- 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/[email protected]
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,