11

Y does X Make A Difference?Reproductive-Related Mood

Disorders

Katherine L. Wisner, M.D., M.S.Norman and Helen Asher Professor of Psychiatry

and Obstetrics and GynecologyDirector, Asher Center for Research and

Treatment of Depressive Disorders Member, Women’s Health Research InstituteMember, Institute for Public Health and MedicineFeinberg School of MedicineNorthwestern University, Chicago IL

22

Epidemiology: Major Depression-

Major Public Health Impact

• Depression is common • Twice as many women are affected as men.• Lifetime, Female (F)=21%; Male (M)=12%• Annual, F=13%, M=8%• Depression is the leading cause of disability

worldwide, and a major contributor to the global burden of disease.

• Depression is associated with suicide.• There are effective treatments for depression!

www.who.int/mediacentre/factsheets/fs369/en/index.html

3333

Personal Disease BurdenPersonal Disease Burden

of Depression of Depression

It was devastating to my whole family. I had It was devastating to my whole family. I had gone through numerous attempts to have a gone through numerous attempts to have a baby and when I did finally have this perfect, baby and when I did finally have this perfect, beautiful, healthy baby -- it all but destroyed beautiful, healthy baby -- it all but destroyed me. I couldn’t hold the baby, I couldn’t do me. I couldn’t hold the baby, I couldn’t do anything for the baby, I couldn’t look at the anything for the baby, I couldn’t look at the baby. Every time I got near her, even the smell baby. Every time I got near her, even the smell of the diapers of the baby-- I would… My knees of the diapers of the baby-- I would… My knees would get weak. I would… I just cried all day would get weak. I would… I just cried all day long and I thought I’d made the worst mistake of long and I thought I’d made the worst mistake of my life. my life.

44

Gender Differences in the Prevalence of Major Depression

Women have twice the rate of MDD as menWomen have twice the rate of MDD as men

Kessler et al (1993) Journal of Affective Disorders

55

Clinical Presentation: Major Depression

For two weeks, most of the day nearly every day, For two weeks, most of the day nearly every day, 5 of these (one must be mood or interest):5 of these (one must be mood or interest):

Depressed moodDepressed mood Diminished interest/pleasureDiminished interest/pleasure Weight loss/ gain unrelated to dietingWeight loss/ gain unrelated to dieting Insomnia/ hypersomniaInsomnia/ hypersomnia Psychomotor agitation/ retardationPsychomotor agitation/ retardation Fatigue or loss of energyFatigue or loss of energy Feelings of worthlessness/guiltFeelings of worthlessness/guilt Diminished ability to concentrateDiminished ability to concentrate Recurrent thoughts of deathRecurrent thoughts of deathNIMH--MDD in Women brochure for patients: NIMH--MDD in Women brochure for patients: www.nimh.nih.gov/health/publications/women-and-www.nimh.nih.gov/health/publications/women-and-

depression-discovering-hope/index.shtmldepression-discovering-hope/index.shtml

66

Pathophysiology Biological DifferencesBiological Differences

Major Depression and Mood Disorders are brain Major Depression and Mood Disorders are brain disorders disorders

Dysregulated neural circuits for control of mood, Dysregulated neural circuits for control of mood, thought, sleep, appetite, and behavior.thought, sleep, appetite, and behavior.

Depression results from multiple genes acting Depression results from multiple genes acting together with environmental factors.together with environmental factors.

Depressive symptoms are associated with ovarian Depressive symptoms are associated with ovarian hormone fluctuation, but no relationship between hormone fluctuation, but no relationship between serum levels and depressed moodserum levels and depressed mood

Affected woman have enhanced neurobiological Affected woman have enhanced neurobiological sensitivity to hormonal fluctuation.sensitivity to hormonal fluctuation.

Most women Most women do notdo not experience significant mood experience significant mood problems during reproductive transitions.problems during reproductive transitions.

