1. Depression in WomenImproving OutcomesKatherine L. Wisner, M.D., M.S.Director, Womens Behavioral HealthCAREProfessor of Psychiatry, Obstetrics and Gynecologyand Reproductive Sciences, Epidemiology, Clinicaland Translational Science, and Womens StudiesWestern Psychiatric Institute and Clinic/UPMCWisnerKL@upmc.edu

2. DisclosureI have no financial conflicts ofinterest or disclosures. 3. Major Depression:Public Health Impact The World Health Organization estimated that major depression is the leading cause of disease- related disability among women world-wide.(Murray & Lopez, 1996) 4. Gender Differences in Prevalence ofMajor DepressionWomen: 1.5-2.5 X rate relative to men 15-54Kessler et al (1993) Journal of Affective Disorders 5. ImprovingOutcomes Consider Differential Diagnosis Treat to Remission; Response at Minimum Measure Symptom Improvement Use Evidence Based Interventions Personalize Antidepressant Choice to the Woman Optimize the Dose Special Considerations for Reproductive RelatedDepressions (PMDD, Perinatal, Perimenopausal) Provide Self-Help Resources 6. Major Depression For two weeks, most of the day nearly every day, 5 ofthese (one must be mood or interest): Depressed mood Diminished interest/pleasure Weight loss/ gain unrelated to dieting Insomnia/ hypersomnia Psychomotor agitation/ retardation Fatigue or loss of energy Feelings of worthlessness/guilt Diminished ability to concentrate Recurrent thoughts of deathNIMH--MDD in Women for patients:www.nimh.nih.gov/health/publications/women-and-depression-discovering-hope/index.shtml 7. Diff Dx: Bipolar Disorder Unopposed Antidepressant is not Appropriate, risksagitation/ rapid cycling Prevalence=1-1.5%; to 5% for spectrum, Males=Females Mania/ hypomania alternate with depressive episodes. Onset in mid to late teens Postpartum onset particularly common Plugged in symptoms: grandiosity, less need for sleepbut not tired, pressured speech, flight of ideas,distractibility, increased involvement in goal-directedactivities, psychomotor agitation, excessive involvement inpleasurable activities with likelihood of painfulconsequences Screen for bipolar disorder MDQ (Mood DisordersQuestionnaire) www.dbsalliance.org/pdfs/MDQ.pdf 8. Treatment and the 5 Rs forMDDRemission RecoveryRelapse Recurrence Normal moodProgre Relapse + SymptomsSeverityssi Responseo 50% improvement nt+ odiso Depression rder AcuteContinuation Maintenance Time Adapted from Kupfer DJ. J Clin Psychiatry. 1991;52(Suppl):28-34. 9. Measure Symptomatic Improvement: Free Self-Report Measures PHQ-9 (Patient Health Questionnaire)www.integration.samhsa.gov/images/res/PHQ%20-%20Questions.pdf CES-D (Center for Epidemiologic Studies-Depression Screen www.depression-help-resource.com/cesd-depression-test.pdf EPDS (Edinburgh Postnatal DepressionScale, for pregnancy/postpartum)www.fcmc.weebly.com/uploads/3/4/8/9/3489838/edinburghscale.pdf 10. Evidence Based Interventions: Psychotherapy Several types of short-term (12-16 sessions, focusedpsychotherapy) Patient choice, access, depression severity Monotherapy or combined with other treatment Interpersonal Psychotherapy targets interpersonaldistress and effect on moodwww.apa.org/divisions/div12/rev_est/ipt_depr.html Cognitive Behavior Therapy correct distorted anddysfunctional automatic thoughtswww.beckinstitute.org/what-is-cognitive-behavioral-therapy/ Dialectical Behavior Therapy--combines standard CBTtechniques with skill building - distress tolerance,acceptance, and mindfulnesshttp://behavioraltech.org/index.cfm Computerized applications 11. Evidence Based Interventions:Which Antidepressant?Neurotransmitters and Impact on Mood, Cognition, and BehaviorBupropion TCA=desipramine, nortriptyline SNRI=venlafaxine/ desmethylvenlafaxine,SSRI=fluoxetine, sertraline, duoxetinecitalopram/escitalopram, paroxetine; TCA clomipramineStahl SM. Essential Psychopharmacology. 2nd ed. New York, NY: Cambridge University Press; 2000.Foote SL et al. In: Bloom FE, Kupfer CJ, eds. Psychopharmacology. 1995. 