Robin C. Kopelman, M.D., M.P.H. Clinical Assistant Professor, University of Iowa

1. Mental Health and Contraception Robin C. Kopelman, M.D., M.P.H. Clinical Assistant Professor, University of Iowa Department of Psychiatry Co-Director, Women’s Wellness and Counseling Service Iowa Depression and Clinical Research Center September 17, 2013

2. Overview • Epidemiology of mood disorders in women • Reproductive hormones and mood in women • Mood effects of hormone-based contraception • Mood symptoms and contraceptive use • Contraception and preconception counseling

3. Major Depressive Episode: Diagnostic Criteria • 5 of 9 symptoms, including 1 or 3 (SIGECAPS) • 1 depressed mood • 2 thoughts of death, Suicidal ideation • 3 anhedonia or diminished Interest • 4 worthless or Guilty • 5 fatigue, loss of Energy • 6 poor Concentration, indecisiveness • 7 change in Appetite • 8 Psychomotor retardation or agitation • 9 change in Sleep (insomnia or hypersomnia)

4. Depression: A “women’s issue” Overall rates: 12% per year, 20% lifetime Compared to men: 2 – 3 times more common Difference starts in adolescence

5. Depression Across the Female Reproductive Cycle Depression during pregnancy Depression associated with infertility, miscarriage, or perinatal loss Menarche Pregnancy Menopause Premenstrual depression/anxiety Depression/anxiety during the perimenopausal period Depression during the postpartum period CONTRACEPTION

7. Not just hormones…

8. Reproductive hormones are neuroactive • Progesterone and metabolites • GABA • Estrogen and progesterone • MAO • Opioid, serotonergic, cholinergic NTs • Not simple relationship to mood • U shaped dose-response • Fluctuations, not absolute levels

9. What do we see clinically? • Premenstrual Dysphoric Disorder • Depressive symptoms confined to luteal phase • 3 – 8 % of women of reproductive age • Etiology • Decreased luteal phase serotonin activity related to hormone shifts (progesterone) PMS ≠ PMDD

10. Antenatal Depression • 10 – 20% of women during pregnancy • Select group - role for hormones O'Hara, 1986; O'Hara & Swain, 1986; Hobfoll et al., 1995; Seguin et al., 1999

11. Untreated Antenatal Depression • Inadequate prenatal care • Low birthweight, preterm delivery, spontaneous AB, bleeding, preeclampsia/gestational hypertension, fetal death • Behavior issues in neonate • Developmental effects in children • Increased use of alcohol, drugs, and cigarettes Bonari et al 2004;Kelly et al., 1999; Kelly et al., 2002;Deave et al., 2008

12. Postpartum Blues Common (70 – 80% of women) Linked to hormone shifts 10 days to 2 weeks Peaking at 5 days Associated factors PMDD Depression

13. Postpartum Depression (PPD) 10-20% of Childbearing Women

14. Select PPD Risk Factors Family history 4 – 8 weeks postpartum History of PMDD Implication: hormone shifts play a role

15. Untreated PPD Inconsistent birth control use* Less likely to engage in healthy parenting practices Negative impact on Family Developmental, behavioral, and emotional problems in children Personal suffering of the mother Suicide – a leading cause of maternal death

16. Why do women not use contraception? • Affective symptoms cited as a major reason for contraceptive discontinuation • Historically change in mood “one of the most common reasons” • Study of 79 women – 47% discontinued oral contraceptives within 6 months, 1/3 due to mood changes Oinonen & Mazmanian 2002; Sanders et al. 2001

17. Are mood symptoms a reason to avoid hormonal contraception? • Bottom line: • Results conflicting • Randomized controlled trials on mood effects limited • Mood effect profile may be largely favorable for most women

18. Tori • 27 yo female seen in gyn for painful menses, contraception • Has a history of depression • Currently without mood symptoms • Reports that oral contraceptives make mood symptoms worse and bouts more frequent • “What’s my best option?”

19. Depot medroxyprogesterone acetate • Label warns against use in pts w/ depr hx • 1.5% of 4200 users reported depression, 0.5% d/c’d use because of depr • 16,000 women, 5.4% users vs. 2.3% non-users had mood disorders Rapkin & Sonalkar 2011; Meirik et al. 2001

20. Depot medroxyprogesterone acetate • Studies limited and conflicting • 393 women, 56% d/c’d by 1 year, no increase in depr among cont or d/cers • 63 adolesc (dmpa & controls) – no depr • Role of choice - profile of depot users Rapkin & Sonalkar 2011;Gupta et al. 2001

21. Levonorgestrel • 910 women with LNG implant – 93 drop-outs had higher depr scores, continuers - no increase depression scores at 6 months • Oral LNG = 2 studies, used in combo with EE, no evidence of mood sx • Intrauterine • 3100 women, 212 IU users, no assoc with scores or depr dx • Lower serum level • Maybe good option Westhoff 1998;O’Connell et al 2007;Rapkin & Sonalkar 2011; Toffol 2011

22. Lisa • 36 yo woman, recently hospitalized for anxiety and new episode severe depression, now partially remitted • No history of premenstrual mood symptoms • Considering pregnancy, but not for a few months • “Would using hormonal contraception make my depression worse?”

