Transcript Management of Perinatal Depression

Management of Perinatal
Depression
Laurel Romer, M.D.
Primary Care Conference
October 11, 2006
Financial Disclosure
• I have received no financial support for
this presentation.
Learning Objectives
• Understand the scope of perinatal depression.
• Understand predictors of perinatal depression.
• Understand adverse effects/teratogenicity of
antidepressant medications.
• Understand harms associated with untreated
depression in pregnancy.
• Determine when to use antidepressant
medication in the perinatal patient.
Common Patient Scenarios in
Primary Care
• Patient is on antidepressant and is
considering becoming pregnant.
• Patient is pregnant and has a relapse of
depression, is not currently on
antidepressant.
• Patient is postpartum and has depressive
symptoms.
Outline
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Epidemiology
Antidepressants in Pregnancy
Untreated Depression in Pregnancy
Relapse of Depression in Pregnancy
Treatment of Depression in Pregnancy
Treatment of Postpartum Depression
Epidemiology
• In the general population, women ages 1844 have highest rates of depression
• Up to 70% of pregnant women report
depressive symptoms
• 10 – 16% meet criteria for major or minor
depression
3, 9, 10
Epidemiology
• Prevalence of depression in pregnancy:
– 1st trimester: 7.4%
– 2nd trimester: 12.8%
– 3rd trimester: 12.0%
• Prevalence of postpartum depression:
13%
3, 9, 10
Antidepressants in Pregnancy
• Research limited by:
– Small sample sizes
– No randomized, controlled trials
– Reliance on case reports
– Questionable controls
– Difficulty controlling confounding variables
U.S. Food and Drug Administration (FDA) Use-in-Pregnancy ratings
A Controlled studies show no risk. Adequate, well controlled
studies in pregnant women have failed to demonstrate a risk to the
fetus in any trimester of pregnancy.
B No evidence of risk in humans. Adequate, well controlled studies in pregnant
women have not shown increased risk of fetal abnormalities despite adverse
findings in animals, or, in the absence of adequate human studies, animal studies
show no fetal risk. The chance of fetal harm is remote, but remains a possibility.
C Risk cannot be ruled out. Adequate, well-controlled human studies are
lacking, and animal studies have shown a risk to the fetus or are lacking as
well. There is a chance of fetal harm if the drug is administered during
pregnancy; but the potential benefits may outweigh the potential risk.
D Positive evidence of risk. Studies in humans, or investigational or postmarketing data, have demonstrated fetal risk. Nevertheless, potential benefits
from the use of the drug may outweigh the potential risk. For example, the drug
may be acceptable if needed in a life-threatening situation or serious disease for
which safer drugs cannot be used or are ineffective.
X Contraindicated in pregnancy. Studies in animals or humans, or
investigational or post-marketing reports, have demonstrated positive
evidence of fetal abnormalities or risk which clearly outweighs any possible
benefit to the patient.
Antidepressants in Pregnancy
• General Principles:
– Avoid in 1st trimester, if possible
– Monotherapy
– Lowest effective dosage
Antidepressants in Pregnancy
• Specific recommendations:
– SSRIs
• No teratogenic effects with exposure at any time
during pregnancy with fluoxetine, fluvoxamine,
paroxetine and sertraline
• Above SSRIs have been associated with:
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Increased premature delivery
Lower birth weight
Lower Apgar scores
Perinatal complications (with 3rd trimester use)
Poor neonatal adaptation
Increased admission to special care nurseries
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Antidepressants in Pregnancy
• Specific Recommendations:
– TCAs
• No clear association with congenital malformations
– Early studies suggested limb anomalies
– 2002 meta-analysis of >300,000 live births identified no
increase in congenital malformations (TCA/1st trimester)
• Desipramine is preferred TCA
– Less anticholinergic
– Less likely to cause orthostatic hypotension
1, 12
Antidepressants in Pregnancy
• Long term effects on child exposed to
fluoxetine or TCAs in utero:
– Nulman I, et al. NEJM 1997;336:258-62.