12. Neurotransmitter-Related Side Effects Serotonin Sexual dysfunction Weight gain, rarely appetite suppression Nausea/ diarrhea Sleep disturbance Apathy and decreased motivation Norepinephrine Tremor Tachycardia Dry Mouth Insomnia Dopamine Agitation Psychosis Appetite suppression 13. Bright Light Therapy Effective for seasonal (winter) MDD and non-seasonal MDD Effective augmentation forantidepressant partial responses 30-60 minutes of a commerciallyavailable, UV-screened brightfluorescent light, within 10 mins ofawakening, determine optimal time Center for Environmental Therapeutics,www.cet.org Wirz-Justice et al--Chronotherapeutics forAffective Disorders: A Clinicians Manual for Lightand Wake Therapy 14. The Longitudinal Laboratory of Womens LivesMenarche Premenstruum PregnancyPostpartumMenopause 15. Premenstrual DysphoricDisorder Average age of onset= 26 years Symptoms increase across time untilmenopause Symptoms of PMDD comparable in severity tomajor depression Somatic symptoms typically improve parallelto depressive symptoms Symptoms return when treatment is stopped 16. Prevalence of PremenstrualSymptoms Menstruating Women Mild Symptoms 75% PMS 20%-40%PMDD3%-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. 17. Sequence of Menstrual CycleMood Symptoms 120 100Depression Score 80 60 40 200 Follicular Luteal FollicularLuteal FollicularLuteal FollicularLuteal phasePhasephase Phasephase Phasephase Phase Cycle 1 Cycle 2Cycle 3Cycle 4= menses 18. Premenstrual Dysphoric Disorder Better than Placebo (SSRI/SNRI) Fluoxetine Sertraline Citalopram Paroxetine Venlafaxine/ desmethyl-/ Duloxetine Dosing luteal phase http://www.womensmentalhealth.org/specialty-clinics/pms-and-pmdd/ 19. Depression Recurrenceduring Pregnancy Recurrence risk for women who either maintainedor discontinued antidepressants proximal toconception (Cohen et al- JAMA. 2006;295:499-507)Significantly more women who discontinued(44/65, 68%) compared to women who maintained(21/82, 26%) antidepressant treatment sufferedrecurrent major depressive disorder. Most recurrences emerged rapidly (50% in the firsttrimester, and 90% by the end of second trimester). 20. Reproductive OutcomeDomains Major birth defects (approx 3% in thegeneral population) Growth Effects Behavioral Teratogenicity Neonatal SyndromeThese domains are impacted byboth psychiatric disorders andantidepressants 21. Summary Points Intrauterine Fetal Death- No conclusive evidence;women with SRI and/or NDD exposure have higher risk formiscarriage Physical Malformations- Specific defects (if any)are rare and absolute risks are small. Greene, M. F. (2007).Teratogenicity of SSRIs -- Serious Concern or Much Adoabout Little? NEJM 356: 2732-2733 Growth- Maternal Weight Gain, pregnancyduration, infant birth weight- SGA inconsistentlyreported with SSRI exposure. PTB is a converging findingfor SRI exposed neonates-- MDD is associated with thesame level of risk for preterm birth. PTB and SGA fordepression. 22. Summary Points Behavioral Teratogenicity- No differencesin cognitive function, verbal comprehension, expressivelanguage, mood, activity levels, distractibility, behaviorproblems, temperament (Nulman et al-- TCA, FLX); Casperet al (2003) and Pederson et al (2010) reported lessfavorable motor (not mental) development in SSRI exposedvs. depression controls in toddlers. Resolved by 19 months. Neonatal Syndrome- Time-limited < 2 weeks,rarely requires medical intervention; most commonlyassociated agents are paroxetine>fluoxetine>sertraline>fluvoxamine= citalopram= escitalopram PPHN- Risk increased from 1-2/1000 to 6-12/1000 withexposure to SSRI after 20 weeks gestation; subsequentstudies have not consistently replicated this finding 23. The Clinicians Conundrum: Dosing How do I treat to get the best result for thematernal-fetal pair? Toxicity is related to dose! Should I keep thedose low to reduce exposure? Does the dose change across pregnancy? Guidance document by FDA in October, 2004http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm072133.pdf 24. Screening for Depressionin an Obstetrical Hospital N=10,000 screened, 14%+ 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 thewomen (N=826) 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 25. NIMH-funded StudyWisner KL, Hanusa BH, Perel JM, PeindlKS, Piontek CM, Findling RL, Moses-Kolko EL. Postpartum depression: Arandomized trial of sertraline vs.nortriptyline. J Clin Psychopharm26:353-360, 2006.8 week acute phase parallel design,6 month continuation phase,no placebo 26. Nortriptyline vs. Sertraline Response and remission rates did not differ; At 8 weeks, responders: SERT=56%,NTP=69%: remitters SERT=46%, NTP=48% Time to response and remission did not differ Psychosocial functioning improved similarly The total side effect burden of each drug similar No clinical (including O/C) or demographicvariables IDd responders from nonresponders Medications similarly efficacious in women withnon-postpartum depression 27. Antidepressants: One Dose Does not Fit All Wisner et al, J Clin Psychopharm 26:353-360, 2006.SERT,