77

Pathophysiology:Pathophysiology: Life Stress and TraumaLife Stress and Trauma

Women experience more stressors more frequently than Women experience more stressors more frequently than men. men. • Childhood sexual abuse (6%-33%)Childhood sexual abuse (6%-33%)• Adult sexual assault (estimate 15%)Adult sexual assault (estimate 15%)• Male partner violence (WHO, 15%-71% across 10 Male partner violence (WHO, 15%-71% across 10

countries)countries) Women are more likely to react to stressors with Women are more likely to react to stressors with

depression.depression. Frequent stressors and stress reactivity perpetuate and Frequent stressors and stress reactivity perpetuate and

kindle women’s vulnerability to depression over time. kindle women’s vulnerability to depression over time. Less resource access: Full-time working women earn Less resource access: Full-time working women earn

$0.77 per $1 a man earns: less money for needs of their $0.77 per $1 a man earns: less money for needs of their families, more women living in poverty, and far less families, more women living in poverty, and far less savings for retirement.savings for retirement.

88

Prognosis

Recurrence Risk increases with the Recurrence Risk increases with the number of episodes: number of episodes:

With 1 episode of major depression, With 1 episode of major depression, the woman has a 60% probability of the woman has a 60% probability of another another

If 2 episodes, 70%If 2 episodes, 70%If 3 episodes, 90%, likely to be If 3 episodes, 90%, likely to be

chronic, consider maintenance chronic, consider maintenance treatment treatment

99

Paucity of (any!) Treatment in U.S.Paucity of (any!) Treatment in U.S.

Vesga-Lopez et al, Arch Gen Psychiatry 2008;65(7):805-815

Mental health service utilization among women with Psychiatric Disorders is very low

Mood disorder past 12 months:

Non-pregnant 25.5%

Past-year pregnant 14.3%

1010

What is Bipolar Disorder?What is Bipolar Disorder?

Prevalence=1-1.5%; to 5% for spectrum, M=F Onset in mid to late teens Mania/ hypomania alternates with depression “Plugged in” symptoms: grandiosity, less need

for sleep but not tired, pressured speech, flight of ideas, distractibility, increased involvement in activities, excessive involvement in pleasurable activities with no regard for painful consequences

Postpartum onset particularly common Antidepressant alone risks agitation, rapid

cycling Screen for bipolar disorder (Mood Disorders

Questionnaire) www.dbsalliance.org/pdfs/MDQ.pdf

1111

Depression: Evidence Based Depression: Evidence Based Treatment- PsychotherapyTreatment- Psychotherapy

Several types of short-term (8-16 sessions, Several types of short-term (8-16 sessions, focused psychotherapy)focused psychotherapy)

Patient choice, access, depression severity Patient choice, access, depression severity Interpersonal Psychotherapy targets Interpersonal Psychotherapy targets

interpersonal distress and effect on mood interpersonal distress and effect on mood www.apa.org/divisions/div12/rev_est/ipt_depr.htmlwww.apa.org/divisions/div12/rev_est/ipt_depr.html

Cognitive Behavior Therapy – correct distorted Cognitive Behavior Therapy – correct distorted and dysfunctional automatic thoughtsand dysfunctional automatic thoughtswww.beckinstitute.org/what-is-cognitive-behavioral-www.beckinstitute.org/what-is-cognitive-behavioral-therapytherapy

Dialectical Behavior Therapy--combines Dialectical Behavior Therapy--combines standard CBT techniques with skill building - standard CBT techniques with skill building - distress tolerance, acceptance, mindfulnessdistress tolerance, acceptance, mindfulnesshttp://behavioraltech.org/index.cfmhttp://behavioraltech.org/index.cfm

1212

All Antidepressants have Similar All Antidepressants have Similar EfficacyEfficacy Serotonergic (SSRI-sertraline, fluoxetine; Serotonergic (SSRI-sertraline, fluoxetine; SNRI, venlafaxine)SNRI, venlafaxine)• Comorbid Anxiety DisorderComorbid Anxiety Disorder• Hot flashesHot flashes• Side effects=Sexual dysfunction, weight gain, Side effects=Sexual dysfunction, weight gain,

nausea/ diarrhea, sleep disturbance, apathy and nausea/ diarrhea, sleep disturbance, apathy and decreased motivationdecreased motivation

