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Maternal Mental Health: Impact, Identification, and Intervention Ashley Blackmon Jones, MD Associate Professor of Clinical Psychiatry Adjunct Associate Professor of Clinical Obstetrics and Gynecology April 2019

Objectives Focus: Depression and Anxiety Impact Identification Illnesses Screening Tools Interventions Biopsychosocial Model in Treatment planning Pregnancy Postpartum Challenges and Resources

Perinatal Disorders Prevalence of psychiatric disorders in reproductive age females 2 medical conditions Pregnancy/Postpartum Psychiatric Illness 2 patients Mother Fetus/Baby Family Unit

Pregnancy Up to 20% of pregnant women have anxiety or mood symptoms during pregnancy Depression First trimester 7 % Second trimester 13 % Third trimester 12 %

Perinatal Anxiety Disorders Less attention than depression Late 20 s peak time for anxiety disorders to present in women Perinatal Anxiety: 13-16.5% Perinatal Onset OCD: 18%-40 % OCD 60-80% comorbidity with MDD PTSD Pregnancy: 7.7%-7.9%

Postpartum Disorders Baby Blues 85% Depression 10% PTSD 3.6%-6.3% OCD 11% prevalence 2 weeks postpartum Postpartum Psychosis 1-2/1000

Screening in Pregnancy Clinical Interview Similar techniques as any other chief complaint Information from partner or family DSM 5 Diagnosis/Illnesses Rule Out Other Illnesses or Causes Screening tools EPD, GAD-7, PASS

Edinburgh Postnatal Depression Scale

GAD-7

OASIS

PASS Perinatal Anxiety Screening Scale (PASS) 31 item Broad range of disorders Includes questions specific to perinatal period Identifies: 1. Acute Anxiety & Adjustment 2. General Worry & Specific Fears 3. Trauma, Control, & Perfectionism 4. Social Anxiety

Positive Screen What Next? Assess severity Assess for suicide Diagnostic clarity-rule out other possible disorders Full medical work up Consider all biopsychosocial support & treatment options What does the patient prefer? Consider risks vs benefits of treatment options AND risks vs benefits of no treatment. Schedule close follow up visits Don t forget to keep administering the scales Watch for Response, Remission

Medications in Pregnancy: Depression and Anxiety NO medication for depression or anxiety is FDA approved for use in pregnancy All medication discussion is off label Risks Benefits

Risks and Benefits Risks Medications to mom Medications to fetus/baby Untreated depression or anxiety to mom Untreated depression or anxiety to fetus/baby Benefits Medications to mom Treated depression or anxiety to fetus/baby

Pregnancy and Antidepressants Teratogenesis/Congenital Malformations Miscarriage and Stillbirths Preterm delivery Gestational weight Neonatal Adaptation Syndrome PPHN Long term effects

Congenital Malformations: Meta-Analysis 2013 No increased risk of congenital malformations Statistically significant risk of CV but not clinically significant Population Based Study 2014 No increased risk of CV malformations Concern about paroxetine category D SNRI (2015 Meta-analysis) Venlafaxine 5 Studies 3 cohort prospective studies found no significant association 1 case control hypospadias 1 case control anencephaly, ASD, COA, cleft palate, gastroschisis Duloxetine 4 studies 3 no CM (case reports) 1 clubfoot, kidney agenesis, hydronephrosis (1.8%) was within baseline of general population (prospective) Congenital Malformations: Small absolute risk Data mixed for certain medications, particularly paroxetine Recent Data Reassuring

Miscarriage/Stillbirth SSRI 2013 Meta Analysis No increased risk when comparing untreated illness with SSRI exposure But did compared to control 2013 Meta Analysis No increased risk 2014 Database study raised issue of illness as possible risk Possibly higher with bupropion Venlafaxine: 1-Assocated with risk of SA, dose association with more than 150mg/day 2-small increased risk of SA 3-No higher risk of SA Stillbirths/Neonatal Deaths 2013 study in JAMA Initially showed increase risk with stillbirth and postneonatal death, no increased risk with neonatal death ****BUT**** Showed no increased risk after controlling for: maternal psychiatric illness cigarette smoking advanced maternal age country Miscarriage/Stillbirth Summary: Recent data reassuring. Emphasizes possible association with maternal illness and other factors. Possible small MC risk with bupropion and dose-dependent with venlafaxine.

