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Learning Objectives Women s Mental Health Know what to do when a pt c/o PMS Gain knowledge about depression in women Be able to review risks/benefits of antidepressants during pregnancy Learn about post-partum mental health Ellen Haller, M.D. WomenCare Mental Health Program Depression Center at UCSF UCSF Department of Premenstrual Syndrome & Premenstrual Dysphoric Disorder PMS described for centuries & across cultures 30-80% of women have some PMS symptoms during some of their ~400 menstrual cycles More significant PMS symptoms in ~30% PMDD in only 3-8% PMDD DSM dx criteria in syllabus

Daily Symptom Diary Daily Symptom Diary Which of the following interventions is proven to help reduce PMS/PMDD symptoms? 1. Progesterone supplementation 2. The antidepressant, bupropion (Wellbutrin) 3. Calcium supplementation 4. Increasing salt intake Which of the following interventions is proven to help reduce PMS/PMDD symptoms? 1. 2. 3. Calcium supplementation 4.

PMS/PMDD Treatment Initial approach = basic wellness: salt, caffeine, sugar, sodium, alcohol water, fresh fruit, whole grains Stop smoking Exercise Stress management PMS Treatment with Calcium (Thys-Jacobs et al, Am J OB Gyn 1998) Multi-center, randomized, placebo controlled study, N=497 600 mg bid x 3 cycles 55% had >50% improvement in global sxs 36% with placebo 48% reduction in total sxs scores 30% with placebo Calcium relieved both emotional & physical sxs PMDD Treatment Efficacy of SSRIs in PMS Serotonergic antidepressants Continuous dosing Luteal phase dosing AKA Intermittent dosing Brown J et al, Cochran Library, 2009

OCPs for PMDD Not helpful: Progesterone alone & most combo OCPs May make sxs worse Helpful: Yaz Drospirenone 3 mg + ethinyl estradiol 20 mcg Yaz for PMDD Yonkers et al, OB GYN 2005 Multi-site, DB, RCT N=450, all with PMDD, 18-40 yo Daily ratings 24 days on & 4 days off (with inert pill) Yaz for PMDD Yonkers et al, OB GYN 2005 Found signif. difference betw groups Total sx score: 47% in active drug group over 3 tx cycles 38% in PBO group Response (50% in scores) 48% of active drug group 36% of PBO group Drop-outs: 15% vs 4% Most common SE = nausea & intermenstrual bleeding

How common is depression in women? 20-25% of all women will experience at least 1 episode of depression in their lives Boys & girls have equal rates of depression Beginning with puberty, rates for girls Overall, twice as common in women Why is depression more common in women? Changes in adolescence roles and expectations change dramatically Hormonal factors menstrual cycle, pregnancy, postpartum, perimenopause Medical illnesses such as thyroid disease Medications such as BC pills Psychosocial factors I feel miserable Relationships Victimization Low self-esteem Multiple expectations Socialization Poverty Focus on weight, looks 35 yo with 6 mo h/o depressed mood and: -insomnia -low energy -poor concen. -decr appetite -less interest -passive SI -Functioning at work is impaired -Sxs began after parents announced div. -Had 1 prior episode depression

Treatment Plan for I feel miserable Course of Cognitive Behavioral Therapy (CBT) Rx with an SSRI Depression significantly improved One year later... Depression in full remission Pt. married & planning to become pregnant What s the risk of taking antidepressant while pregnant? Depression and Pregnancy Pregnancy NOT protective Course of Depression in Pregnancy Cohen et al, 2006 10-20% of pregnant women dev MDD Risk factors for depression in preg: Prior h/o dep Poor social support Financial & housing problems Marital discord Ambiv about pregnancy Greater # of children N = 201 Recurrence during pregnancy if stayed on meds = 26% Recurrence if d/c meds = 68%

Depression During Pregnancy Poor prenatal care Smoking & substance abuse Suicide Preterm delivery Low birth weight Post-partum depression Treatment of Depression During Pregnancy Psychotherapy proven effective Interpersonal Psychotherapy (IPT) Cognitive Behavioral Therapy (CBT) Antidep Rx--main areas of concern: Miscarriage Congenital organ malformations Adverse effects in newborn Long-term behavioral problems Which is the most true statement about antidepressant Rx in pregnancy? 1. SSRIs are contraindicated 2. SSRIs are completely safe 3. Not enough data exists to help make an educated recommendation 4. An individualized risk-benefit assessment must guide decision-making 5. TCAs are contraindicated Which is the most true statement about antidepressant Rx in pregnancy? 1. 2. 3. 4. An individualized risk-benefit assessment must guide decision-making 5.

