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Mental Health and Women’s Health

Ellen Haller, M.D. Professor of Clinical Psychiatry UCSF Department of Psychiatry UCSF Dept. of

Psychiatry

Disclosure information

I have nothing to disclose.

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



Premenstrual Syndrome Braverman 2007

•  PMS described for centuries & across cultures; term 1st used in 1950s

•  Most women have some PMS symptoms during some of their ~400 menstrual cycles

•  More significant PMS symptoms in ~30%


Premenstrual Dysphoric Disorder (PMDD) Cunningham J, 2009; Di Giulio, Reissing 2006

•  3-8% •  Starts in 20s; worsens over time •  PMDD dx criteria in syllabus

–  Is now formal dx in DSM-5

•  For up to 90%, PMDD not dx’d •  For ~40% of pts reporting PMDD, correct dx

= premenstrual exacerbation of other d/o •  Need to r/o other psych d/o and hypothy,

then prospectively track sxs


Symptoms 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 Days of period

Symptoms 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 Days of period

Month _____________ Grade each symptom daily:

None = 0 Mild = 1

Moderate = 2 Severe = 3


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

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

Month __April, 2013_____________ Grade each symptom daily:

None = 0 Mild = 1

Moderate = 2 Severe = 3


Etiology Di Giulio, Reissing 2006

•  No abnormal levels of hormones •  No hormonal dysregulation •  Sensitivity to normal cyclical

hormonal changes


Which of the following interventions is proven to help reduce PMS symptoms?

1.  Progesterone supplementation 2.  The antidepressant, bupropion (Wellbutrin) 3.  Calcium supplementation 4.  Increasing salt intake


PMS/PMDD Treatment Kroll, Rapkin, 2006 •  Initial approach = basic wellness:

–  Healthy diet –  Stop smoking –  Exercise –  Adequate sleep –  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

•  HOWEVER, recent study: SSRI better than Ca or PBO for pts with PMDD (Yonkers, 2013)


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


Efficacy of SSRIs in PMS

Margoribanks J et al, Cochran Library, 2013


OCPs for PMDD Joffe, Cohen, Harlow 2003

•  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, 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, 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

bleeding UCSF Dept. of Psychiatry


How common is depression in women? Kessler, 2003

•  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


“I feel miserable” 32 yo with 6 mo h/o depressed mood and: -insomnia -low energy -poor concen. -decr appetite -less interest -passive SI -Fn at work 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...


•  Pregnancy NOT protective •  10-20% of pregnant women dev MDD •  Risk factors for depression in preg:

–  Prior h/o dep –  Poor social support –  Psychosocial stresses –  Ambiv about pregnancy


Course of Depression in Pregnancy Cohen et al, 2006

•  N = 201 •  All with > 4 prior MDD episodes but in full

remission •  Recurrence during pregnancy if stayed

on meds = 26% •  Recurrence if d/c meds = 68%

–  50% in 1st trimester –  90% by end of 2nd trimester



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 • Behavioral


Which is the most true statement 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


TCAs During Pregnancy Yonkers et al, 2009


SSRIs During Pregnancy Bakker, 2012; Diav-Citrin & Ornoy, 2012; El Marroun et al, 2012 •  No incr rate of congenital

malformations •  BUT, paroxetine may be different

– Cardiac malformations – Now Class D per FDA

•  Level II UTZ at 16-20 wks


Perinatal Effects of SSRIs Levinson-Castiel, 2006

•  Neonatal adaptation syndrome--15-30% exposed neonates

•  Multiple sxs reported –  Agitation, jitteriness, sleep disturbance –  Tremor –  Rigidity –  Feeding problems –  Excessive crying

•  Typically resolve w/in 48 hrs w/o medical intervention

•  Consider ↓ or d/c of antidep. prior to delivery


SSRIs and PPHN Hanley GE & Oberlander RF, 2013 and Wilson et al, 2011 •  1-2/1000 of all live births •  Manifests w/in 1st day of life •  Mortality rate ~10% •  SSRIs may incr risk 1.8-6X •  Recent study found key risk factor was C-

section before onset of labor (incr risk x5)


Other antidepressants during pregnancy Cole et al, 2007; Yonkers et al, 2009

•  Bupropion: no evidence of congenital malformations

•  Duloxetine, escitalopram, mirtazapine, nefazodone, venlafaxine, and duloxetine – Fewer reports; no evidence of

congenital malformations


Which statement is true?

