Transcript PERINATAL DEPRESSION - Maine Association of Psychiatric

PERINATAL MOOD
DISORDERS: Update
on Psychotropic
Prescribing
www.mainepsych.org
Postpartum Depression Project
Disclosures and Thanks
Disclosures:
I do not have any conflicts of interest that
may have any direct bearing on this CME
presentation.
I wish to thank Lee Cohen, M.D. Director of the
Perinatal Psychiatry Clinical Research
Program at MGH, for lending me the slides of
some of the graphics in this presentation
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 :
• 43% relapsed
• 26% who continued meds relapsed (50% in first trimester)
• 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 Antidepressant
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.
• Pregnant women stable on antidepressants need to be
aware of the relapse risk with stopping meds
• This should be discussed when weighing the risk/benefit
ratio of using antidepressants during pregnancy
Cohen LS, et al. JAMA. 2006:295;499-507.
Relapse of Bipolar Disorder During Pregnancy
•
89 women with BPD stable at least 1 month prior to conception, 62
continued treatment, 27 discontinued (treatment was mood stabilizer
=/- antidepressant and/or antipsychotic)
•
71% had at least one mood episode ( usually depressed)
--47% of episodes occurred in the 1st trimester
--85.5 % of those who discontinued treatment
--37% of those who continued treatment
•
Those who discontinued spent 40% of their pregnancy in an illness
state; those who continued only 8.8%
Viguera, et al , Am J Psychiatry, 2008
Relapse of Bipolar Disorder During Pregnancy
Presented at NCDEU, Viguera et al, June 2006
Viguera, et al , Am J Psychiatry, 2008
RISKS OF UNTREATED DEPRESSION DURING
PREGNANCY
• Neonatal risks (low birth weight and small for
gestational age infants
• Obstetrical risks (higher rates of miscarriage, preterm
labor, placental abruption, preeclampsia
• Irritable babies (with high cortisol levels)
• Lack of adequate prenatal care
• Higher use of alcohol and drugs
• SUBSEQUENT POSTPARTUM DEPRESSION
• SUBSEQUENT RECURRENT EPISODES OF DEPRESSION
• SUICIDE
GUIDELINES FOR TREATMENT OF DEPRESSION
DURING PREGNANCY
• Assess the overall risks through evaluation of the patient’s
history, current risk factors and current presentation
• For mild to moderate depression try non-pharmacologic
intervention
• Have an open discussion of the risks and benefits of treatment
with medication
• Consider the risks of inadequately treated depression
• For women who are stable on antidepressants who wish to
discontinue antidepressants, inform them of the risks and
monitor closely. Intervene early at signs of recurrence
• When the decision is made to use medication, select
medications with the best established safety profile.
• Medication decisions should be guided by the patient’s history
of prior medication treatment
• If a woman is already on an SSRI antidepressant that is
working well, continue her on that one; pregnancy is not a
time to change antidepressant s and risk relapse and
exposure to two drugs.
• TCA’s are safe, with nortriptyline being preferred
• Use an adequate dosage, this often increases during the
pregnancy because of the increase in blood volume
• Consider ECT for severely depressed or psychotic women –it
is safe and very effective
Regardless of circumstances, a woman with
suicidal or psychotic symptoms should
immediately see a mental health specialist
for treatment.
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).
FDA LABELING
• FDA Category labeling is often misunderstood
and interpreted to mean that the risk increases
from A to B to C, etc That is NOT the case.
• No distinction is made between human and animal
data
• Often is not updated
• New FDA labeling will be released in 2013 and will
eliminate the categories.
• Pregnancy and lactation subsections would have three
components: a risk summary, clinical considerations and a
data section.
SSRI Use during Pregnancy
• Recent findings and more data inform the pharmacologic
treatment of depression during pregnancy
– Consistent conclusions that the absolute risk of SSRI
exposure in pregnancy is small1-3
– Recent case-control studies reveal inconsistent data
regarding teratogenic risk of individual SSRIs4-9
• Reproductive safety data on SSRIs exceed what is known
about most other medicines used in pregnancy
1
Louik C, et al. N Engl J Med 2007; 2 Einarson TR, Einarson A. Pharmacoepidemiol Drug Saf 2005; 3 Einarson A, et al.