Norepinephrine (Tricyclics-nortriptyline)Norepinephrine (Tricyclics-nortriptyline)• Serum level is meaningfulSerum level is meaningful• Side effects=Tremor, tachycardia, dry mouth, Side effects=Tremor, tachycardia, dry mouth,

insomnia, weight gaininsomnia, weight gain

Dopamine/Norepinephrine (bupropion)Dopamine/Norepinephrine (bupropion)• Smoking cessation Smoking cessation • Side effects=Agitation, psychosis, weight Side effects=Agitation, psychosis, weight

neutral/ appetite suppressionneutral/ appetite suppression

Personalize Antidepressant Personalize Antidepressant Choice Choice

1313

Environmental Environmental TreatmentsTreatments

Bright Morning Light TherapyBright Morning Light TherapySeasonal and non-seasonal depression Seasonal and non-seasonal depression

30-60 minutes of commercially 30-60 minutes of commercially available, UV-screened bright fluorescent available, UV-screened bright fluorescent light, within 10 mins of awakening light, within 10 mins of awakening

Center for Environmental Therapeutics, tools Center for Environmental Therapeutics, tools at www.cet.org; at www.cet.org; Wirz-Justice et al--Wirz-Justice et al--Chronotherapeutics for Affective Disorders: A Chronotherapeutics for Affective Disorders: A Clinician's Manual for Light and Wake Therapy Clinician's Manual for Light and Wake Therapy

Aerobic Exercise (Aerobic Exercise (>> 30 minutes of moderate 30 minutes of moderate intensity physical exercise, 3 to 5 days per intensity physical exercise, 3 to 5 days per week) week) Dunn et al, Dunn et al, Am J Prev MedAm J Prev Med 2005;28:1-8, 2005;28:1-8, 20052005

1414

The Longitudinal Laboratory of Women’s Lives

MenarcheMenarchePremenstruumPremenstruum

PregnancyPregnancyPostpartumPostpartumMenopauseMenopause

0.00

0.05

0.10

0.15

0.20

0.25

0.30

8 9 10 11 12 13 14 15 16

OR: Gender = 1.63 (1.42-1.89)**P

RO

BA

BIL

ITY

AGE(adapted from Angold and Rutter, 1992)

Boys

Girls

Prevalence of Premenstrual Symptoms

Women of Reproductive Age

Mild Premenstrual Symptoms 75%

PMS 20%-40%

PMDD

3%-8%

1. Steiner M. J Psychiatry Neurosci 2000;25(5):459-468.2. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, 4th ed. 1994.

1717

Premenstrual Dysphoric Disorder

Approximately 5% of menstruating womenApproximately 5% of menstruating women Rule out Major Depression with premenstrual Rule out Major Depression with premenstrual

worsening worsening Average age of onset= 26 yearsAverage age of onset= 26 years Symptoms increase across time until Symptoms increase across time until

menopausemenopause Somatic symptoms typically improve parallel to Somatic symptoms typically improve parallel to

depressive symptomsdepressive symptoms Symptoms return when treatment is stoppedSymptoms return when treatment is stopped SSymptoms of PMDD comparable in severity to ymptoms of PMDD comparable in severity to

major depression- irritability is prominent major depression- irritability is prominent

0

20

40

60

80

100

120

Sequence of Menstrual Cycle Mood Symptoms

= menses

Dep

ress

ion

Sco

re

Follicular phase

LutealPhase

Follicular phase

LutealPhase

Follicular phase

LutealPhase

LutealPhase

Follicular phase

Cycle 1 Cycle 2 Cycle 3 Cycle 4

1919

Premenstrual Dysphoric DisorderPremenstrual Dysphoric Disorder Better than Placebo (SSRI/SNRI)=

Fluoxetine, Sertraline, Citalopram, Paroxetine Venlafaxine/ desmethyl-venlafaxine/ Duloxetine

Continuous OCP under study Dosing – luteal phase Menstrual cycle monitoring Dickerson et al, Am Fam Physician 67(8):1743-1752, 2003

http://www.aafp.org/afp/2003/0415/afp20030415p1743-f2.gifhttp://www.aafp.org/afp/2003/0415/afp20030415p1743-f2.gif

2020

Depression and Sequelae AffectDepression and Sequelae Affect Multiple Domains of Perinatal Multiple Domains of Perinatal

HealthHealth Symptoms of Depression=physiological Symptoms of Depression=physiological

dysregulation dysregulation Appetite and Nutrition Effects Appetite and Nutrition Effects Cognitive changes; attention to self and infant Cognitive changes; attention to self and infant

safety safety Prenatal care compliancePrenatal care compliance Alcohol, drug use Alcohol, drug use Loss of Personal /Family resources Loss of Personal /Family resources Pregnancy Outcomes: low birthweight, preterm Pregnancy Outcomes: low birthweight, preterm

birth (birth (Grote NK et al,Grote NK et al, Arch Gen Psychiatry. Arch Gen Psychiatry. 2010;67(10):1012-1024)2010;67(10):1012-1024)

