Transcript PERINATAL DEPRESSION

PERINATAL MOOD
DISORDERS:
Updates in Treatment
Maya Bulman, MD
Maine Medical Center
April 29, 2011
Updates in Treatment During
Pregnancy
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Depression
Bipolar Disorder
Psychosis
Insomnia
DEPRESSION DURING PREGNANCY
 Between
10-20% of women will
experience significant
depression during pregnancy
 This will be a first episode for
one third
Course of Depression During Pregnancy
Women from 3 specialty centers stable on antidepressants for at
least 3 months prior to pregnancy :
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43% relapsed
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26% who continued meds relapsed (50% in first trimester)
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68% who discontinued meds relapsed
(50 % in the 1st trimester, 90% by the end of the 2nd trimester)
Cohen LS, et al. JAMA. 2006:295;499-507.
Time to Relapse in Patients Who
Maintained or Discontinued
Antidepressants
Percentage of Patients Remaining Well
1
0.9
0.8
0.7
Maintained (N = 82)
0.6
0.5
0.4
Discontinued (N = 65)
0.3
0.2
0.1
0
0
12
24
Gestational Age
Cohen LS, et al. JAMA. 2006:295;499-507.
36
CONCLUSIONS:

Pregnancy puts women with a history of depression at
higher risk of recurrence and is not protective.
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Pregnant women stable on antidepressants need to be
aware of the relapse risk with stopping meds
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This should be discussed when weighing the
risk/benefit ratio of using antidepressants during
pregnancy
Cohen LS, et al. JAMA. 2006:295;499-507.
APA/ACOG Guidelines
“The Management of Depression During
Pregnancy: A Report from the American
Psychiatric Association and The American
College of Obstetricians and
Gynecologists,”
Obstetrics & Gynecology (September 2009)
and General Hospital Psychiatry
(September/October 2009).
Pregnant women currently on medication:
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Those who wish to stay on medication, consult with psychiatrists and
OB/GYN to discuss the risks
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Stable women may attempt discontinuation depending on their history.
Women with a history of recurrent depression are at a high risk of
relapse if medication is discontinued.
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Women with recurrent depression or who have symptoms despite their
medication may benefit from psychotherapy to replace or augment
medication
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Women with severe depression (with suicide attempts, functional
incapacitation, or weight loss) should remain on medication. If a
patient refuses medication, alternative treatment and monitoring
should be in place, preferably before discontinuation
Pregnant and not currently on medication
for depression:

Psychotherapy may be beneficial in women who
prefer to avoid antidepressant medication.
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For women who prefer taking medication, risks
and benefits of treatment choices should be
evaluated and discussed, including factors such as
stage of gestation, symptoms, history of
depression, and other conditions and
circumstances (eg, a smoker, difficulty gaining
weight).
All pregnant women:
Regardless of circumstances, a woman with
suicidal or psychotic symptoms should
immediately see a psychiatrist for
treatment.
Antidepressant Drug Treatment During
Pregnancy
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SSRI’s most commonly used
Largest sample size exists for Fluoxetine
(Prozac) and it is first line
Then Citalopram/Escitalopram
(Celexa/Lexapro), then Sertraline (Zoloft)
and TCA’s (favored are nortriptyline and
desiprimine)
Non-SSRI’s During Pregnancy
• More limited reproductive safety data
available for SNRI’s compared to SSRI’s,
i.e.. venlafaxine, duloxetine
• Data on bupropion includes growing number
of exposures ( >1000) supporting absence of
increased risk for malformation
(overall and cardiac)
http://www.gsk.com/media/paroxetine/ingenix_study.pdf
Chun-Fai-Chan B, Koren G, et al. Am J Obstet Gynecol, March 2005. 192(3).