Am J Psychiatry 2008; 4 Alwan S, et al. N Engl J Med 2007; 5 Greene MF. N Engl J Med 2007;
6 Hallberg P, Sjoblom V. J Clin Psychopharmacol 2005; 7Wogelius P, et al. Epidemiology 2006;
8 www.gsk.ca/english/docs-pdf/PAXIL_PregnancyDHCPL_E-V4.pdf Dear Healthcare Professional (3/17/08);
9 www.fda.gov/medwatch/safety/2005/Paxil_dearhcp_letter.pdf Dear Healthcare Professional (3/17/08)
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Antidepressant Drug Treatment During
Pregnancy
• SSRI’s most commonly used
• Largest sample size exists for Prozac and it is
first line
• Then Celexa/Lexapro, then Zoloft and TCA’s
(favored are nortriptyline and desiprimine)
• Accumulating safety data for Wellbutrin and
Effexor
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 supporting absence of
increased risk for malformation
Buproprion registry over 500
Retrospective analysis of 1200 exposed infants
Prospective study of 105 infants
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).
Cole19JA, Modell JG, Haight BR, et al Pharmacoepidemiol Drug Saf. 9 August 2006
Evidence for Increased Risk of Cardiac
Malformations Following Paroxetine Exposure?
• Some Epidemiologic data suggesting increased relative
risk (1.5) associated with first trimester exposure to
paroxetine (VSD, ASD)
• Absolute risk of 1/50 vs. background risk of 1/100
• Resulted in labeling change from category C to D
• Recent data from global teratogen monitoring programs do
no not support increased risks of overall cardiac
malformations
.
Wogelius P, et al. Epidemiology. 2006;17:701-704.
Lennestål R, Källén. J Clin Psychopharmacol. 2007;27:607-613.
Cohen LS, Nonacs R. http://www.womensmentalhealth.org/information/newsletter_2.3.html. Accessed March 17, 2008.
Einarson A, et al. Am J Psychiatry. 2008 Apr 1 [Epub ahead of print].
“Poor Neonatal Adaptation” and SSRI Use
During Pregnancy
• Consistent data: Late trimester exposure to SSRIs is
associated with transient irritability, agitation,
jitteriness, and tachypnea
• Studies do not control for maternal mental health
condition, blinding of exposure in neonatal assessments
• Effectiveness of discontinuing or lowering the dose late
in pregnancy aimed at reducing the risk of neonatal
toxicity has not been prospectively studied
“Poor Neonatal Adaptation” and SSRI Use
During Pregnancy
• No correlation between measures of umbilical cord
blood levels of SSRIS and the risk if 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 continued
• Lowering the dose of antidepressants does, however,
increase the risk for maternal postpartum 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.
Sit, D, et al. Pre-publication communication
Warburton et al, Acta Psychiatr Scand 2010; 121(6): 471-9.
Risk for PPHN Associated With Late Trimester
Exposure to SSRI
Inconsistent Findings:
• One report showed increased risk by 6-fold (Chambers 2006)
(with this highest estimate of 6-fold increase 1% of exposed
infants would be affected)
• 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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SSRI Use vs. Untreated Depression
• Both continuous untreated depression and
continuous SSRI use associated with 20% increase
risk preterm birth
• Women taking SSRIs vs. those with psych histories
vs. controls: those taking SSRI had higher risk of
preterm birth (by only 5 days)
• Depression, SSRI exposure and stopping SSRIs during
pregnancy have been associated with increased
spontaneous abortions
Wisner at al Arch Pediatr Adolesc Med. 2009;163:949–954.
Lund N, Pedersen LH, Henriksen TB. Arch Pediatr Adolesc Med. 2009;163:949–954.
Rahimi R, Nikfar S, Abdollah M. Reprod Toxicol. 2006;22:571–575.
Hemels ME, Einarson A, Koren G, Lanctôt KL, Einarson TR. Ann Pharmacother. 2005;39:803–809.
