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Depression in Women              —Improving OutcomesKatherine L. Wisner, M.D., M.S.Director, Women’s Behavioral HealthCARE...
DisclosureI have no financial conflicts of    interest or disclosures.
Major Depression:Public Health Impact The World Health Organization estimated that major depression is the leading cause o...
Gender Differences in Prevalence of        Major DepressionWomen: 1.5-2.5 X rate relative to men 15-54              Kessle...
Improving                    Outcomes   Consider Differential Diagnosis   Treat to Remission; Response at Minimum   Mea...
Major Depression   For two weeks, most of the day nearly every day, 5 of    these (one must be mood or interest):   Depr...
Diff Dx: Bipolar Disorder   Unopposed Antidepressant is not Appropriate, risks    agitation/ rapid cycling   Prevalence=...
Treatment and the ‘5 R’s’ for                      MDD                                                            Remissio...
Measure Symptomatic Improvement:       Free Self-Report Measures   PHQ-9 (Patient Health Questionnaire)    www.integratio...
Evidence Based Interventions:             Psychotherapy   Several types of short-term (12-16 sessions, focused    psychot...
Evidence Based Interventions:            Which Antidepressant?  Neurotransmitters and Impact on Mood, Cognition, and Behav...
Neurotransmitter-Related Side Effects     Serotonin •   Sexual dysfunction •   Weight gain, rarely appetite suppression • ...
Bright Light Therapy   Effective for seasonal (winter)     MDD and non-seasonal MDD   Effective augmentation for    anti...
The Longitudinal Laboratory         of Women’s Lives                    Menarche               Premenstruum               ...
Premenstrual Dysphoric              Disorder   Average age of onset= 26 years   Symptoms increase across time until    m...
Prevalence of Premenstrual                          Symptoms       Menstruating Women                                     ...
Sequence of Menstrual Cycle                        Mood Symptoms                   120                   100Depression Sco...
Premenstrual Dysphoric Disorder   Better than Placebo (SSRI/SNRI)   Fluoxetine   Sertraline   Citalopram   Paroxetine...
Depression Recurrence                during Pregnancy   Recurrence risk for women who either maintained    or discontinue...
Reproductive Outcome              Domains   Major birth defects (approx 3% in the    general population)   Growth Effect...
Summary Points   Intrauterine Fetal Death- No conclusive evidence;    women with SRI and/or NDD exposure have higher risk...
Summary Points   Behavioral Teratogenicity- No differences    in cognitive function, verbal comprehension, expressive    ...
The Clinician’s Conundrum:           Dosing   How do I treat to get the best result for the    maternal-fetal pair?   To...
Screening for Depression                  in an Obstetrical Hospital   N=10,000 screened, 14%+ on screen    (Edinburgh Po...
NIMH-funded StudyWisner KL, Hanusa BH, Perel JM, PeindlKS, Piontek CM, Findling RL, Moses-Kolko EL. Postpartum depression:...
Nortriptyline vs. Sertraline   Response and remission rates did not differ;   At 8 weeks, responders: SERT=56%,    NTP=6...
Antidepressants: One Dose Does not Fit All             Wisner et al, J Clin Psychopharm 26:353-360, 2006.SERT,         <10...
Endocrinology of    ChildbearingESTROGENS     PROGESTINS
Estrogen Treatment ofPostpartum Depression      Gregoire (1996) Lancet
Transdermal Estradiol for          Postpartum Depression   NIMH funded, 80 randomized   Replicate Gregoire et al (1996, ...
Perimenopausal Depression   E2 has psychotropic properties independent of    hormone deficiency/withdrawal   Not a simpl...
Dosing: Estradiol Patch for    Perimenopausal Depression   Schmidt et al 2000    •   3 week RCT of E2 vs Placebo    •   3...
Iterative Steps in a Comprehensive     Detection               Program Model                     Diagnosis                ...
International Biennial Congress of The Marcé Society                  www.marcesociety.com    Acting Together Around Child...
Questions
That’s amazing! Tell me more!