Preterm Delivery, Birth Weight, APGAR 2013 meta-analysis of 23 studies Significant associations between prenatal antidepressant exposure and gestational age preterm delivery lower birth weight lower APGAR scores 2015 study with SNRI s suggests risk

Neonatal Distress/Adaptation Syndrome ~ 25%-30% of babies exposed in late pregnancy Most common: tremor, restlessness, increased muscle tone, increased crying Relatively benign and short-lived (1-4 days) Do not use term withdrawal Tapering before delivery (3 rd trimester)? No

Persistent Pulmonary Hypertension of the Newborn (PPHN) 1 report: SSRI after 20 wks increased risk of PPHN by six fold Still relatively small Less than 1% in infants exposed to SSRI in utero 3 studies: no association between antidepressant use during pregnancy and PPHN 1 study showed less than 1% risk

Long Term: Development, Behavior, ASD, ADHD Development and Behavior no significant differences in IQ, temperament, behavior, cognition, language reactivity, mood, distractibility, or activity level 1 study showed lower psychomotor scores with SSRI exposure Untreated illness after delivery negative effects on language Depression duration associated with negative effects on IQ Depression associated with behavioral problems ASD and ADHD Conflicting data regarding association of ASD and SSRI exposure 2016 Systematic Review and Meta- Analysis 2, 2017 Retrospective Cohorts No statistical association between SSRI exposure and ASD. 1 study showed significant association between SSRI exposure and healthy controls, but NO significant association when compared to untreated maternal illness.

Untreated Depression/Anxiety Potential Maternal outcomes/associations Operative delivery Obstetrical Complications Substance use Pre-eclampsia Poor prenatal care and nutrition Suicidal behaviors Quality of life Relationship with Partner Potential Neonatal outcomes Preterm delivery Low birth weight NICU admission Decreased breastfeeding initiation Behavioral changes in offspring Suboptimal neurobehavioral scores Cortisol Elevated urinary cortisol/catecholamines after delivery Enhanced stress cortisol response at 12 months Bonding in Postpartum period Impaired immune/stress response Microstructure brain changes

Treatments: Non-Pharmacological Psychotherapy Cognitive Behavioral Therapy Relaxation Techniques Couples Therapy Interpersonal Therapy Mindfulness Yoga

Treatments: Non-Pharmacological Increase support system Limit substances, caffeine, nicotine Education on pregnancy, parenting, mental illness Referrals Social Work, Counseling, Psychotherapy, Vocational Rehabilitation ECT (severe depression and psychosis)

Postpartum Psychiatric Disorders Disorder % of women experience Time Course Symptoms Postpartum Blues Postpartum Depression Postpartum Psychosis 50-85% During first 2 weeks, peak day 4-5 10 % Within 1-3 months typically 1-2/1000 women 2 days to 2 weeks (can be later) Tearfulness Anxiety Irritability Mood Lability Depression Guilt Anxiety Fear of harm to baby Obsessions Restless, Irritable Disorientation Insomnia Delusions Hallucinations Rapid Mood Cycling

Postpartum Psychiatric Disorders Disorder % of women experience Time Course Symptoms Postpartum Blues Postpartum Depression Postpartum Psychosis 50-85% During first 2 weeks, peak day 4-5 10 % Within 1-3 months typically 1-2/1000 women 2 days to 2 weeks (can be later) Tearfulness Anxiety Irritability Mood Lability Depression Guilt Anxiety Fear of harm to baby Obsessions Restless, Irritable Disorientation Insomnia Delusions Hallucinations Rapid Mood Cycling

