Promoting Maternal During and After 2 3 4 5 6 Perinatal is the most common complication of pregnancy

http://www.acog.org/Womens-Health/Depression-and-Postpartum-Depression Perinatal depression is twice as common as gestational diabetes

Depression 10-15 in 100

Diabetes 3- 7 in 100

Gavin et al. Ob Gyn 2005, Vesga-Lopez et al. Arch Gen 2006. ACOG Practice Bulletin 2013. Perinatal depression affects mom, child & family

Poor health care Preeclampsia Maternal suicide

Low birth weight Preterm delivery Cognitive delays Behavioral problems

Bodnar et al. J Clin Psych 2009. Cripe et al. Pedi &Perinatal Epid 2011. Forman et al. Dev & psych 2007 Two-thirds of perinatal depression begins before birth

Pregnancy 33%

Before pregnancy Postpartum 40% 27%

10 Wisner et al. JAMA Psychiatry 2013 Perinatal depression is under-diagnosed and under-treated

Treated Women

Untreated women

11 Byatt N, et al. Obstetrics and Gynecology. 2015. 855-Mom- Care Education MCPAP Coordination Telephone Consultation

Obstetric Family Psychiatric Primary care Pediatric providers/ Medicine providers providers providers Midwives 1-855-Mom-MCPAP

Telephone Consultation

Obtain and document patient consent before sharing PHI with MCPAP for Moms

14 1-855-Mom-MCPAP

Telephone Consultation

Obtain and document patient consent before sharing PHI with MCPAP for Moms

15 www.mcpapformoms.org Management of perinatal psychiatric disorders

Pregnancy Guiding principles Depression & Anxiety Bipolar & Postpartum Think pregnancy for ALL reproductive aged women

Half of are unplanned

Finer & Zolna Contraception 2011. Document preconception discussion

Document contraception

Discuss risks of teratogenic medication Avoid valproic acid

Note interaction between hormonal contraception and mood stabilizers - Pill can decrease lamotrigine levels - Oxcarbazepine can decrease BCP efficacy Risk depends on stage of pregnancy The U.S. FDA pregnancy risk categorization is limited Not consider risks of maternal illness Not consider Unclear benefits of categories medication

Does NOT inform decision making No choice is completely free of risk

Need to balance and discuss the risks and benefits of medication treatment and risks of untreated mental illness Management of perinatal psychiatric disorders

Pregnancy Guiding Principles Depression & Anxiety Bipolar & Psychosis Postpartum High risk of relapse during pregnancy in woman discontinuing antidepressants preconception

Continue

Discontinue

*If tapering medication prior to conception, continue to follow women during pregnancy.

Cohen et al. JAMA 2006 . Yonkers et al, Epidemiology 2011. Past depression is the # 1 risk factor for perinatal depression

Reproductive Related RF General RF • Personal history of • Younger age • High • Childhood trauma • Family history of • postpartum depression • Psychosocial • Domestic violence • History of mood • Chronic medical condition changes related to hormonal changes • Race

Melville et al OBGYN 2010 ; Meltzer-Brody et al, Arch Women MH2013 Education about various treatment and support options is imperative Case of Ms. Y No decision is risk free

Vs.

SSRIs are among the best studied class of medications in pregnancy

Byatt et al. Acta Psych Scand 2013. Same prescribing principles for preconception, pregnancy and breastfeeding

Use what has previously worked (considering available reproductive safety information) Use lowest EFFECTIVE dose

Minimize switching

Monotherapy preferable Be aware of need to adjust dose with advancing pregnancy Discourage stopping SSRIs prior to delivery Most data does not support increased risk of birth defects

Data is inconsistent, paroxetine has been most controversial

Byatt et al. Acta Psych Scand 2013. Possible transient neonatal symptoms with exposure to antidepressants

Transient and self-limited syndrome that may occur in up to 30% of neonates Data does not support taper in third trimester

Moses-Kolko et al JAMA 2005, Warburton et al. Acta Psychiatr Scand 2010. Absolute risk of persistent pulmonary hypertension (PPHN) appears small

Baseline rate of 1-2 per 1000 births, may increase to 3-4 in 1000 births

Chambers et al. NEJM 2006, Kallen et al. Pharmacoepidemiol Drug Saf 2008, Andrade et al. Pharm Drug Saf 2009. Possible association with preterm labor & low birth weight