More Information-                        Pregnancy   Developmental and Reproductive Toxicity:    www.toxnet.nlm.nih.gov (...
More Information:                  Postpartum Depression              Miller LJ. Postpartum Depression.    JAMA 287:762-7...
MedEd PPD www.MedEdPPD.orgProfessional Information, Free Provides professionals with the tools to  successfully screen, d...
Resources: Bipolar Disorder   Is Your Depressed Patient Bipolar? Kaye NS, JABFM    www.jabfm.org/content/18/4/271.full  ...
WARNING!Insufficient Medical ResearchCan be Hazardous to your HealthC. Everett Koop, M.D.
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Pm 4.00 wisner

  1. 1. Depression in Women —Improving OutcomesKatherine L. Wisner, M.D., M.S.Director, Women’s Behavioral HealthCAREProfessor of Psychiatry, Obstetrics and Gynecology and Reproductive Sciences, Epidemiology, Clinical and Translational Science, and Women’s StudiesWestern Psychiatric Institute and Clinic/UPMCWisnerKL@upmc.edu
  2. 2. DisclosureI have no financial conflicts of interest or disclosures.
  3. 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. 4. Gender Differences in Prevalence of Major DepressionWomen: 1.5-2.5 X rate relative to men 15-54 Kessler et al (1993) Journal of Affective Disorders
  5. 5. Improving Outcomes 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 Related Depressions (PMDD, Perinatal, Perimenopausal) Provide Self-Help Resources
  6. 6. Major Depression For two weeks, most of the day nearly every day, 5 of these (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. 7. Diff Dx: Bipolar Disorder Unopposed Antidepressant is not Appropriate, risks agitation/ 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 sleep but not tired, pressured speech, flight of ideas, distractibility, increased involvement in goal-directed activities, psychomotor agitation, excessive involvement in pleasurable activities with likelihood of painful consequences Screen for bipolar disorder MDQ (Mood Disorders Questionnaire) www.dbsalliance.org/pdfs/MDQ.pdf
  8. 8. Treatment and the ‘5 R’s’ for MDD Remission Recovery Relapse Recurrence Normal mood Pro gre Relapse + SymptomsSeverity ssi Response o 50% improvement nt + od iso Depression rde r Acute Continuation Maintenance Time Adapted from Kupfer DJ. J Clin Psychiatry. 1991;52(Suppl):28-34.
  9. 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 Depression Scale, for pregnancy/postpartum) www.fcmc.weebly.com/uploads/3/4/8/9/3489838/edinburgh scale.pdf
  10. 10. Evidence Based Interventions: Psychotherapy Several types of short-term (12-16 sessions, focused psychotherapy) Patient choice, access, depression severity Monotherapy or combined with other treatment Interpersonal Psychotherapy targets interpersonal distress and effect on mood www.apa.org/divisions/div12/rev_est/ipt_depr.html Cognitive Behavior Therapy – correct distorted and dysfunctional automatic thoughts www.beckinstitute.org/what-is-cognitive-behavioral-therapy/ Dialectical Behavior Therapy--combines standard CBT techniques with skill building - distress tolerance, acceptance, and mindfulness http://behavioraltech.org/index.cfm Computerized applications
  11. 11. Evidence Based Interventions: Which Antidepressant? Neurotransmitters and Impact on Mood, Cognition, and Behavior Bupropion TCA=desipramine, nortriptyline SNRI=venlafaxine/ desmethylvenlafaxine,SSRI=fluoxetine, sertraline, duoxetinecitalopram/escitalopram, paroxetine; TCA clomipramine Stahl 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. 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. 13. Bright Light Therapy Effective for seasonal (winter) MDD and non-seasonal MDD Effective augmentation for antidepressant partial responses 30-60 minutes of a commercially available, UV-screened bright fluorescent light, within 10 mins of awakening, determine optimal time Center for Environmental Therapeutics, www.cet.org Wirz-Justice et al--Chronotherapeutics for Affective Disorders: A Clinicians Manual for Light and Wake Therapy
  14. 14. The Longitudinal Laboratory of Women’s Lives Menarche Premenstruum Pregnancy Postpartum Menopause
  15. 15. Premenstrual Dysphoric Disorder Average age of onset= 26 years Symptoms increase across time until menopause Symptoms of PMDD comparable in severity to major depression Somatic symptoms typically improve parallel to depressive symptoms Symptoms return when treatment is stopped
  16. 16. Prevalence of Premenstrual Symptoms Menstruating Women Mild 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.