Cole12JA, Modell JG, Haight BR, et al Pharmacoepidemiol Drug Saf. 9 August 2006
First Trimester Use of Selective Serotonin-Reuptake Inhibitors and
the Risk of Birth Defects
Retrospective study:
Compared 9849 infants with and 5860 infants w/o
birth defects for associations with 1st trimester
SSRI use
SSRIs overall show no increased risk of
craniosynostosis, omphalocoel, heart defects
Individual SSRIs may confer some increased risks for
specific defects which are rare and the absolute
risks are small
Louik et al. NEJM June 28,2007
Risk for PPHN Associated With Late Trimester
Exposure to SSRI
Inconsistent Findings:
•
•
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One report showed increased risk by 6-fold (Chambers 2006)
Lower association seen with Källén and Olausson, 2008
NO association seen by Andrade.et al., 2009
Limitations:
 Small number of SSRI exposures
 Recall bias with respect to early versus late SSRI exposure
 Recent data suggests lower risk than Chambers et al
 PPHN correlated with cesarean section, race, body mass index,
and other factors not related to SSRI use**
** Hernández-Díaz S, et al. Pediatrics. 2007;120:e272-e282.
Kallen , August 2008 ; Pharmacoepidemiol Drug Safety
Chambers CD, et al. N Engl J Med. 2006;354:579-587.
Hernández-Díaz S, et al. Pediatrics. 2007;120:e272-e282
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“Poor Neonatal Adaptation” and SSRI Use
During Pregnancy
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Consistent data: Late trimester exposure to SSRIs is
associated with transient irritability, agitation,
jitteriness, and tachypnea
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Studies do not control for maternal mental health
condition, blinding of exposure in neonatal assessments
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Effectiveness of discontinuing or lowering the dose late
in pregnancy aimed at reducing the risk of neonatal
toxicity has not been studied
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Lowering the dose of antidepressants does, however,
increase the risk for maternal post partum depression
Levinson-Castiel R, et al. Arch Pediatr Adolesc Med. 2006;160:173-176.
Chambers
CD, et al. N Engl J Med. 2006;354:579-587.
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No correlation between measures of umbilical
cord levels of SSRIs and risk of developing
neonatal symptoms
No difference in symptoms between two groups
compared: infants born to mothers who had
taken SSRIs but tapered 2 weeks prior to
delivery vs. those who discontinued
This phenomenon may represent serotonergic
dysfunction rather than medication withdrawal
LONGTERM NEUROBEHAVIORAL
EFFECTS
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Two studies demonstrating absence of neurobehavioral
differences with TCAs versus fluoxetine in exposed vs
nonexposed children
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Children ages 1 1/2 to 6 years exposed to antidepressants
(Fluoxetine or TCAs) in utero had similar IQ’s language
development, behavioral development, temperament, mood, as
those not exposed
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No difference between those exposed during just the first
trimester or throughout the pregnancy
However, depression in the mother was associated with lower
cognitive and language achievement
Nulman I, et al. N Engl J Med. 1997;336:258-262. Nulman I, et al. Am J Psychiatry. 2002;159:1889-1895.
Oberlander TF, et al. J Clin Psychiatry. 2004;65:230-237. Oberlander TF, et al. Arch Pediatr Adolesc
Med. 2007;161:22-29. Misri S, et al. Am J Psychiatry. 2006;163
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If a woman is already on an SSRI antidepressant that is
working well, continue her on that one.
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TCA’s are safe, with nortriptyline being preferred
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Use an adequate dosage, this often increases during the
pregnancy (There is no fetal benefit to decreasing dose prior
to delivery, and this may increase risk of PPD in mother)
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Consider ECT for severely depressed or psychotic women –
it is safe and very effective
Pharmacologic Treatment of Pregnant Women
with Bipolar Disorder: Weighing the Risks
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Commonly used antimanic agents are either
known teratogens or limited available
reproductive safety data
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Risks of untreated psychiatric illness
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Risk of discontinuing maintenance
psychotropic medications
Cohen LS, et al. JAMA. 1994;271:146-150.