21212121

Risks are More Heavily Risks are More Heavily Weighted Than BenefitsWeighted Than Benefits

Antidepressant treatment during pregnancy:

Are we asking the right questions?Wisner, Depression and Anxiety: 27:695-698,

2010

2222

Reproductive Outcome Domains

Major birth defects (approx 3% in the general Major birth defects (approx 3% in the general population)population)

Growth EffectsGrowth Effects Behavioral TeratogenicityBehavioral Teratogenicity Neonatal SyndromeNeonatal Syndrome

These domains are impacted by both These domains are impacted by both psychiatric disorders and psychiatric disorders and antidepressants antidepressants

The drug free pregnancy is very rare in The drug free pregnancy is very rare in the USthe US

Summary Points

Physical Malformations-Physical Malformations- Specific Specific defects (if any) are rare and absolute risks defects (if any) are rare and absolute risks are small. are small. Greene, M. F. Greene, M. F. (2007). (2007). Teratogenicity of SSRIs -- Serious Concern or Teratogenicity of SSRIs -- Serious Concern or Much Ado about Little? NEJM 356: 2732-2733 Much Ado about Little? NEJM 356: 2732-2733

Growth- Pregnancy duration, Birth Growth- Pregnancy duration, Birth weight-weight- SGA inconsistently reported with SGA inconsistently reported with SSRI exposure. PTB--a converging finding SSRI exposure. PTB--a converging finding for SSRI exposure-- MDD associated with a for SSRI exposure-- MDD associated with a similar level of risk for PTB similar level of risk for PTB (Wisner et al, Am J (Wisner et al, Am J Psychiatry 166:557-566, 2009Psychiatry 166:557-566, 2009).). SGA and PTB SGA and PTB associated with MDD associated with MDD ((Grote et al, Arch Gen Grote et al, Arch Gen Psychiatry 67(10):1012-1024, 2010)Psychiatry 67(10):1012-1024, 2010)

Summary Points Behavioral TeratogenicityBehavioral Teratogenicity Mental development WNLMental development WNL Offspring exposed to antidepressants similar to controls Offspring exposed to antidepressants similar to controls

in cognitive function, expressive language, mood, in cognitive function, expressive language, mood, activity levels, distractibility, behavior problems, activity levels, distractibility, behavior problems, temperament temperament ((Nulman et al, NEJM 336:258-262, 1997Nulman et al, NEJM 336:258-262, 1997))

Pedersen et al (Pedersen et al (Pediatrics, Feb, 2010Pediatrics, Feb, 2010) normal ) normal milestone development in SSRI exposed vs. depressed milestone development in SSRI exposed vs. depressed and controls. and controls.

Prenatal antidepressant exposure not associated Prenatal antidepressant exposure not associated with behavioral or emotional problems. (with behavioral or emotional problems. (Pedersen, Acta Pedersen, Acta Psychiatrica Scand, Nov, 2012). Psychiatrica Scand, Nov, 2012).

No difference in neuromotor function at 6 months No difference in neuromotor function at 6 months in SSRI exposed vs. controls in SSRI exposed vs. controls (Johnson et al, (Johnson et al, Arch Gen Psych Arch Gen Psych 69:787-794, 2012).69:787-794, 2012).

Casper et al Casper et al ((J Pediatr 142:402-408, 2003J Pediatr 142:402-408, 2003)) found less found less favorable motor (not mental) development in SSRI vs. favorable motor (not mental) development in SSRI vs. depression exposed in toddlersdepression exposed in toddlers

Summary Points

Neonatal Syndrome-Neonatal Syndrome- Time-Time-limited < 2 weeks, rarely requires limited < 2 weeks, rarely requires medical intervention; most commonly medical intervention; most commonly associated agents are associated agents are paroxetine>fluoxetine>sertraline> paroxetine>fluoxetine>sertraline> fluvoxamine= citalopram= escitalopramfluvoxamine= citalopram= escitalopram ((Moses-Kolko et al, JAMA 294:2299-2300, 2005)Moses-Kolko et al, JAMA 294:2299-2300, 2005)