  17. 17. Sequence of Menstrual Cycle Mood Symptoms 120 100Depression Score 80 60 40 20 0 Follicular Luteal Follicular Luteal Follicular Luteal Follicular Luteal phase Phase phase Phase phase Phase phase Phase Cycle 1 Cycle 2 Cycle 3 Cycle 4= menses
  18. 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. 19. Depression Recurrence during Pregnancy Recurrence risk for women who either maintained or discontinued antidepressants proximal to conception (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 suffered recurrent major depressive disorder. Most recurrences emerged rapidly (50% in the first trimester, and 90% by the end of second trimester).
  20. 20. Reproductive Outcome Domains Major birth defects (approx 3% in the general population) Growth Effects Behavioral Teratogenicity Neonatal Syndrome These domains are impacted by both psychiatric disorders and antidepressants
  21. 21. Summary Points Intrauterine Fetal Death- No conclusive evidence; women with SRI and/or NDD exposure have higher risk for miscarriage Physical Malformations- Specific defects (if any) are rare and absolute risks are small. Greene, M. F. (2007). Teratogenicity of SSRIs -- Serious Concern or Much Ado about Little? NEJM 356: 2732-2733 Growth- Maternal Weight Gain, pregnancy duration, infant birth weight- SGA inconsistently reported with SSRI exposure. PTB is a converging finding for SRI exposed neonates-- MDD is associated with the same level of risk for preterm birth. PTB and SGA for depression.
  22. 22. Summary Points Behavioral Teratogenicity- No differences in cognitive function, verbal comprehension, expressive language, mood, activity levels, distractibility, behavior problems, temperament (Nulman et al-- TCA, FLX); Casper et al (2003) and Pederson et al (2010) reported less favorable motor (not mental) development in SSRI exposed vs. depression controls in toddlers. Resolved by 19 months. Neonatal Syndrome- Time-limited < 2 weeks, rarely requires medical intervention; most commonly associated agents are paroxetine>fluoxetine>sertraline> fluvoxamine= citalopram= escitalopram PPHN- Risk increased from 1-2/1000 to 6-12/1000 with exposure to SSRI after 20 weeks gestation; subsequent studies have not consistently replicated this finding
  23. 23. The Clinician’s Conundrum: Dosing How do I treat to get the best result for the maternal-fetal pair? Toxicity is related to dose! Should I keep the dose low to reduce exposure? Does the dose change across pregnancy? Guidance document by FDA in October, 2004 http://www.fda.gov/downloads/Drugs/GuidanceCompliance RegulatoryInformation/Guidances/ucm072133.pdf
  24. 24. Screening for Depression in 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 the women (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. 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. 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 demographic variables ID’d responders from nonresponders Medications similarly efficacious in women with non-postpartum depression
  27. 27. Antidepressants: One Dose Does not Fit All Wisner et al, J Clin Psychopharm 26:353-360, 2006.SERT, <100 100 125 or 150 200mg/day,N=24 1 (4%) 12 (50%) 4 (17%) 7 (29%)% remitted NTP, mg/day, <100 100 125 or 150 N=26, 15 (58%) 7 (27%) 4 (15%) % remitted *Start with 25 mg of sertraline or 25 mg of nortriptyline; half of usual starting dose of any antidepressant
  28. 28. Endocrinology of ChildbearingESTROGENS PROGESTINS
  29. 29. Estrogen Treatment ofPostpartum Depression Gregoire (1996) Lancet
  30. 30. Transdermal Estradiol for Postpartum Depression NIMH funded, 80 randomized Replicate Gregoire et al (1996, Lancet) rapid response to E2 vs. PL with an 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