• Study followed children to 7 years old
• No diminishment in:
– Global IQ
– Language development
– Motor/behavioral development
Untreated Depression
During Pregnancy
• Harms to mother:
– increased risk of self-injurious or suicidal
behaviors
– contributes to inadequate self-care
– poor compliance with prenatal care
– decreased appetite and consequently lowerthan-expected weight gain
– more likely to smoke and to use either alcohol
or illicit drugs
– Increased risk of postpartum depression
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Untreated Depression
During Pregnancy
• Harms to fetus:
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preterm birth
lower birth weight
smaller head circumference
lower APGAR scores
– Putative mechanisms:
• increased serum cortisol and catecholamine levels in
depression may alter uterine blood flow and induce uterine
irritability
• Dysregulation of the HPA may have a direct effect on fetal
development
• Animal studies suggest stress causes neuronal death and
abnormal development of neural structures in the brain
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Untreated Depression
During Pregnancy
• Harms to mother/fetus:
– Increased interpersonal difficulties in the
family unit
– Disruption of mother-child interactions and
difficulty with attachment
– Behavioral problems in the child
– Disruptions in cognitive and emotional
development in the child
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Relapse of Depression in
Pregnancy
• Cohen LS, et al. JAMA 2006; 295:499-507
revealed:
– 43% relapse rate of depression in pregnancy
• 50% in 1st trimester, 90% by end of 2nd trimester
• 26% relapse in those who continued
antidepressant during pregnancy
• 68% relapse in those who discontinued
antidepressant
• Earlier studies purport higher rate of
relapse (75%)
Relapse of Depression in
Pregnancy
• Of the group of women who discontinued
antidepressant medication prior to
pregnancy
– Had a 5-fold increased risk of relapse over
those who maintained their medication
therapy
– 60% resumed therapy during pregnancy
Predictors of Relapse
• Higher rates of relapse:
– Single status (trend only)
– <32 years old
– Duration of depressive illness >5 years
– Recurrent depressive illness, > 4 episodes
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Relapse of Depression in
Pregnancy
• Guiding principles from this study:
– Women with history of longstanding recurrent
depression may do better maintaining
antidepressant therapy
– With the knowledge that 50% of those women
who discontinue antidepressant prior to
conception do not relapse in the first trimester
– might be able to avoid medication exposure
during period of organogenesis
Consensus Guidelines
• Definitions:
– Mild depression:
• Meets minimum diagnostic criteria
• Patient has mild disability or functions only with
considerable effort
– Severe depression:
• Meets most diagnostic criteria
• Patient has clear-cut, observable disability
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Consensus Guidelines
• Survey methodology:
– 36 American experts in women’s mental
health
– 1 OB/GYN, all others in psychiatry
– Mean of 16 years in practice (4-35 years)
– 83% involved in a clinical trial for mood
disorders in women in the past 5 years
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Consensus Guidelines
• Written questionnaire:
– Sought to identify key decision points in the
treatment of depression in women as well as
all the feasible treatment options
– Requested ratings on 858 treatment options
– Highlighted important clinical questions not
yet definitively answered in the literature
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Consensus Guidelines
• Treatment of Depression in a woman
trying to conceive
– Severe depression
• 90% would treat with antidepressant and
psychotherapy
– Single episode, in remission for 6 months (on
antidepressant)
• 91% advised tapering prior to/during conception
– Recurrent, severe depression
• Continue/switch to “safer” antidepressant
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Consensus Guidelines
• Treatment of Depression in the 1st trimester –
psychotherapy recommended in all scenarios
– Severe, recurrent depression
• 83% would continue antidepressant, switching to “safer”
alternative
– Single, mild episode
• Taper, discontinue antidepressant over several weeks
– Single, severe episode
• No consensus; about half would stop antidepressant
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Consensus Guidelines
• Treatment of Depression in 2nd/3rd
trimesters
– Severe, recurrent depression
• Continue antidepressant through delivery
– Single, severe episode
• 63% would continue antidepressant through
delivery
2
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Postpartum Depression
• Definition:
– A major depressive episode that occurs within
4 weeks after delivery
• Prevalence:
– 12-16% during the 6-12 weeks after delivery
Predictors of Postpartum
Depression
• Meta-analyses including >14,000 women plus
additional studies of 10,000 women revealed
strongest predictors:
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Depression during pregnancy
Anxiety during pregnancy
Stressful life events during pregnancy
Marital discord
Low level of social support
Previous history of depression (25% risk)
Prior history of postpartum depression (50-62% risk)
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Postpartum Depression
• Treatment recommendations:
– Consensus Guidelines
• Severe nonpsychotic postpartum depression
(regardless of breastfeeding status)
– SSRI plus psychosocial interventions
– Involve spouse in psychotherapy sessions (90%)
– Full-time or live-in help for the mother (80-90%)
• Milder postpartum depression
– Psychosocial strategies alone (65%)
– Antidepressants (57%)
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Postpartum Depression
• Treatment recommendations:
– Prophylaxis in women with prior postpartum
depression
• SSRI within 24 hours of delivery yielded marked reduction in
depression recurrence
• Nortriptyline prophylaxis did not reduce rates of postpartum
depression in RCT
– Consensus Guidelines
• 83% recommended antidepressant medication and
psychotherapy after delivery
• Sertraline, treatment of choice, followed by paroxetine
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