26262626

Optimize Maternal Treatment

Minimum effective dose through pregnancy! Standardized measure throughout

pregnancy to monitor for symptom change Pharmacokinetic changes in psychotropic

drug levels during pregnancy Breastfeeding (Surgeon General’s report;

excess risks with not breastfeeding http://www.ncbi.nlm.nih.gov/books/NBK52680/)

2727

Pregnancy Treatment: Conclusions

There is no 0-risk optionThere is no 0-risk option We will always need more dataWe will always need more data It is impossible to prove 0 additional risk from drug It is impossible to prove 0 additional risk from drug

or depression exposure above general populationor depression exposure above general population There will always be women who require or prefer There will always be women who require or prefer

pharmacologic treatment pharmacologic treatment Pharmacokinetic and Pharmacogenetic studies: Pharmacokinetic and Pharmacogenetic studies:

tools to improve efficacy and reduce side effects tools to improve efficacy and reduce side effects

Postpartum Depression Screening in an

Obstetrical Hospital

10,000 screened, 14% positive on screen

(Edinburgh Postnatal Depression Scale -EPDS) Cox JL, et al. Br J Psychiatry 1987; 150:782-86

The onset of the identified episodes for the women was: - during pregnancy, N=276 (33.4%)- postpartum (within 4 weeks of birth),

N= 331 (40.1%)- prior to pregnancy, N=219 (26.5%) www.MedEdPPD.org www.postpartum.net

Endocrinology of Childbearing

ESTROGENS PROGESTINS

Transdermal Estradiol for Postpartum Depression

Replicate Gregoire et al (1996, Lancet) rapid response to E2 vs. PL with antidepressant comparator

Random assignment to E2 patch, sertraline or PL for 8 weeks

Women with response enter blinded continuation phase through 28 weeks postpartum

Infant growth and developmental outcomes at 6.5 months

84 randomized; no adverse events

Eligibility for Study

Ages 18-45 (855) 99 ASHER Women less than 3 mo postpartum•Breastfeeding or formula feeding•Medically healthy•Not taking an antidepressant •Nonsmoking or <10 cigarettes/day

3232

Depression in Menopausal Depression in Menopausal

TransitionTransition Average age 51 yearsAverage age 51 years Risk for depression in the perimenopause; Risk for depression in the perimenopause;

especially women with previous episodesespecially women with previous episodesEstrogen withdrawal theoryEstrogen withdrawal theory Estrogen enhances serotonergic and Estrogen enhances serotonergic and

noradrenergic transmission noradrenergic transmission Domino theoryDomino theory Somatic symptoms, especially sleep disturbance, Somatic symptoms, especially sleep disturbance,

anxiety, sexual dysfunction, create risk for anxiety, sexual dysfunction, create risk for depression as a down-line effectdepression as a down-line effect

Life stage perspectiveLife stage perspective Changing family or professional roles, Changing family or professional roles,

interpersonal losses, aging and physical illnessinterpersonal losses, aging and physical illness

3333

STRAW +10 StagesMenopause 2012. 19(4): 387-95.

3434

Perimenopausal Depression Treatment

Antidepressants and Psychotherapy are first Antidepressants and Psychotherapy are first lineline

Post-meno. women respond more favorably to Post-meno. women respond more favorably to tricyclics (e.g., nortriptyline) than to SSRI tricyclics (e.g., nortriptyline) than to SSRI Transdermal estradiol (E2), small RCTs positiveTransdermal estradiol (E2), small RCTs positive

•3-12 wk RCTs of E3-12 wk RCTs of E2 2 50-100 ug/d) vs Placebo50-100 ug/d) vs Placebo•68-80% response of E68-80% response of E22 vs 20% to Placebo vs 20% to Placebo

JJoffe et al, N=72offe et al, N=72•8 wk RCT E2 (50 ug/day), zolpidem, Placebo8 wk RCT E2 (50 ug/day), zolpidem, Placebo•Similar improvement across 3 groupsSimilar improvement across 3 groups

Morrison et al, N=72Morrison et al, N=72•E2 (100 mcg/day) E2 (100 mcg/day) notnot efficacious compared to efficacious compared to PL after 8 weeks in PL after 8 weeks in older older (mean=62 years) (mean=62 years) post-menopausal women post-menopausal women