Steer RA, et al. J Clin Epidemiol. 1992;45:1093-1099;
Orr ST, et al. Am J Prev Med. 1996;12:459-466;
Suppes T, et al. Arch Gen Psychiatry. 1991;48:1082-1088;
Faedda GL, et al. Arch Gen Psychiatry. 1993;50:448-55;
Baldessarini RJ, et al. Clin Psychiatry. 1996;57:441-448.
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Lithium and Teratogenicity
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1970s Lithium Baby Registry—risk for specific
cardiovascular malformation high; Ebstein’s
anomaly
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Revised risk based on meta-analysis: 1/1000 to
1/2000 (0.05%)
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Relative risk 10 to 20 times the rate in general
population (1/20,000)
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Absolute risk vs relative risk
Cohen LS, et al. JAMA. 1994;271:146-150.
Summary of Findings Across Pregnancy Registries
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Valproic acid (VPA) is associated with the highest risk for all
major malformations
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Risk estimates around 10% and higher1
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Risk appears to be dose-dependent (>1000 mg/d); may be with LTG2,3
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Folic acid supplementation may not be protective against VPAassociated neural tube defects
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Risk is highest with anticonvulsant polytherapy, specifically with
VPA4,5,
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Carbamazepine (CBZ) and LTG are associated with lower risk than
VPA
1. Wyszynski DF, et al. Neurology. 2005;64:961-965.
2. Morrow J, et al. J Neurol Neurosurg Psychiatry. 2006;77:193-198.
3. Cunnington M, et al. Epilepsia. 2007;48:1207-1210.
4. Meador KJ, et al. Neurology. 2006;67:407-412.
5. Holmes LB, et al. Arch Neurol. 2004; 61:673-678.
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Neurobehavioral Teratogenicity and Anticonvulsants
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Data from several studies suggest VPA
exposure is associated with increased risk for
adverse cognitive and neurodevelopmental
effects compared with other anticonvulsants
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Neurobehavioral risk with LTG unknown
Adab N, et al. J Neurol Neurosurg Psychiatry. 2004;75:1575-1583.
Adab N, et al. J Neurol Neurosurg Psychiatry. 2001;70:15-21.
Vinten J, et al. Neurology. 2005;64:949-954.
Gaily
22 E, et al. Neurology. 2004;62:28-32.
Lamotrigine (LTG) Monotherapy Exposure:
Increased Risk for Oral Clefts
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Overall risk for major malformations with LTG approximately 2.7% across
several studies1,2
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North American Antiepileptic Pregnancy Registry showed an increased
incidence of a specific malformation
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Oral clefts: 8.9/1000 vs baseline 0.37/10003
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Finding not corroborated in other registries; further
data needed
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Absolute risk remains small
1. Cunnington M, et al. Neurology. 2005;64:955-960.
2. Meador KJ, et al. Neurology. 2006;67:407-412.
3. Holmes LB, et al. Abstract presented at the 46th Annual Meeting of the Teratology Society. June 24-29, 2006; Tucson, Arizona.
Treatment of Bipolar Disorder in Pregnancy
Mild to moderate bipolar disorder:
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Gradual taper and discontinuation of antimanic
prophylaxis (lithium, sodium valproate) prior to
pregnancy can be considered
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Reintroduce mood stabilizer as needed or during
second trimester; except for sodium valproate given data
suggesting behavioral teratogenicity.
Cohen LS, J Clin Psychiatry 2007;68 ( suppl 9).
Moderate to severe bipolar disorder:
•
Lithium may be the safest alternative for women
dependent on mood stabilizers
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For lithium nonresponders consider lamotragine
monotherapy
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Consider lamotrigine and typical or atypical
antipsychotic if lamotrigine monotherapy ineffective
Antipsychotic Use During Pregnancy
Typicals and teratogenic risk:
Data support safety of typical antipsychotics with respect to
teratogenicity
Atypicals and teratogenic risk:
Postmarketing surveillance data for atypicals , case reports
No increased risk for major malformations
Conclusions regarding reproductive safety of
these agents not possible with currently available data,
though no sign of teratogenicity is evident based on
limited studies
Altshuler LL, et al. Am J Psychiatry. 1996;153: 592-606
Yaeger D, et al. Am J Psychiatry. 2006;163:2064-2070.