Gavin AR, Chae DH, Mustillo S, Kiefe CI. J Womens Health (Larchmt). 2009;18:803–811.
Einerson et al, pre publication communication, Marce’ Sociaty Annual meeting, 2010
Zolpidem (Ambien) in Pregnancy
• Evaluated 10,343 women prescribed zolpidem
• Included if prescribed for > 30 days in pregnancy
• Excluded women with prior mental disorders, diabetes,
hypertension coronary artery disease
• Extracted 2497 zolpidem exposed and compared to
matched control group of 12, 485
• Zolpidem exposed had higher rates of LBW, PTD, SGA ,
highest in those receiving Zolpidem > 90 days
• No increase in fetal malformations
• Recommend using alternatives to Ambien for insomnia
during pregnancy
LONGTERM NEUROBEHAVIORAL EFFECTS
• Two studies demonstrating absence of neurobehavioral
differences with TCAs versus fluoxetine in exposed vs nonexposed
children
• Children ages 1 1/2 to 6 years exposed to antidepressants (Prozac
or TCAs) in utero had similar IQ’s language development,
behavioral development, temperament, mood, as those not
exposed
•
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
Pharmacologic Treatment of Pregnant Women
with Bipolar Disorder: Considering the Risks
• Commonly used antimanic agents are either
known teratogens or limited available
reproductive safety data
• Risks of untreated psychiatric illness
• 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
• 1970s Lithium Baby Registry—risk for specific
cardiovascular malformation high; Ebstein’s
anomaly
• Revised risk based on meta-analysis: 1/1000 to
1/2000 (0.05%)
• Relative risk 10 to 20 times the rate in general
population (1/20,000)
• Absolute risk vs relative risk: absolute risk is
small
Cohen
28 LS, et al. JAMA. 1994;271:146-150.
Pregnancy Registries for Anticonvulsants:
and Teratogenic Risk
• North American Antiepileptic Pregnancy Registry
• Lamotrigine Pregnancy Registry
• United Kingdom Epilepsy and Pregnancy Register
• Central Registry of Antiepileptic Drugs and and
Pregnancy (EURAP)
• Australian Pregnancy Registry
Holmes LB, et al. Arch Neurol. 2004;61:673-678.
Meador KJ, et al. Neurology. 2006;67:407-412.
Summary of Findings Across Pregnancy Registries
• Valproic acid (VPA) is associated with the highest risk for all
major malformations
– Risk estimates around 10% and higher1
– Risk appears to be dose-dependent (>1000 mg/d); may be with LTG2,3
– Folic acid supplementation may not be protective against VPAassociated neural tube defects
• Risk is highest with anticonvulsant polytherapy, specifically with
VPA4,5,
• 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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Should Depakote (Valproate) be used in
Pregnancy (or women of child bearing age)?
•
Three year old children of 309 women who took anticonvulsants studied:
Valproate exposed had IQ’s 9 points lower than lamotrigine exposed
Data from several studies suggest VPA exposure is associated with increased risk
for adverse cognitive and neurodevelopmental effects compared with other
anticonvulsants
•
1565 pregnancies in which infants were exposed to valproic acid with 118
malformations
– 14 malformations were more common in infants exposed to valproic acid in
the 1st trimester.
Should Depakote (Valproate) be used in
Pregnancy (or women of child bearing age)?
•
– spina bifida, microcephaly, ventricular and atrial septal defects, tetralogy of
Fallot, cleft palate, hypospadias, club foot and craniosynostosis
Use of valproic acid monotherapy in 37,154 women was associated with
significantly increased risks for 6 of the 14 malformations: Spina bifida, Atrial
septal defect , Cleft palate , Hypospadias , Polydactyly , Craniosynostosis
AMERICAN ACADEMY OF NEUROLOGISTS RECOMMENDS
AGAINST THE USE OF VALPROATE IN PREGNANCY
•
•
•
•
Kimford, JM et al, Cognitive function at 3 years of age after fetal exposure to antepileptic drugs, NEJM; 2009 , 360 (16)
1597-1605
Jentink, J. New England Journal of Medicine, 2010; vol 362: pp 2185-2193.
