The Use of Psychotropic Medications in Pregnancy and the Postpartum

1. The Use of Psychotropic Medications in Pregnancy and the Postpartum Stephanie Berg, MD Medical Director The Women’s Emotional Health Center At Midlands Psychiatry 125 Alpine Circle Columbia, SC 29223 September 29, 2010

2. Disclaimer • I have nothing to disclose • All discussion of medications is off label as no medications are FDA approved in pregnancy

3. Objectives • Introduction • Antidepressant medications • Pregnancy • Breastfeeding • Mood stabilizer medications • Antipsychotic medications • Antianxiety medications

4. The Women’s Emotional Health Centerat Midlands Psychiatric Service, LLC125 Alpine CircleColumbia, South Carolina29223(803) 779 - 3548

5. Who we are • Stephanie Berg, MD • Psychiatrist • Primary focus is psychiatric medication management and diagnosis of mental health difficulties in women

6. Particular interests • Mood disorders in pregnancy • Mood disorders in the postpartum period • Psychiatric aspects of chronic pelvic pain • Eating disorders • Mood changes with menopause • Mood changes with premenstrual disorders • Mood disorders in victims of interpersonal violence

7. Who we are • Kelly Helms, LISW-CP • Clinical Social Worker • Primary focus is EMDR as well as individual and family therapy for women, infants, and children

8. Particular Interests • Trauma recovery therapy • EMDR (Eye Movement Desensitization and Reprocessing) • For women with history of • Assault • Post-traumatic stress disorder • Anxiety disorder • Abuse history • Perinatal mood disorders • Individual and couple counseling for difficulties with intimacy

9. Particular Interests • Parental counseling of families planning for adoption • Parenting skills in the mother of newborns through toddler age children • Therapy for women struggling with infertility and pregnancy loss

10. Perinatal Psychiatric Disorders • Pregnancy Depression • Postpartum Blues • Postpartum Depression • Postpartum Psychosis • Postpartum Obsessive-Compulsive Disorder • Exacerbation of other illness

11. Antidepressant medications • SSRIs • Fluoxetine (Prozac) • Sertraline (Zoloft) • Paroxetine (Paxil) • Fluvoxamine (Luvox) • Citalopram (Celexa) • Escitalopram (Lexapro) • SNRIs • Venlafaxine (Effexor) • Duloxetine (Cymbalta) • Desvenlafaxine (Pristiq)

12. Antidepressant medications • Other • Wellbutrin (Bupropion) • Norepinephrine and dopamine • Trazodone • Mirtazapine (Remeron) • Tricyclic Antidepressants • Amitriptyline (Elavil) • Nortriptyline (Pamelor) • Imipramine (Tofranil) • Clomipramine (Anafranil) • MAOIs • Phenylzine (Nardil) • Tranylcypromine (Parnate)

13. Perinatal mood disorder treatment scenarios

14. Treating MDD in Pregnancy: The Ideal Situation • Ms. J has a long history of recurrent depression. She is currently stable on sertraline (Zoloft). She would like to become pregnant. What should she do?

15. Versus • Ms. J has had a difficult time becoming pregnant. She is not taking psychiatric medications. Two months after finding out she is pregnant, she notices she feels down and is unsure if she evens wants to continue the pregnancy. What should she do?

16. Versus • Ms. J has a long history of depression and just found out she is pregnant. She is currently taking fluoxetine (Prozac). What should she do?

17. Major Depressive Episode • At least 2 weeks • Sad • Interest • Guilt • Energy • Concentration • Appetite • Feeling restless or slowed • Sleep • Suicidality

18. Depression in pregnancy is common • Up to 30% in low-income populations

19. Detection of Perinatal Depression • Edinburgh Postnatal Depression Scale (EPDS) • Can be used during pregnancy and postpartum • 10-item, self-administered • Easy to score • Score of at least 10-13 indicates depression • Validated in at least 12 languages

20. EPDS

21. Depression in Pregnancy • Risks of untreated depression • Preeclampsia • Placenta abnormalities • Low birth weight • Preterm labor • Developmental delay

22. Depression in Pregnancy • Risks of untreated depression • Poor follow up with OB appointments • Malnutrition, less likely to take folate • More likely to smoke, use alcohol, or other substances • Greater likelihood to develop post partum depression Bonari et al (2004) Can Fam Physician 49;11: 726-735.