Depression also a risk factor for preterm labor & low birth weight

Huybrechts, N Engl J Med. 2014; Ross JAMA Psychiatry 2013 Limited studies do not suggest long-term neurobehavioral effects on children

Postpartum depression is associated with negative neurobehavioral effects on children

Nulman et al. AJP 2012, Croen et al. AGP 2011, Rai et al BMJ 2013. When possible, slowly taper benzodiazepines, with goal to be on lowest possible dose Possible risks Cleft lip/palate Preterm birth Low birth weight Neonatal withdrawal syndrome/rare risk of floppy infant

Guidelines Monotherapy preferable to polypharmacy, so optimize SSRI first Fewer/no active metabolites (lorazepam) may be safer Try to avoid longer-acting benzos, e.g. diazepam 35 Management of perinatal psychiatric disorders

Preconception Pregnancy Depression & Anxiety Bipolar & Psychosis Breastfeeding Imperative to address

Bipolar Disorder 23% Unipolar Depression Other 7% 69%

Wisner et al. JAMA Psychiatry 2013 During pregnancy medication discontinuation increase risk for recurrence of bipolar disorder

120 100% 100

80 62% 60

40

20

0 Abrupt Discontinuation > 14 day taper

Yonkers et al. AJP 2004 High risk of relapse for bipolar disorder after medication discontinuation postpartum

Viguera et al. AJP 2000 Bipolar Disorder in pregnancy is associated with negative outcomes

Pregnancy does not protect against mood episodes

Bipolar (like depression) is associated with - low birth weight, - preterm <37wks - small for gestational age

Increased rate of C-section

Mood elevation can lead to behaviors with known perinatal risk (eg Substance use, high risk driving, hypersexuality) Mei-Dan et al, AM J OB Gyn 2015, Boden Et al, BMJ 2012 Bipolar disorder increases risk of

1-2/1000 women >70% bipolar disorder 24 hrs – 3 weeks postpartum Mood symptoms, psychotic symptoms & disorientation R/o medical causes of Psychiatric emergency 4% risk of infanticide with postpartum psychosis

41 Wesseloo et al AJP 2016, Manic Depression Illness, Goodwin and Jamison, 2007 Preventing decompensation among women with bipolar disorder is critical

Prophylaxis with mood stabilizer A birth plan Close monitoring Collaboration with newborn medicine Plan for infant feeding Support adequate sleep Limit stress Support maternal-infant bonding

wesselloo 2015 Risk of harm to baby when mother has thoughts of harming baby

OCD/anxiety/depression Postpartum Psychosis

• Good insight • Poor insight • Thoughts are intrusive • Psychotic symptoms and scary • Delusional beliefs or • No psychotic symptoms distorted reality present • Thoughts cause anxiety

Low risk High risk

43 Many mood stabilizers can be used during pregnancy

Lower Emerging Avoid risk reassuring data (if possible)

Typical Atypical Carbamazepine/ Antipsychotics Antipsychotics Oxcarbamazepine

Lamotrigine Lithium Valproic Acid Lithium use in pregnancy as been associated with risks to mother and baby

Preterm labor Large for gestational age Polyhydramnios Cardiac defects (Epstein’s anomaly) Polyuria/polydipsia Neural tube defects (possible small) Lithium toxicity Neonatal adaption/floppy baby Long-term developmental issues?

Wesselloo BJP, 2017 Pharmacokinetics of lithium (and most other meds) changes during pregnancy

Blood flow Respiratory ∆s ∆s

↑ cardiac ↓ albumin output

↑ plasma ∆ in drug ↑ GFR volume conc Monitor lithium levels closely during the perinatal period

Preconception 1st 2nd 3rd Birth Postpartum

Obtain Check level q3 weeks until Continue Li at onset of baseline week 34 labor level Check level weekly after week 34 ↓ dose to preconception level within 2-3 weeks Likely ↑ dose Check levels 1-2x/w after Twice daily dosing delivery *Maintain a narrow therapeutic index of 0.6-1.2mEq/L

Wesseloo et al. Br J Psych. 2017. Additional monitoring is necessary when using lithium during pregnancy

Patient needs high-risk Ob Fetal echocardiogram at 16-18 wks GA Monitor:

Infants’ lithium serum levels, TSH, renal function Monitor for interactions: Increase Li levels