3535

Estradiol Treatment

Not a hormone deficiency: Levels of FSH and E2 do Not a hormone deficiency: Levels of FSH and E2 do not distinguish women with/ without depressionnot distinguish women with/ without depressionResponse to E2 is not predicted by baseline or post-Response to E2 is not predicted by baseline or post-treatment E2 levelstreatment E2 levelsE2 has antidepressant properties E2 has antidepressant properties The mood enhancing effects of E2 occurs The mood enhancing effects of E2 occurs independent of the presence of hot flashesindependent of the presence of hot flashesSSRI/SNRI reduce vasomotor symptoms, but not as SSRI/SNRI reduce vasomotor symptoms, but not as effective as E2effective as E2Proposed StudyProposed Study -- For Transdermal E2 vs. -- For Transdermal E2 vs. Sertraline vs. Placebo RCT: STRAW -1 to +1a and 1b Sertraline vs. Placebo RCT: STRAW -1 to +1a and 1b Hypothesis- E2 stabilizes dramatic fluctuations in E2 Hypothesis- E2 stabilizes dramatic fluctuations in E2 levels, reduces variability levels, reduces variability

Mental Healthis Fundamental to

HealthDavid Satcher, M.D.

We must prioritizethe mental healthof the mothers ofour next generation!

3737

Estradiol Treatment

CVD-risks of HT related to the timing of treatment, CVD-risks of HT related to the timing of treatment, with beneficial/neutral effects for women who with beneficial/neutral effects for women who initiate therapy initiate therapy close to the FMPclose to the FMP. . MDD is a risk factor for CVD, which is the leading MDD is a risk factor for CVD, which is the leading killer of women in the U.S. killer of women in the U.S. Breast cancer, The Endocrine Society Scientific Breast cancer, The Endocrine Society Scientific Statement reported a “worst case scenario” for Statement reported a “worst case scenario” for

increased risk in aincreased risk in a 50-54 year old woman with 5 50-54 year old woman with 5 years of unopposed estrogen from 13/1000 women years of unopposed estrogen from 13/1000 women (no exposure) to 14.94/1000 women(no exposure) to 14.94/1000 women

3838

Estradiol Treatment

Risk of VTERisk of VTE reduced by the use of transdermal E2 reduced by the use of transdermal E2E2 for D-MT offers advantages over SSRIs for VMS, E2 for D-MT offers advantages over SSRIs for VMS, osteoporosis, atrophic vaginitisosteoporosis, atrophic vaginitisSSRI treatment is associated with a significantly SSRI treatment is associated with a significantly increased risk of fracture even after adjustment for increased risk of fracture even after adjustment for depression depression

Inclusion/ Exclusions Acceptability of all 3 interventions Smoke < ½ pack cigarettes per day or are willing to cut

down or quit No clotting disorder or DVT (self or first degree

relatives); cardiac disease, breast cancer Birth control: non-estrogen containing: implanon, depo-provera, progestin-only OCP, IUD, double barrier Bleeding assessment each week; medroxyprogesterone

withdrawal at end of acute phase if no bleed (and no source of progestogen); followed through continuation

Labs: free T4 and TSH; metabolic screen; CBC, platelets; urinalysis; UDS; urine pregnancy test

“Normal” lipids

4040

Resources: Bipolar Disorder Is Your Depressed Patient Bipolar? Kaye NS,

www.jabfm.org/content/18/4/271.full Patient Resource (NIMH):

www.nimh.nih.gov/health/publications/bipolar-disorder/complete-index.shtml

Treatment of Bipolar Disorder: A Guide For Patients and Familieswww.psychguides.com/sites/psychguides.com/files/docs/Bipolar%20Handout.pdf

Famous Women with Bipolar DisorderFamous Women with Bipolar DisorderCarrie Fisher, Patty Duke, Mariette Hartley, Carrie Fisher, Patty Duke, Mariette Hartley, Catherine Zeta-Jones, Jane Pauley, Marilyn Catherine Zeta-Jones, Jane Pauley, Marilyn Monroe, Judy GarlandMonroe, Judy Garland

Resources for PMDD

Steiner M et al. Expert Guidelines for the Steiner M et al. Expert Guidelines for the Treatment of Severe PMS, PMDD, and Treatment of Severe PMS, PMDD, and Comorbidities: the Role of SSRIs. J Comorbidities: the Role of SSRIs. J Women’s Health 2006:15:57-69. Women’s Health 2006:15:57-69.