Postpartum Depression 7-13% prevalence rate * Consequences Child: Less facial expression More fussiness Slowed motor development Ineffective emotional regulation Fear, anxiety, lower self-esteem Insecure attachment behaviors Bonding Behavioral problems Physical (short stature) Family Stress Relationship problems Personal Quality of life Suicide

Postpartum Psychiatric Disorders Disorder % of women experience Time Course Symptoms Postpartum Blues Postpartum Depression Postpartum Psychosis 50-85% During first 2 weeks, peak day 4-5 10 % Within 1-3 months typically Emergency 1-2/1000 women 2 days to 2 weeks (can be later) Tearfulness Anxiety Irritability Mood Lability Depression Guilt Anxiety Fear of harm to baby Obsessions Restless, Irritable Disorientation Risk of infantcide & Insomnia Suicide Delusions Hospitalize!! Hallucinations Rapid Mood Cycling

Other Postpartum Disorders PTSD Exacerbation New Onset OCD peak onset 2 weeks 73% of women already with OCD report worsening postpartum Intrusive Thoughts

Intrusive Thoughts

PBQ Postpartum Bonding Questionnaire 25 Question 1. Impaired Bonding 2. Rejection and Pathological Anger 3. Infant-Focused Anxiety 4. Incipient Abuse

Medications in Breastfeeding Ask your patient if they are breastfeeding Be non-judgmental and have open discussion with patient All medications are secreted in breastmilk There are antidepressants that have been found to be in lower concentration in breastmilk Sertraline, paroxetine Small number of case reports Jitteriness, irritability, excessive crying, sleep disturbance, trouble feeding

Recommendations Clinicians: Threshold for treating mild depression or anxiety with medications is higher. Attempt to limit exposures: Illness (by not treating) Do not taper before delivery Medications (number, switching, dose) Utilize the lowest most effective dose in pregnancy and breastfeeding. Start low if clinically possible (treat patient, not dose) Attempt monotherapy and minimize switching Think through the continuation of treatment (breastfeeding, postpartum) SSRI s have the most reassuring data for depression and anxiety, though would not utilize paroxetine as first line

Recommendations Regularly screen patients for mental wellbeing during pregnancy and postpartum. Always screen for suicide and homicide Individualized Treatment Plans: Biological Psychological Social/Spiritual/Cultural Informed decision made in collaboration with patient (and sometimes family)

Recommendations Evaluate family unit stability and resources Assess and provide information about illness, treatments, cosleeping, sedation Examine your own thoughts, affect, opinions around breastfeeding before advising your patient Know local and national resources

Challenges Access Payer System Referral Sources Reproductive Psychiatry Expertise Stigma and myths about treatment in pregnancy Risk perception Standard accepted guidelines What to do after screening?

Possible Solutions Advocacy Patient Access Provider support Integrated or Collaborative Care Teaching and Training Models Develop Programs: MCPAP for Moms

Resources

References Bryan H. King, MD, MBA 1,2 Assessing Risk of Autism Spectrum Disorder in Children After Antidepressant Use During Pregnancy JAMA Pediatr. 2016;170(2):111-112. doi:10.1001/jamapediatrics.2015.3493. Hosseini, et al. Trait Anxiety in Pregnant Women Predicts Offspring Birth Outcomes. Paediatric and Perinatal Epidemiology, 2009. Brockington, Fraser, and Wilson. The postpartum bonding questionnaire: a validation. Arch Womens Ment Health (2006) 9: 233 242 www.womensmentalhealth.org Furu, et al. Selective serotonin reuptake inhibitors and venlafaxine in early pregnancy and risk of birth defets: population based cohort study and sibling design. British Medical Journal, 2015. Bellantuono, et al. The safety of serotonin-noradrenaline reuptake inhibitors (SNRIs) in pregnancy and breastfeeding: a comprehensive review. Human Psychoharmacology Clin Exp, 2015. Johansen et al. Maternal Use of Selective Serotonin Reuptake Inhibitors and Risk of Miscarriage-Assessing Potential Bias. Paediatric and Perinatal Epidemiology, 2014. Kjaersgaard MIS, Parner ET, Vestergaard M, Sørensen MJ, Olsen J, et al. (2013) Prenatal Antidepressant Exposure and Risk of Spontaneous Abortion A Population-Based Study. PLoS ONE 8(8) Newport, D.J., Fernandez, S.V., Juric, S., Stowe, Z.N. Chapter 64. Psychopharmacology During Pregnancy and Lactation. APA Textbook of Psychopharmacology: Huybrechts, K.F., et al. Antidepressant Use in Pregnancy and the Risk of Cardiac Defects N Engl J Med 370;25; June 2014. Ross LE, et al. Selected Pregnancy and Delivery Outcomes After Exposure to Antidepressant Medication: A Systematic Review and Meta-analysis. JAMA Psychiatry, 2013. Grigoriadis, et al. Impact of Maternal Depression during pregnancy on perinatal outcomes: Systematic Review and Meta Analysis. J Clin Psychiatry; Focus on Women s Mental Health, 2013. Massachusetts Child Psychiatry Access Program www.mcpapformoms.org