23. Postpartum Depression

24. Depression in pregnancy goes untreated • Less than 1/3 of women receive treatment for depression during pregnancy • Who does get treatment? • History of depression • History of psychiatric treatment • Depression severity Flynn et al. 2006

25. What happens to the untreated? Cohen et al. 2006 • High relapse risk • Looked at 201 early pregnant euthymic women on antidepressants (AD) • N = 82 maintained AD • Relapse rate = 26% (n = 21) • N = 65 discontinued AD • Relapse rate = 68% (n = 44) • 90% of relapses occurred by 2nd trimester

26. Depression in Pregnancy • Li et al – 2008 Human Reproduction • 791 women interviewed in early pregnancy • Women with depression had twice the risk of preterm delivery • Related to • Low educational level • History of fertility difficulties • Obesity • Stressful life events • Antidepressants did not contribute to preterm labor

27. Why? • Stress hormones? • HPA axis hyperactivity • Increased placental release of CRH • Prenatal cortisol elevations • Catecholamines • ACTH, cytokines • Altered excretion of vasoactive hormones • Altered neuroendocrine transmitters

28. Medication Choice An individual decision that’s made on a case by case basis!

29. Medication choices • Pre-conception taper • Stop medications entirely • Stop and restart if symptoms • Stop and restart after 1st trimester • Continue through pregnancy • Decrease dose • Reduce or discontinue in late pregnancy • Transition to psychotherapy

30. General Guidelines • Document Document Document • “I have explained the risks, benefits, and alternatives of psychiatric medications in pregnancy. Ms. X (and her partner) have given consent.”

31. General guidelines • Treat a woman as if she could become pregnant at any time… • Up to 80% of pregnancies are unanticipated • Document use of birth control • Encourage use of folic acid and multivitamin

32. FDA labels • Patients read them • They will change • They will be changing • Standard information on background rates • Fetal risk data • Clinical considerations • Registry information

33. FDA Classifications • Most psychotropics are C • None are A • No antidepressants are FDA approved for pregnancy • No drug is “safe” • No good randomized, placebo-controlled studies • Most studies are retrospective, case reports, and registry data

34. Treating Depression in Pregnancy • Think Sertraline (Zoloft)

35. FDA categories of Antidepressants in Pregnancy as of 9/24/10

36. Pregnancy factors that may increase medication concentrations • Reduced gastrointestinal motility • Absorption changes for some medications • Reduced fecal elimination • Serum proteins lower • May result in higher ‘free’ drug concentrations

37. Pregnancy factors that may decrease medication concentration • Total blood volume increases 30 – 40% • 2nd and 3rd trimesters extravascular volume increases • Results in lower plasma levels of meds • Increased kidney plasma flow 30% • GFR increased by 50% • Renal excreted drugs have faster elimination

38. Pregnancy factors that may decrease medication concentration • Nausea and vomiting • Reduced absorption • Increased liver metabolism • May result in increased elimination of certain medications

39. Decrease in blood levels • Sit et al 2008 • N = 11 • Citalopram, escitalopram, sertraline • Blood level decreases at 20 weeks • Increases after delivery • Normalizes by 12 weeks after delivery

40. Prepregnancy Conception 20 weeks Delivery Postpartum Antidepressant Blood Levels and Pregnancy Adapted from Sit et al 2008

41. What should we be concerned about? • Organ malformation (teratogenicity) • Miscarriage is worst outcome of this • Neonatal Adaptation • Physical and behavioral symptoms noted shortly after birth • Related to drug use near time of birth • Limited duration • Long term behavioral abnormalities

42. Medication Background • Incidence of major birth defects in US is 2 to 4% • 65 – 70% of unknown cause • 2 – 4% medication related • Period of maximum vulnerability for birth defects of the nervous system is 14 – 35 days post conception

43. Medication Background • Women usually find out when already 5-7 weeks gestation • Therefore, may want to keep same medication if it’s working

44. Risk of miscarriage • Increased slightly with SSRIs • 1.45 relative risk of miscarriage • Within normal population rates • Bupropion (Chun-Fai-Chen 2005) • N = 136 • Higher rate of spontaneous abortions • 15.4 % vs. 6.7 % • 12.4 % other antidepressants

45. Antidepressants During Pregnancy • SSRI complications • Congenital anomalies • Persistent Pulmonary Hypertension of the Newborn • Neonatal adaptation syndrome

46. SSRIs and NEJM – article #1 • Alwan et al, 2007 • N = 9622 with major birth defects • N = 4062 without birth defects • No overall congenital heart defects • As a group, increased risk of • Anencephaly (OR 2.4) • Baseline rate 20:100,000 • Craniosynostosis (OR 2.5) • Baseline rate 5:10,000 • Omphalocele (OR 2.8) • Baseline rate 1:10,000

47. SSRIs and NEJM – article #2 • Louik et al, 2007 • N = 9849 infants with birth defects • N = 5860 infants without birth defects • No overall birth defects for SSRIs as a group • Sertraline • omphalocele (OR 5.7) • Septal defects (OR 2.0) • Paroxetine • Right ventricular outflow tract obstruction defects (OR 3.3)

48. Pedersen et al 2009 BMJ • n = 493,113 • SSRIs overall increase risk of septal defects (OR 1.99) • Sertraline 3.25 • Citalopram 2.52 • Fluoxetine 1.34 • Multiple SSRIs 4.70 • Risk increases 0.5% to 0.9%

49. Paroxetine • Has FDA warning against using in first trimester due to increased risk of cardiac defects

50. Paroxetine • Berard 2007 • Looked at paroxetine vs. other ADs • 1403 women • 101 with major malformations • 24 of these were cardiac • Paroxetine OR = 1.38 vs. other 0.89 • Not significant • However OR = 2.25 when paroxetine dose > 25mg daily Berard 2007