Mental Health and Womens Health Ellen Haller, M.D. Professor of - PDF document

Disclosure information I have nothing to disclose. Mental Health and Women’s Health Ellen Haller, M.D. Professor of Clinical Psychiatry UCSF Department of Psychiatry UCSF Dept. of Psychiatry Learning Objectives • Know what to do when a pt c/o PMS/PMDD • Review risks/benefits of antidep during preg • Learn about post-partum mental health UCSF Dept. of UCSF Dept. of Psychiatry Psychiatry

Premenstrual Dysphoric Disorder Premenstrual Syndrome (PMDD) Braverman 2007 Cunningham J, 2009; Di Giulio, Reissing 2006 • PMS described for centuries & • 3-8% across cultures; term 1 st used in • Starts in 20s; worsens over time 1950s • PMDD dx criteria in syllabus • Most women have some PMS – Is now formal dx in DSM-5 symptoms during some of their • For up to 90%, PMDD not dx’d ~400 menstrual cycles • For ~40% of pts reporting PMDD, correct dx • More significant PMS symptoms in = premenstrual exacerbation of other d/o ~30% • Need to r/o other psych d/o and hypothy, UCSF Dept. of UCSF Dept. of then prospectively track sxs Psychiatry Psychiatry Symptoms 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 Symptoms 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 Irritable 0 0 0 2 2 3 3 3 3 2 1 0 0 0 0 Depressed 0 0 0 1 2 2 3 3 3 2 1 0 0 0 0 Fatigued 0 0 0 1 1 2 2 2 3 3 2 1 0 0 0 Days of period x x x x x Days of period Symptoms 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 Symptoms 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 Irritable 0 0 0 0 0 0 1 0 0 0 0 0 0 0 0 Depressed 0 1 0 0 0 0 0 0 0 0 0 0 0 0 0 Fatigued 0 0 0 0 0 0 0 0 0 0 0 1 0 0 0 Days of period Days of period Month _ ____________ Month __ April, 2013_____________ Grade each symptom daily: Grade each symptom daily: None = 0 None = 0 Mild = 1 UCSF Dept. of UCSF Dept. of Moderate = 2 Mild = 1 Psychiatry Psychiatry Severe = 3 Moderate = 2 Severe = 3

Etiology Which of the following interventions Di Giulio, Reissing 2006 is proven to help reduce PMS symptoms? • No abnormal levels of hormones • No hormonal dysregulation 1. Progesterone supplementation • Sensitivity to normal cyclical 2. The antidepressant, bupropion (Wellbutrin) hormonal changes 3. Calcium supplementation 4. Increasing salt intake UCSF Dept. of UCSF Dept. of Psychiatry Psychiatry PMS Treatment with Calcium PMS/PMDD Treatment Thys-Jacobs et al, Am J OB Gyn 1998 Kroll, Rapkin, 2006 • Multi-center, randomized, placebo • Initial approach = basic wellness: controlled study, N=497 – Healthy diet • 600 mg bid x 3 cycles – Stop smoking • 55% had >50% improvement in global sxs – Exercise – 36% with placebo • 48% reduction in total sxs scores – Adequate sleep – 30% with placebo – Stress management • Calcium relieved both emotional & physical sxs • HOWEVER, recent study: SSRI better than UCSF Dept. of UCSF Dept. of Psychiatry Psychiatry Ca or PBO for pts with PMDD (Yonkers, 2013)

Efficacy of SSRIs in PMS PMDD Treatment with SSRIs • Continuous dosing • Luteal phase dosing • AKA Intermittent dosing • Help emotional & physical sxs • In gen’l, respond to lower doses & quicker • Discontinuation sxs rare UCSF Dept. of UCSF Dept. of Psychiatry Psychiatry Margoribanks J et al, Cochran Library, 2013 Yaz for PMDD OCPs for PMDD Yonkers et al, 2005 Joffe, Cohen, Harlow 2003 • Not helpful: Progesterone alone & • Multi-site, DB, RCT most combo OCPs • N=450, all with PMDD, 18-40 yo – May make sxs worse • Daily ratings • Helpful: Yaz • 24 days on & 4 days off (with inert pill) – Drospirenone 3 mg + ethinyl estradiol 20 mcg UCSF Dept. of UCSF Dept. of Psychiatry Psychiatry

Yaz for PMDD Yonkers et al, 2005 • Found signif. diff 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 UCSF Dept. of UCSF Dept. of bleeding Psychiatry Psychiatry How common is depression in “ I feel miserable ” women? Kessler, 2003 32 yo with 6 mo h/o depressed mood and: • 20-25% of all women will experience at -insomnia -low energy least 1 episode of depression in their lives -poor concen. -decr appetite • Boys & girls have equal rates of depression -less interest -passive SI • Beginning with puberty, rates ↑ for girls -Fn at work impaired • Overall, twice as common in women -Sxs began after parents announced div. -Had 1 prior episode depression UCSF Dept. of UCSF Dept. of Psychiatry Psychiatry