References Sujan AC, Rickert ME, Oberg AS, et al. Associations of Maternal Antidepressant Use During the First Trimester of Pregnancy with Preterm Birth, Small for Gestational Age, Autism Spectrum Disorder and Attention-Deficit/Hyperactivity Disorder. JAMA, 2017. Brown, HK, Ray JG, Wilton AS, Lunsky Y, Gomes T, Vigod SN. Association Between Serotonergic Antidepressant Use During Pregnancy and Ustism Spectrum Disorder in Children. JAMA, 2017. Overview by Dr. Meltzer-Brody Grigoriadis, S., et al. Antidepressant Exposure During Pregnancy and Congential Malformations: Is There an Association? A Systematic Review and Meta-Analysis of the Best Evidence. J Clin psychiatry 74:4, Focus on Women s Mental Health, April 2013. Ross and McLean. Anxiety Disorders During Pregnancy and the Postpartum. A Systematic Review. Journal of Clinical Psychiatry, 2006. Stephansson, O., et al. Selective Serotonin Reuptake Inhibitors During Pregnancy and Risk of Stillbirth and Infant Mortality, JAMA 2013. Nulman, et al. Neurodevelopment of Children Following Prenatal Exposure to Venlafaxine, Selective Serotonin Reuptake Inhibitors, or Untreated Maternal Depression. Am J Psychiatry; 169:1165 1174, 2012. Nulman, I., et al. Child Development Following Exposure to Tricyclic Antidepressants or Fluoxetine Throughout Fetal Life: A Prospective, Controlled Study. Am J Psychiatry ; 159:1889 1895, 2002. Seng, et al. Exploring posttraumatic stress disorder symptom profile among pregnant women. J Psychosom Obstet Gynaecol, 2010. Onoye, J.M, et al. Changes in PTSD Symptomatology and Mental Health During Pregnancy and Postpartum. Arch Womens Mental Health, 2013. Grigoriadis, et al. Prenatal exposure to antidepressants and persistent pulmonary hypertension of the newborn: systematic review and meta-analysis, BMJ 2014. Brandes et al. Postpartum Onset Obsessive-Compulsive Disorder: Diagnosis and Management. Arch Womens Ment Health, 2004 Miller ES et al. Obsessive-compulsive Symptoms During the Postpartum Period. A Prospective Cohort. J Reprod Med, 2013 Ulmer-Yaniv et al. Maternal depression alters stress and immune biomarkers in mother and child. Depression and Anxiety, 2018. Dean D, et al. Association of Prenatal Maternal Depression and Anxiety Symptoms with Infant White Matter Microstructure. JAMA Pediatr, August 2018. Presentation given by Erin Murphy-Barzilay, MD and Lee Cohen, MD at 2017 Perinatal Mental Health Conference in Chicago, Il. Andrade, C. The safety of duloxetine during pregnancy and lactation. Clinical and Practical Psychopharmacology, 2014. American Pregnancy.org NIMH Psychiatric News February 2013 Other presentations given with Dr. Stephanie Berg