NSAIDS, diuretics (HCTZ), ARBs ACE-I Decrease Li levels

Caffeine and theophylline

Galbally et al, Aus NZ J Psychiatry 2010, Wesseloo et al. Br J Psych. 2017 Use antipsychotics that work, while taking into account relative risks of medications

No single malformation consistently reported (some data suggests may  ASDs/VSDs) Preterm labor Low and high birth weight Increased risk of postnatal adaptation symptoms Increase risk of NICU stays

Coughlin et al, OB GYN 2015; Tosato et al J Clin Psyc 2017, Ennis et al, Basic Clin Pharmacol Toxicol. 2015; Huybrechts et al, JAMA Pscy 2016; Cohen et al AJP2016, Vigod et al, BMJ 2015 Second generation antipsychotics have an increasing role in treatment

FGA SGA Antipsychotics Antipsychotics

Small risk of transient Gestational diabetes & abnormal muscle movement obesity

Long-term data reassuring Limited data to 12 months though limited 2/2 indication somewhat reassuring

Vigood et al, BMJ 2015, Cohen et al, AJP, 2015, Huybrechts et al, JAMA Psychiatry 2016. Minimize stimulant use and optimize behavioral interventions during pregnancy Premature birth

Smaller size

Neonatal withdrawal symptoms

Postpartum hemorrhage Maternal hypertension Limited, but reassuring data on first trimester use

Limited, but reassuring long-term developmental data

Small amounts passed through to breastmilk

Freeman AJP, 2014 ; Huybrechts JAMA Psyc, 2017 Management of perinatal psychiatric disorders

Pregnancy Depression & Anxiety Bipolar & Psychosis

Postpartum Breastfeeding generally should not preclude treatment with antidepressants

SSRIs and most psychotropics are considered a reasonable option during breastfeeding Sertraline, paroxetine, nortriptyline & imipramine have lowest passage into milk of the antidepressants

Di Scalea & Wisner, Clin Ob & Gyn, 2009 Antipsychotic use should not preclude the possibility of breastfeeding

Quetiapine, olanzapine, risperidone < Typicals

*Use what has worked in the past, considering reproductive data. Breastfeeding

Safer Higher Risk

Antidepressants Carbamazepine Lithium Antipsychotics Valproic Acid Lamotrigine Among mood stabilizers, lithium requires most caution during breastfeeding

Medication AAP Carbamazepine Usually compatible with breastfeeding Valproic acid Usually compatible with breastfeeding Lamotrigine Unknown, but may be of concern Lithium Significant side effects, should be used with caution Infant monitoring is recommended during lactation for certain medications

Drug Infant Monitoring

Carbamazepine CBZ level, CBC, liver enzymes Valproic acid VPA level (free and total), liver enzymes, platelets Lamotrigine Rash, liver enzymes Lithium BUN, CRE, TSH, CBC, li

Typical Stiffness, CPK antipsychotics Atypical Weight, blood sugar antipsychotics In summary, psychiatric disorders affect mom, baby and family

Mom Fetus/Pregnancy Child/Family

• Suffering • Preterm birth • ↑ risk of • Poor self- • LBW depression care • HTN & • Child Preeclampsia • Suicide development • • Siblings

No decision is risk-free MCPAP for Moms aims to promote maternal and child health by building the capacity of front line providers to address perinatal mental illness Resources

• MCPAP for Moms – Mcpapformoms.org • MGH Center for Women’s Mental Health – Womensmentalhealth.org • Reprotox – Reprotox.org • Postpartum Support International – Postpartum.net • Lactmed – toxnet.nlm.nih.gov/newtoxnet/lactmed.htm Acknowledgements MCPAP for Moms is funded by the Massachusetts Department of Mental Health MCPAP for Moms Consulting Leadership Psychiatrists

Nancy Byatt, DO, MS, MBA, FAPM Kara Brown, MD Brigham and Women’s Hospital / Medical Director, MCPAP for Moms Harvard Medical School UMass Memorial Medical Center / UMass Medical School Wendy Marsh, MD, MSc Leena Mittal, MD UMass Memorial Medical Center / Assoc. Medical Director, MCPAP for UMass Medical School Moms Brigham and Women’s Hospital / Harvard Medical School Valerie Sharpe, MD Baystate Medical Center

64 Please contact us www.mcpapformoms.org Call 855-Mom-MCPAP (855-666-6272)

Thank you!