One year later... Treatment Plan for “ I feel miserable ” • Course of Cognitive Behavioral Therapy (CBT) • Rx with an SSRI • Depression significantly improved UCSF Dept. of UCSF Dept. of Psychiatry Psychiatry Course of Depression in Pregnancy • Pregnancy NOT protective Cohen et al, 2006 • N = 201 • 10-20% of pregnant women dev MDD • Risk factors for depression in preg: • All with > 4 prior MDD episodes but in full remission – Prior h/o dep • Recurrence during pregnancy if stayed – Poor social support on meds = 26% – Psychosocial stresses • Recurrence if d/c meds = 68% – Ambiv about pregnancy – 50% in 1 st trimester UCSF Dept. of UCSF Dept. of – 90% by end of 2 nd trimester Psychiatry Psychiatry

Treatment of Depression During Pregnancy • Psychotherapy proven effective – Interpersonal Psychotherapy (IPT) – Cognitive Behavioral Therapy (CBT) • Antidep Rx--main areas of concern: – Congenital organ malformations – Adverse effects in neonate – Impact on child’s development: • Cognitive UCSF Dept. of UCSF Dept. of Psychiatry Psychiatry • Behavioral Which is the most true statement TCAs During Pregnancy Yonkers et al, 2009 about antidepressants in pregnancy? 1. SSRIs are completely safe 2. TCAs are contraindicated 3. Not enough data exists to help make an educated recommendation 4. An individualized risk-benefit assessment must guide decision-making 5. SSRIs are contraindicated UCSF Dept. of UCSF Dept. of Psychiatry Psychiatry

Perinatal Effects of SSRIs SSRIs During Pregnancy Bakker, 2012; Diav-Citrin & Ornoy, 2012; El Marroun et al, 2012 Levinson-Castiel, 2006 • Neonatal adaptation syndrome--15-30% • No incr rate of congenital exposed neonates malformations • Multiple sxs reported • BUT, paroxetine may be different – Agitation, jitteriness, sleep disturbance – Cardiac malformations – Tremor – Rigidity – Now Class D per FDA – Feeding problems • Level II UTZ at 16-20 wks – Excessive crying • Typically resolve w/in 48 hrs w/o medical intervention • Consider ↓ or d/c of antidep. prior to UCSF Dept. of UCSF Dept. of Psychiatry Psychiatry delivery Other antidepressants during SSRIs and PPHN Hanley GE & Oberlander RF, 2013 and Wilson et al, 2011 pregnancy Cole et al, 2007; Yonkers et al, 2009 • 1-2/1000 of all live births • Manifests w/in 1 st day of life • Bupropion: no evidence of congenital • Mortality rate ~10% malformations • SSRIs may incr risk 1.8-6X • Duloxetine, escitalopram, • Recent study found key risk factor was C- mirtazapine, nefazodone, venlafaxine, section before onset of labor (incr risk x5) and duloxetine – Fewer reports; no evidence of congenital malformations UCSF Dept. of UCSF Dept. of Psychiatry Psychiatry

Child Development After Fetal Which statement is true? Exposure Nulman et al, 2012 • Prospective study of kids of depressed Child development is adversely impacted by: women 1. In utero exposure to SSRIs 1. Venlafaxine (n=62) 2. Mother’s ability to successfully practice 2. SSRIs (n=62) mindfulness 3. Untreated depression (n=54) 3. Level of severity of mother’s depression 4. Non-depressed Controls on no meds (n=62) 4. Presence of depression in the father • Intelligence and behav outcomes measured when 3-6 yo 5. In utero exposure to heavy metal music • Grps 1, 2 & 3 had lower IQs and incr behav problems than grp 4 • Severity of maternal dep in preg & at UCSF Dept. of UCSF Dept. of testing is what predicted child behav Psychiatry Psychiatry What about risk of autism? What about risk of autism? Rai et al 2013 Rai et al 2013 • Incr risk for ASD if took antidep compared • ASD affect ~1-2% to women with dep who did not • Dysfunctional serotonin signaling may play – Antidep use explained 0.6% of the cases of role in pathogenesis ASD • Swedish study; antidep during preg. • Assoc found; not clear if causation – 1,679 ASD • Hard to determine impact of depression itself – 16,845 controls with data on antidep use – Severity not quantified – More ill pts more likely to be on meds • Unclear if other exposures e.g. Drugs, UCSF Dept. of UCSF Dept. of Psychiatry Psychiatry Etoh...