23. Some data suggest - maybe… • Individual characteristics may play a role • History of depression • Possible premenstrual worsening • History of premenstrual mood symptoms • History of perinatal depression • History of dysmenorrhea • Psychological distress level Oinonen & Mazmanian 2002

24. Oral contraceptives – Evidence for no association • 20,000 women no differences in depressive symptoms users vs. non-users • 3100 women, 181 users, no association with mood symptoms • 151 women, combo/progestin-only/placebo, no between group differences • 76 women, OCP/Placebo, no difference between groups Duke et al. 2007; Toffol et al 2011;Graham et al. 1995;O’Connell 2007

25. Oral contraceptives – evidence for mood benefits • Adolescent girls, placebo vs. OC, depression scores improved • Combo (estr/prog) may improve mood in women with MDD • 1238 women - combo vs. progestin-only vs. none • Combo had lower depression severity • Attributed to ethinyl estradiol O'Connell et al. 2007;Young et al. 2007

26. Erin • 20 yo woman, followed for depression in pregnancy. Now 1 week postpartum. • Mild depressive symptoms. • Does not want to use intrauterine, injectable, or barrier methods. • “Will mini-pill make my depression worse?”

27. Oral contraceptives – Composition • Higher progestin more mood symptoms • Data mixed, but overall studies of progestin-only or higher progestin = greater # and severity depression symptoms • Lower progestin/estrogen ratio may be better

28. Postpartum depression & progestin-only contraception • Long-acting norethistherone enanthate (progestogen only, non-US) • Increased depressive symptoms compared to placebo 6 wks postpartum • No difference at 12 wks • Caution warranted?

29. Angie • History of premenstrual mood symptoms, dysmenorrhea • Referred to gyn for symptom management • Reported worsening of mood with OCPs, self-harm ideation escalating • Charting data indicated an independent major depressive episode • “What should we do next?”

30. Premenstrual Dysphoric Disorder Treatment • SSRIs • Dosing • Continuous • Luteal • Depression - both • Hormonal treatment • GNRH agonists, SubQ or transdermal estrogen • Oral Contraceptives (Yaz) • Drosperinone/Ethinyl Estradiol vs. placebo • Contraception Considerations • May be at increased risk for mood sx fluoxetine 20 mg fluoxetine 40 mg Follicular Luteal

31. Depression & use of contraception • “Survivor” effects • Psychological symptoms predict: • contraceptive nonuse • use of less effective methods • Depression impacts perceptions of provider communication • Limits self-efficacy Barnet et al. 2008; Carvajal et al 2012;Hall et. al 2013

32. Perinatal depression & use of contraception • Perinatal depression may affect: • Contraception use • Birth spacing • Adolescents and women with low-education levels may be particularly vulnerable Patchen & Lanzy 2013; Faisal-Cury et al 2013;Barnet et al. 2008; Bennett et al. 2005

33. Counseling our patients • Acknowledge hormones play a role in mood symptoms • Most women will not develop mood symptoms related to contraception

34. Counseling women with depression • Many reasons to avoid unanticipated pregnancy • Depression impacts pregnancy intervals and outcomes, child outcomes • Risks of contraceptives for women with depression, as well as benefits, may direct to specific options

35. Depression affects: • Health behaviors, like contraception use • Choice of contraception • Perceptions of provider communication • Screen for and treat depression in women

36. Other common disorders • Schizophrenia • Estrogen may be beneficial • Bipolar disorder • As many as 40% not using contraception • Perinatal period = high risk – relapse, psychosis • Several BPAD treatments -- known teratogens • Adherence an important issue

37. What if we need help?Clinical Resource • University of Iowa Women’s Wellness and Counseling Service – UIHC, Iowa River Landing

38. Referrals to the WWC • Perinatal and reproductive psychiatry referrals • Phone 319-335-2464 http://www.uihealthcare.org/womenswellness/

39. Consultation and Support Resource • Iowa Perinatal Mental Health Consultation Service

40. Patient & Provider Resource

41. Summary • Hormones influence mood • Contributor to common disorder in women • Guiding data is limited • Depression influences contraceptive choices and related behaviors • Mood symptoms should be always be evaluated and treated • Resources available