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 E, et al. Neurology. 2004;62:28-32
Lamotrigine (Lamictal) Monotherapy
Exposure: Increased Risk for Oral Clefts
• Overall risk for major malformations with lamotrigine approximately 2.7%
across several studies; no significant difference from the general population
• North American Antiepileptic Pregnancy Registry showed an increased
incidence of a specific malformation
Oral clefts: 8.9/1000 vs baseline 0.37/1000
• Finding not found in the pooled analysis of 19 other registries
• Absolute risk remains small
Cunnington M, et al. Neurology. Neurology March 22, 2005 64:955-960.
Holmes LB, et al. Neurology 2008 70 (22 part2) 2152-8
Dolk, H et . ;Neurology 2008, 71 (10) 714-22
Antipsychotic Use During Pregnancy
Typical antipsychotics and teratogenic risk:
Data support safety of typical antipsychotics with
respect to teratogenicity
Atypicals and teratogenic risk:
• 151 subjects exposed to different atypicals-60 to
olanzapine, 49 to risperidone, 36 to quetiapine, and 6 to
clozapine-with non-exposed controls, major
malformation rates were not significantly different
between the two groups
Altshuler LL, et al. Am J Psychiatry. 1996;153: 592-606Yaeger 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
Newham, JJ et Br J Psych; 2008, 192(5) 333-7McKenna et al, J. Clin. Psychiatry 2005;66:444-9
Antipsychotic Use During Pregnancy
• Infants exposed to atypical antipsychotics are more likely
to be large for gestational age
Conclusions regarding reproductive safety of
these agents are limited with currently available
data, though no of teratogenicity is evident
based on limited studies
National Pregnancy Registry for Atypical Antipsychotics
1-866-961-2388
Altshuler LL, et al. Am J Psychiatry. 1996;153: 592-606Yaeger 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
Newham, JJ et Br J Psych; 2008, 192(5) 333-7McKenna et al, J. Clin. Psychiatry 2005;66:444-9
Antipsychotic Use During
Pregnancy
New FDA Black Box warning:
• All antipsychotics have been updated to have a black box
warning about the use in pregnancy regarding abnormal
movements (EPS) or withdrawal symptoms in infants
exposed in the third trimester
• Data from FDA adverse Event Reporting System
• 69 cases of withdrawal or EPS with antipsychotics
• Some resolved within hours without treatment; others
required longer hospital stays
Antipsychotic Use During
Pregnancy
Pitfalls:
• This data does not reveal anything about the incidence
• Typical antipsychotics have been used during pregnancy
since the 1950’s
• FDA noted that these cases were confounded by other
variables—other meds, other neonatal and obstetrical
complications
Bottom line:
Be aware of the potential for adverse effects
Balance the benefits and risks , especially that of relapse of a
psychotic illness
Benzodiazepine Use during Pregnancy
• Some evidence for a slight increase in oral
clefts with first trimester exposure
• Infants born to mothers taking high doses in
late pregnancy may show signs of toxicity
• Anxiety is a risk factor for preeclampsia,
preterm labor, low birth weight, PPD; long
term, behavioral, cognitive, developmental
and medical problems in the exposed fetus
Treatment of Bipolar Disorder in Pregnancy
Mild to moderate bipolar disorder:
•
Gradual taper and discontinuation of anti-manic prophylaxis
(lithium, sodium valproate) prior to pregnancy can be considered
•
Reintroduce mood stabilizer as needed or during second trimester;
except for sodium valproate given data for behavioral teratogenicity.
Moderate to severe bipolar disorder:
•
Lithium may be the safest alternative for women dependent on mood
stabilizers
•
For lithium nonresponders consider lamotrigine monotherapy
•
Consider lamotrigine and typical or atypical antipsychotic if
lamotrigine monotherapy ineffective
Cohen LS, J Clin Psychiatry 2007;68 ( suppl 9).
