risk of cleft palate/lip with 1 st trimester exposure – Best to avoid in 1 st trimester Theoretical risk of neonatal withdrawal and of toxicity in breast-feeding – Use shorter half-live drugs – lorazepam, clonazepam – Monitor infants 30

31 ECT Efficacious, but has side effects and requires general anesthetic Risk is minimal but not non-existent – Case reports suggest potential associations with adverse cardiovascular events and some adverse neonatal outcomes Use in pregnancy usually limited to: severe treatment- resistant depression, acute suicidality, psychotic depression, or severe dehydration/malnutrition secondary to a depressive syndrome 31

32 Alternative Treatments If there is benefit, then it is likely for women with mild depressive illness – Limited support for some non-pharmacologic alternatives to psychotherapy: Dietary calcium, Exercise, Massage therapy, Bright light therapy Early enthusiasm for omega-3 fatty acids – Most randomized clinical trials to date have failed to show that the active treatment differs from placebo 32

33 Alternative Treatments Repetitive Transcranial Magnetic Stimulation (rTMS) – Investigated widely for severe or treatment-resistant depression – Magnetic fields have been associated with increased risk of miscarriage --- there is a theoretical risk to administering transcranial magnetic stimulation in pregnant women – However, it is under study in pregnant populations There is a clear need for safe and rapidly effective treatments for women with depression in pregnancy 33

34 Bipolar disorder in Pregnancy Relapse risk high – 25-75% depending on population studied – Up to ¾ episodes depressed/mixed and ½ in 1 st trimester (for women euthymic at conception) (Viguera 2007) … and related to medication discontinuation Recurrence risk two-fold greater in those who discontinued medication with median time to recurrence 4x shorter Median time to recurrence 11 times shorter if meds discontinued abruptly vs. gradually

35 Risks of Continuing medication Weigh risk/impact of relapse vs. Potential risks of medication use 35

36 Mood Stabilizers Lithium – Only slightly increased risk of cardiac defects (e.g. ebstein’s anomaly) when used in pregnancy – Need to attend to ECF changes in pregnancy AND massive ECF contraction at delivery Some recommend discontinuation of Lithium with onset of labour and restart day 2 postpartum – Passes into breast milk and toxicity can be substantial therefore CLOSE monitoring if used

37 Mood Stabilizers Valproate – Teratogenic (neural tube defects - NTD) – Recent reports of developmental delay in breastfed infants Lamotrigine – Risk of NTD – Passes into breast milk (up to 30% of maternal levels)  theoretical risk of rash

38 Anti-psychotics Pregnancy: – Haloperidol best studied – not thought teratogenic – Main Issue with newer anti-psychotics is potential for weight gain and gestational diabetes – FDA warning re: Extra-pyramidal symptoms (EPS) in newborns Minimal data in breast-feeding – Clozapine and Olanzapine not recommended due to risk of blood abnormalities and EPS respectively

39 Summary re: management in pregnancy There are substantial risks to untreated mood disorders in the pregnancy Choice of treatment involves a risk-benefit analysis unique to each patient – Do not underestimate effect of decisional conflict, stigma and lack of support for women faced with these decisions about medication use

40 Postpartum mood disorders

41 Postpartum Mood Disorders Risk appears to be substantially higher than in pregnancy both for new onset and recurrent mood disorders Formulation? – Biological factors such as genetic predisposition to rapid change in hormones at delivery…. May also have medical issues (anemia, thyroid) – Psychological factors: psychodynamic considerations (e.g. history of trauma, separation-individuation, issues with dependency), personality and coping style – Social factors: social support, life stressors (e.g. health of baby, financial, intimate partner violence)

42 Date of download: 2/22/2012 Copyright © American Psychiatric Association. All rights reserved. From: Episodes of Mood Disorders in 2,252 Pregnancies and Postpartum Periods American Journal of Psychiatry 2011; 168:1179-1185 doi: 10.1176/appi.ajp.2011.11010148 Episode Occurrence Rates of Major Affective Episodes During Pregnancy and During the Postpartum Period in 1,162 Women With Bipolar I, Bipolar II, or Major Depressive Disorder a Figure Legend:

43 Postpartum Mood Symptom Spectrum Baby Blues: up to 75%, within days, resolves within first month without treatment, likely hormone-related Postpartum Depression (PPD): major depressive episode (MDD) with onset in the 1 st postpartum year (requires treatment) Postpartum Psychosis: psychotic episode, 90% occurring within first 3 months postpartum, likely a bipolar disorder presentation (*Psychiatric Emergency*)

44 Post-Partum Depression Onset: DSM 5 indicates within 4 weeks of delivery, genetics work suggests onset 6-8 weeks and clinically, even later onset observed Risk Factors: Untreated depression/anxiety in pregnancy, poor sleep, poor social support, stressful life events Symptoms: same as major depressive episode 50% with anxiety – panic, obsessive ruminations Themes of incompetence, obsessional harm (differentiate from psychosis)

45 Bipolar Disorder Postpartum Relapse 30-50% - acute and severe – mostly depressive Risk Factors (other than medication discontinuation): – Younger age, primiparity, sleep/biological rhythm disturbance – Psychosocial risk factors play less of a role Increased risk of postpartum psychosis – 90% within 4 weeks of delivery – Marked by confusion, thought disorder – Small but serious risk of suicide/infanticide