Information for patients: Information for patients:

www.womensmentalhealth.org/specialty-www.womensmentalhealth.org/specialty-clinics/pms-and-pmddclinics/pms-and-pmdd

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4242

More Information- Pregnancy

Developmental and Reproductive Toxicity: www.toxnet.nlm.nih.gov (DART database) Organization of Teratology Information Specialists

(OTIS) www.otispregnancy.org, (866) 626-OTIS, or (866) 626-6847

ACOG Practice bulletin: Use of psychiatric medications during pregnancy and lactation. Obstetrics and Gynecology 110:1179-1198

Wisner KL et al: Psychiatric Disorders, in Obstetrics: Normal and Problem Pregnancies, 5th edition. Gabbe SG et al, Edss; Elsevier, p 1249-1288, 2007.

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More Information: Postpartum Depression

Miller LJ. Postpartum Depression. Miller LJ. Postpartum Depression.

JAMA 287:762-765, 2002. JAMA 287:762-765, 2002. Wisner KL et al.. Clinical Practice: Postpartum Wisner KL et al.. Clinical Practice: Postpartum

depression. depression. NEJM 347:194-199, 2002.NEJM 347:194-199, 2002. Wisner KL et al. Wisner KL et al. A major public health problem: A major public health problem:

Postpartum depression. Postpartum depression. JAMA 296:2616-2618, JAMA 296:2616-2618, 2006.2006.

Munk-Olsen T. New Parents and Mental Munk-Olsen T. New Parents and Mental Disorders: A Population-Based Register Study.Disorders: A Population-Based Register Study.JAMA 2006;296:2582-2589 JAMA 2006;296:2582-2589

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MedEd PPDMedEd PPD www.MedEdPPD.orgwww.MedEdPPD.org

Professional InformationProfessional Information Provides professionals with tools to screen, Provides professionals with tools to screen,

diagnose, treat, refer, engage women with diagnose, treat, refer, engage women with PPD:PPD: • Interactive case studies Interactive case studies • Provider tools including diagnostic Provider tools including diagnostic

instruments instruments • Video presentations and discussions Video presentations and discussions

Mothers and OthersMothers and Others Patient-oriented section contains: Patient-oriented section contains:

• Easy-to-use online diagnostic test;Easy-to-use online diagnostic test;• The myths and realities of PPD;The myths and realities of PPD;• Experiences of women with PPD; Experiences of women with PPD; • Answers to frequently asked questions from Answers to frequently asked questions from

experts in the fieldexperts in the field

Resources: MenopauseResources: Menopause

Parry BL. Treatment in Psychiatry: Perimeno-pausal Depression. Am J Psych 165:23-27, 2008

North American Menopause Society http://www.menopause.org/

Soares CN, Frey BN. Challenges and Opportunities to manage depressionduring the menopausal transition and beyond. Psychiatric Clin N Am 33:295–308, 2010

4545

4646

Antidepressants:One Dose Does NOT Fit All

<100<100 100100 125 or 125 or 150150

200200

1 1 (4%)(4%)

12 (50%)12 (50%) 4 (17%)4 (17%) 7 7 (29%)(29%)

SERT, mg/day,N=24% remitted

<100<100 100100 125 or 125 or 150150

15 (58%)15 (58%) 7 (27%)7 (27%) 4 (15%)4 (15%)

NTP, mg/day, N=26,% remitted

*Start with 25 mg of sertraline or 25 mg of nortriptyline; half of usual starting dose of any antidepressant

Wisner et al, J Clin Psychopharm 26:353-360, 2006.

4747

Adapted from Kupfer DJ. J Clin Psychiatry. 1991;52(Suppl):28-34.

Evolution of Episode and Evolution of Episode and the ‘5 R’s’ for the ‘5 R’s’ for

Major Depressive Disorder Major Depressive Disorder

Time

Hig

h -

-- S

ymp

tom

Lev

el -

–Lo

w

Normal mood

Symptoms

Depression

Relapse

Response

Remission

RecurrenceRelapse

50% improvement+

+

Recovery

Acute Phase Continuation Maintenance