Child development is adversely impacted by: 1. In utero exposure to SSRIs 2. Mother’s ability to successfully practice mindfulness 3. Level of severity of mother’s depression 4. Presence of depression in the father 5. In utero exposure to heavy metal music


Child Development After Fetal Exposure Nulman et al, 2012 •  Prospective study of kids of depressed

women 1.  Venlafaxine (n=62) 2.  SSRIs (n=62) 3.  Untreated depression (n=54) 4.  Non-depressed Controls on no meds (n=62)

•  Intelligence and behav outcomes measured when 3-6 yo

•  Grps 1, 2 & 3 had lower IQs and incr behav problems than grp 4

•  Severity of maternal dep in preg & at testing is what predicted child behav


What about risk of autism? Rai et al 2013

•  ASD affect ~1-2% •  Dysfunctional serotonin signaling may play

role in pathogenesis •  Swedish study; antidep during preg.

–  1,679 ASD –  16,845 controls with data on antidep use


What about risk of autism? Rai et al 2013 •  Incr risk for ASD if took antidep compared

to women with dep who did not –  Antidep use explained 0.6% of the cases of

ASD •  Assoc found; not clear if causation •  Hard to determine impact of depression

itself –  Severity not quantified –  More ill pts more likely to be on meds

•  Unclear if other exposures e.g. Drugs, Etoh...


Deciding to Rx Antidep in Pregnancy Yonkers et al, 2009; El Marroun et al, 2012; Diav-Citrin & Ornoy, 2012

•  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 UCSF Dept. of Psychiatry

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


Differential Diagnosis •  Persistent Depressive D/O

–  AKA Dysthymia

•  Bipolar d/o •  Substance abuse/dependence •  Sleep deficit •  Medical conditions

–  Anemia –  Thyroid dysfunction

•  Intimate partner abuse •  Post-partum depression (PPD)


Post-partum depression occurs after what percent of live births?

1.  0-5% 2.  6-10% 3.  11-15% 4.  16-20% 5.  21-25%


Cohen LS. Depress Anxiety. 1998:1:18-26.

Transient, nonpathologic

Medical emergency

Serious, disabling

Postpartum Depression

10-15%

2/3 have onset by 6 wks postpartum

Postpartum Blues

50% to 70%

↑ risk for MDD

Postpartum Psychosis

0.01%

70% are affective (bipolar, MDD)

Spectrum of Postpartum Mood Changes


PPD Risk Factors Bloch et al, 2005 •  Psychosocial stress •  h/o depression •  h/o PMDD •  Prior h/o PPD (50% risk) •  Depression during current pregnancy


Therefore,


Edinburgh Postnatal Dep Scale Cox, 1987

•  10 item questionnaire •  Score of >12 indicates probable PPD •  In public domain; it’s been included in

your syllabus


PPD Management Recommendations Yonkers et al, 2011; Carter et al, 2010; Apter et al, 2011; Studd & Nappi, 2012

•  Reassurance & support •  Postpartum Support International

–  www.postpartum.net

•  Psychotherapy –  Interpersonal Psychotherapy (IPT) – Cognitive Behavioral Therapy (CBT)

•  Medications


Pharmacotherapy for PPD Yonkers et al, 2011; Apter et al, 2011; Studd & Nappi, 2012 •  Relatively few studies have evaluated

antidep specifically for PPD •  No study compares psychotx &

pharmacotx

•  BOTTOM LINE: Assume Rx for PPD has same response as in other depression


Psychotropic Drugs During Lactation Davanzo et al, 2011; Sharma & Sharma, 2012

•  All are excreted in human breast milk •  As a class, have more data in breast-

feeding than any other •  Sertraline, paroxetine, NTP & IMI are

most evidence-based meds •  Great resource: Lactmed (NIH)


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 UCSF Dept. of

Psychiatry

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 Info on meds in breastfeeding (Lactmed)

http://toxnet.nlm.nih.gov

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