46 Back to Sarah Is this right time to discontinue her antidepressant? – Consider severity/recurrence of depressive illness (attn: to prior pregnancies/postpartum periods and premenstrual symptoms) – Consider how quickly/effectively she responds to non- pharmacological and pharmacological treatment – Consider other risk factors for poor pregnancy outcomes or relapse (e.g. medical and psychiatric comorbidity, psychosocial) – Consider gestational age of patient (i.e. planning vs. 1 st trimester) – Consider her personal preferences 46

47 Possible Plans: Sarah – Pharmacokinetic changes in pregnancy and at delivery Absorption (watch emesis) Distribution (increased ECF during pregnancy – contracts rapidly at delivery) Increased hepatic metabolism – Echocardiogram screening – Continue to monitor and plan for prevention of PPD – Counsel around potential risks of antidepressant use and NAS – Counsel patient around antidepressants in lactation 47 ContinueDiscontinue – Monitor for recurrence of illness – If illness recurs in pregnancy: consider non-pharmacologic and pharmacologic treatment strategies and potentially restart medication – Plan for prevention of postpartum depression – No clear evidence for prophylactic re-start of medication postpartum in euthymic women

48 Other considerations 1.If she elects to continue: – Would you recommend changing to a different antidepressant? – Should you reduce her dose or discontinue in 3 rd trimester to avoid NAS? 2.What if she had presented already pregnant… at 14 weeks gestation? 48

49 Case 2: Maria, aged 22 Maria, G1P1, five-day-old baby boy - checkup. – Normal pregnancy and delivery, baby is healthy but has lost 100 g since birth. Maria is breastfeeding and having difficulty with the baby’s latch, and she thinks she doesn’t produce enough milk. She looks very tired and on the verge of tears. – Maria says she hasn't been out of the house since the baby was born, and that she has been crying frequently. She worries about the house being a mess when visitors arrive. – John, the baby’s father, accompanies them. John is bewildered by her tears and asks you if her tearfulness is normal. He is concerned about how she is feeling and quietly asks if she is depressed. What is the next step?

50 Case 2-Commentary Depression vs Blues PHQ 2 = 2 Ref to Lactation consultant -Early follow-up for mom and baby

51 Case 3-Mrs. C A 35 year old teacher Brought to the office by her husband of 10 years He has noticed that since the birth of their one month old daughter, Mrs. C. has not been her normal self-he is worried Mrs. C starts to cry after you ask her about the baby – She feels overwhelmed, a bad mother, and especially guilty about having had a baby, not sleeping – Most of the time she is irritable and anxious Personal hx of abusive (psychological) mother You note she is tearful, frustrated, poor mother- infant interaction

52 Case 3 -commentary -PHQ2= 6, EPDS=20 -Mrs. C likely has postpartum mood disorder -important to discuss findings with her and her husband -make urgent referral to psych -consider using SSRI/SNRI +/- hypnotic -referral to support group -early follow up

53 Postpartum Depression Management Lifestyle and Social Support: Ensure adequate sleep, engage social supports Psychotherapy: For mild and moderate depression, evidence for interpersonal psychotherapy and cognitive behaviour therapy (group and individual) Medication: Same principles as non-postpartum – all antidepressant medications pass into breastmilk at < 10% of maternal dose; – use of benzodiazepines is NOT an absolute contraindication for breastfeeding with healthy full-term infant

54 Bipolar Disorder Management 1.Prevention: social support, sleep protection, some advise longer stay with rooming out of baby for high risk mothers but evidence limited for this strategy 2.Safety Assessment: mother, baby (+/- other kids) 3.Treatment: based on nature and severity of illness – Psychotherapy: Strongest evidence for Interpersonal Therapy (IPT) where focus is on role transition to parenthood and improving communication abilities and social support – Psychotropic medication: as indicated, consider passage into breastmilk and risk of toxicity – Somatic Therapies

55 Management When to refer (examples)? – Diagnostic clarity – Need for specialized psychotherapy – Failure to respond to first-line antidepressant medication treatment – Postpartum psychosis - a psychiatric emergency Do not leave mother unsupervised Send to emergency department (hospital) for assessment and treatment –Form 1

56 Useful References 1.Hendrick, V and Gitlin, M. Psychotropic Drugs and Women: Fast Facts, Norton and Company, NY, 2004. 2.Payne JL, Palmer JT, Joffe H: A reproductive subtype of depression: Conceptualizing models and moving toward etiology. Harv Rev Psychiatry 17: 72-86,2009 3.Yonkers KA, Wisner KL, Stewart DE, Oberlander TF, Dell DL, Stotland N, Ramin S, Chaudron L, Lockwood C. The management of depression during pregnancy: A report from the American Psychiatric Association and the American College of Obstetricians and Gynecologists. Gen Hosp Psychiatry Sep-Oct;31(5):403-13, 2009 4.Yonkers KA, Vigod S, Ross LE. Diagnosis, Pathophysiology and management of mood disorders in pregnant and postpartum women. Obstet Gynecol. 2011 Apr;117(4):961-77. Review. 5.Cohen LS: Treatment of bipolar disorder during pregnancy. J Clin Psychiatry 68 Suppl 9: 4- 9,2007 6.Einarson A, Boskovic R: Use and safety of antipsychotic drugs during pregnancy. J Psychiatr Pract 15: 183-192,2009 56

57 Questions/Discussion 57


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