Miscarriage TCAs During Pregnancy Possible incr risk for spontaneous abortion Quantitative review (n = 3,567) Rate 12.4% for women who used antidep Rate 8.7% for women not exposed to antidep (Hemels et al, 2005) No congenital malformations Nortriptyline & desipramine preferred Some potential for neonatal w/d sxs & antichol. sxs Jitteriness, tachypnea, tachycardia, irritability, feeding difficulties, diaphoresis Constipation, bladder distension SSRIs During Pregnancy (ACOG, 2008) No incr rate of major or specific cardiac malformations BUT, paroxetine is different Paroxetine (Paxil and Paxil CR) Retrospective study of 3,581 preg women (Louik et al, 2007) risk cardiovascular malform. for paroxetine OR 2.08 10/14 infants had ventricular septal defects Separate study of 4,291 babies exposed to SSRIs found no differences (Hallberg 2005) FDA reclassified as Class D drug

Other antidepressants during pregnancy bupropion, duloxetine, escitalopram, mirtazapine, nefazodone, venlafaxine, and duloxetine Fewer reports; no evidence of congenital malformations Perinatal Effects of SSRIs Multiple sxs reported in 30% of exposed neonates Agitation, jitteriness, sleep disturbance Tremor Rigidity Feeding problems Excessive crying Typically resolve w/in 48 hrs w/o medical intervention Due to either w/drawal or serotonergic hyperstimulation Consider or d/c of antidep. prior to delivery Levinson-Castiel, 2005; ACOG 2008 Child Development After Fetal Exposure Nulman et al, 2002 Prospective study exposed throughout pregnancy TCAs (n=46) Fluoxetine (n=40) Non-depressed Controls on no meds (n=36) Followed children up to 71 months No differences found in: Global IQ Language Behavior Temperament IQ was negatively assoc with duration of depression Deciding to Rx Antidep in Pregnancy ACOG Practice Bulletin, 2008 Need to perform individual risk:benefit analysis Assess severity of anxiety/depression & h/o response to treatment Document other exposures alcohol, cigs, Rx & OTC drugs Document informed consent

Post-partum mental health I just feel so tired 37 yo primip No prior h/o depression Now 7 wks postpartum Sxs: depressed mood fatigue overwhelmed and ashamed anxious about caring for baby; fears mistake appetite insomnia--even when baby asleep Post-partum depression occurs in what percent of women? Post-partum depression occurs in what percent of women? 1. 0-5% 2. 6-10% 3. 11-15% 4. 16-20% 5. 21-25% 1. 2. 3. 11-15% 4. 5.

Spectrum of Postpartum Mood Changes Transient, nonpathologic Postpartum Blues risk for MDD 50% to 70% Serious, disabling Postpartum Depression 2/3 have onset by 6 wks postpartum 10% Medical emergency Postpartum Psychosis 70% are affective (bipolar, MDD) 0.01% PPD Risk Factors Unsupportive partner/rel. conflict/stress FH depression or bipolar d/o h/o depression h/o PMDD Prior h/o PPD (50% risk) Depression during current pregnancy Post-partum blues Pearlstein 2009, Cohen 2010 Cohen LS. Depress Anxiety. 1998:1:18-26. Therefore, During prenatal care, screen for past h/o mood d/o in both pt & family At 6 wk post-partum check, screen for current sxs Edinburgh Postnatal Depression Scale 10 item questionnaire Score of >12 indicates probable postpartum depression

PPD Management Recommendations Reassurance & support Postpartum Support International www.postpartum.net Psychotherapy Interpersonal Psychotherapy (IPT) Cognitive Behavioral Therapy (CBT) Pharmacotherapy for PPD Payne JL, 2007; ACOG Practice Bulletin, Apr 2008 Relatively few studies have evaluated antidep specifically for PPD No study compares psychotx to pharmacotx Fluoxetine shown better than PBO Double-blind trial of sertraline vs NTP showed both effective and no difference betw them Medications BOTTOM LINE: Assume Rx for PPD has same response as tx for other depression Cohen, 2010 Psychotropic Drugs During Lactation Di Scalea TL, Wisner KL, 2009 All are excreted in human breast milk As a class, have more data in breastfeeding than any other Sertraline, paroxetine, NTP & IMI are most evidence-based meds Summary PMS/PMDD are real d/o Prospective charting useful tool Mgmt = basic wellness calcium SSRIs intermittently or Yaz SSRIs continuously Depression is more common in women For pregnant pts, complete an individualized risk-benefit analysis 3 classes of postpartum mood disorders

Resources Office of Women s Health www.4woman.gov/owh/ American Psychiatric Association patient info www.healthyminds.org Center for Women s Mental Health at Mass Gen l www.womensmentalhealth.org Chart on meds in pregnancy www.hfs.illinois.gov/assets/062111mch.pdf Info on meds in breastfeeding http://toxnet.nlm.nih.gov