.McKenna K, et al. J Clin psychiatry. 2005;66:444-449.
Kulkarni J, et al. Aust N Z J Psychiatry. 2008;42:38-44
Antipsychotic Use During Pregnancy
Largest dataset documenting outcomes of use of
Atypicals in Pregnancy
Examined 713 pregnancies in women who were
receiving Risperidone during pregnancy
21 cases of withdrawal-emergent syndrome including
jitteriness, irritability, feeding problems and
somnolence
No increased rate of spontaneous abortions, structural
malformations and fetal teratogenic risk above that
of the general population.
Evaluating the postmarketing experience of risperidone use during pregnancy: pregnancy and neonatal outcomes.
Drug Saf. 2007;30(3):247-64.
Antipsychotic Use During Pregnancy
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On 2/22/11, the FDA issued a warning against
use of antipsychotics during pregnancy, citing
increased risk of withdrawal symptoms and EPS
Data obtained from FDA’s Adverse Event
Reporting System up to 10/08, including use of
typicals and atypicals (mostly typicals)
A majority of the cases were confounded by
other factors, such as malformations, other
medications, prematurity and complications
Antipsychotic Use During Pregnancy
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“The symptoms of EPS and withdrawal in
newborns may include agitation, abnormally
increased or decreased muscle tone, tremor,
sleepiness, severe difficulty breathing, and
difficulty in feeding. In some newborns, the
symptoms subside within hours or days and do
not require specific treatment; other newborns
may require longer hospital stays.”
FFDA Drug Safety Communication: Antipsychotic drug labels updated on use during pregnancy and risk of abnormal muscle movements and withdrawal symptoms in newborns1
Sleep Disturbance in Pregnancy
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25% of women in 1st trimester
75% in 3rd trimester
Poor sleep is strongly correlated with depression
Insomnia is more prevalent in depressed women who
are untreated vs. women who are treated in week 20
There is no difference at week 36, meaning most
women experience sleep disturbance in the 3rd trimester
Speaks to the importance of treating underlying mood
disorder
Field 2007, Katherine Wisner, MD, PhD
Zolpidem Use in Pregnancy
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Large Taiwanese study looked at 2,497 women
without a history of mental illness, who used
Zolpidem during pregnancy for at least 30 days
(with an age matched comparison group)
This study showed increased rates of adverse
pregnancy outcomes including: low birth weight,
preterm delivery, small for gestational age babies
and increased rates of C-section deliveries.
There was no increase in congenital anomalies
Zolpidem Use in Pregnancy
Hypothesis include:
Zolpidem causes the pituitary to release
vasopressin and oxytocin resulting in uterine
vasoconstriction
GABAergic agonists cause respiratory depression
 Highest risk of adverse outcome in women who
took Zolpidem >90 days
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Wang LH, Lin HC, Lin CC , Chen YH & Lin HC. Increased Risk of Adverse Pregnancy Outcomes in Women Receiving Zolpidem During Pregnancy. Clin
Pharm Ther 88:3, 369-374 (2010).
Treatment of Sleep Disturbance in
Pregnancy
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Due to these findings, the authors suggest
avoiding use of Zolpidem in pregnancy when
possible. Other medication options for sleep
with safety data in pregnancy are the tricyclic
antidepressants and the benzodiazepines. Other
options for addressing sleep problems during
pregnancy include cognitive behavioral therapy,
improving sleep hygiene and addressing
underlying mood disorders.
Summary of
Treatment of Mood Disorders During Pregnancy
consideration needs to be given to the risks of untreated
psychiatric illness
relative risks of pharmacologic treatment during
pregnancy is best carried out on a case by case basis
decision is risk free
a euthymic mood during pregnancy is extremely
important
Thank You
Questions?