  31. 31. Perimenopausal Depression E2 has psychotropic properties independent of hormone deficiency/withdrawal Not a simple hormone deficiency: Basal plasma levels E2 do not distinguish women with/without depression Mood enhancing effects of E2 in perimenopausal depression occurs independent of hot flashes Antidepressants decrease hot flashes independent of depressive symptoms
  32. 32. Dosing: Estradiol Patch for Perimenopausal Depression Schmidt et al 2000 • 3 week RCT of E2 vs Placebo • 34 confirmed perimenopausal women • 50 ug/d transdermal E2 • 80% response rate to E2 vs 20% to Placebo Soares et al 2001 • 12 week RCT of E2 vs Placebo • 50 confirmed perimenopausal women • 100 ug/d transdermal E2 • 70% response rate to E2 vs 20% to Placebo
  33. 33. Iterative Steps in a Comprehensive Detection Program Model Diagnosis Treatment engagement Treatment Symptom improvement Improved outcomescourtesy L. Miller (e.g. function, quality of life, parenting, offspring, relationships, family, health, prognosis)
  34. 34. International Biennial Congress of The Marcé Society www.marcesociety.com Acting Together Around Childbirth Paris, October 3-5, 2012 Scientific committee:Prof. Anne Buist, Dr. Nine Glangeaud-Freudenthal (Congress President), Prof. Vivette Glover, Ms. Jane Hanley, Prof. Michael OHara, Dr. Oguz Omay, Dr. Anne Laure Sutter, Prof. Katherine Wisner. INFORMATION & Relations Médicales - Raphaël GASSIN REGISTRATIONS Web: www.info-congres.com
  35. 35. Questions
  36. 36. That’s amazing! Tell me more!
  37. 37. More Information- Pregnancy Developmental and Reproductive Toxicity: www.toxnet.nlm.nih.gov (DART database-free) 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, Niebyl JR, Simpson JL, Galan H, Goetzl L, Jauniaux ERM, Landon M, Editors; Elsevier, pages 1249-1288, 2007.
  38. 38. More Information: Postpartum Depression Miller LJ. Postpartum Depression. JAMA 287:762-765, 2002. www.hfs.illinois.gov/mch www.psych.uic.edu/clinical/HRSA; 1-800-573-6121 Wisner KL et al.. Clinical Practice: Postpartum depression. NEJM 347:194-199, 2002. Wisner KL et al. A major public health problem: Postpartum depression. JAMA 296:2616-2618, 2006. Munk-Olsen T. New Parents and Mental Disorders: A Populatio Based Register Study. JAMA 2006;296:2582-2589
  39. 39. MedEd PPD www.MedEdPPD.orgProfessional Information, Free Provides professionals with the tools to successfully screen, diagnose, treat, refer, and engage women with PPD. These include: • Interactive case studies • Provider tools including diagnostic instruments • Educational video presentations and discussionsMothers and Others, Free The patient-oriented section of the site contains many features: • An easy-to-use online diagnostic test; • Information about the myths and realities of PPD; • Experiences of real women with PPD; • Answers to frequently asked questions from experts in the field; and
  40. 40. Resources: Bipolar Disorder Is Your Depressed Patient Bipolar? Kaye NS, JABFM www.jabfm.org/content/18/4/271.full Patient Resource (NIMH): www.nimh.nih.gov/health/publications/bipolar-disorder/complete-in Treatment of Bipolar Disorder: A Guide For Patients and Families www.psychguides.com/sites/psychguides.com/files/docs/Bipol ar%20Handout.pdf Famous Women with Bipolar Disorder Carrie Fisher, Patty Duke, Mariette Hartley, Catherine Zeta- Jones, Jane Pauley, Marilyn Monroe, Judy Garland
  41. 41. WARNING!Insufficient Medical ResearchCan be Hazardous to your HealthC. Everett Koop, M.D.

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