ECT During Pregnancy

Treatment of choice when urgent
management is necessary or illness is life
threatening

Especially recommended in delusional
depression, mania

External fetal monitoring, ultrasonography
increases safety

Requires a comprehensive treatment team
Treatment of Mood Disorders during Pregnancy
• Pregnancy is not protective with respect to new onset or
recurrent mood disorders
• Thoughtful consideration needs to be given to the risks of
untreated psychiatric illness
• Thoughtful treatment decisions can be made regarding the
use of psychotropics during pregnancy
• Weighing the relative risks of medication treatment should
be done on an individualized case by case basis.
• Maintaining euthymic mood during pregnancy is crucial
• NO DECISION IS PERFECT; NO TREATMENT IS RISK FREE.
PPD as a Public Health Problem
• Over 4 million women give birth in America
• One of every 8 new mothers experience
depression
• Over half a million women will suffer postpartum
depression each year
• Most common complication of childbearing
• Causes serious and lasting effects on child health
and family functioning
1 Wisner K et al. N Engl J Med. 2002;347:194-199;
2Wisner K et al. J Clin Psychiatry. 2001;62:82-86.
70
Epidemiology of
Postpartum Episodes
Admissions/Month
60
50
40
30
20
Pregnancy
10
0
–2 Years
– 1 Year
Childbirth
+1 Year
+2 Years
Kendell RE et al. Br J Psychiatry. 1987;150:662-673.
Spectrum of Postpartum Mood Disorders
Postpartum Psychosis(0.10.2%)
Postpartum Depression(10-15%)
Postpartum
Symptom
Severity
Postpartum Blues
(50-85%)
None
Risks of Untreated PPD
To mother:
• Stressful impact on relationship with partner
• Kindling phenomenon---development of a chronic low grade
depression with more susceptibility to repeated episodes of
MDD
• Severe postpartum psychiatric disorder is associated with a
high rate of death from natural and unnatural causes,
particularly suicide
• Suicide risk in the first postnatal year is increased 70-fold
To child:
Risks of Untreated PPD
• Poor weight gain
• Sleep problems
• Less breastfeeding-depressed mothers more likely to discontinue
breastfeeding
• Impaired maternal health and safety practices
• Disruption in the attuned infant-caregiver interactions which promote
brain neurological “wiring”:
– Future , hyperactivity, conduct disorders and school behavior problems
– Delays in language and social development
– Increased risk of depression
– Maternal depression is an “Adverse childhood experience” ACE, often it
is not the only adversity
MATERNAL POST PARTUM MOOD IS ONE OF THE STRONGEST PREDICTORS OF
NEUROCOGNITIVE DEVELOPMENT IN CHILDREN MEASURED UP TO AGE SIX
PRESENTATION OF PPD
CLASSIC SYMPTOMS OF DEPRESSION WITH SOME FEATURES
especially prominent with PPD:
– Women are often unable to sleep even when given the
opportunity to do so
Anxiety symptoms are often a very prominent aspect of PPD
– Frequently have intrusive, obsessional ruminations, or images,
usually focused on the baby, often violent in nature, but they are
egodystonic and there is not a problem with reality testing i.e.
non-psychotic. One study showed 50% of women with PPD had
these. Such obsessional thoughts do not increase the risk of
harm to the baby and are important to distinguish from
psychosis.
POST PARTUM PSYCHOSIS
• Typical onset is within 2 weeks after delivery, first
symptoms often within 48-72 hours
• Earliest signs are restlessness, irritability and
insomnia
• Often very labile in presentation
• Often looks “organic” with a lot of confusion and
disorientation
• Most often consistent with mania or a mixed state
POST PARTUM PSYCHOSIS
• Includes agitation, paranoia, delusions, disorganized
thinking and impulsivity
• Thoughts of harming the baby are frequently driven
by delusions—Child must be saved from harm, child
is malevolent, dangerous, has special powers, is
Satan or God
• Rates of infanticide associated with untreated
postpartum psychosis have been estimated to be as
high as 4% and of suicide as high as 5 %.
TREATMENT OF PPD
Selection of treatment:
•
•
•
•
•
•
•
First requires good evaluation, review of prior history and
assessment for suicidality/dangerousness
individual psychotherapy--CBT /IP Interpersonal and cognitive
behavioral therapy very effective for mild to moderate PPD
support group
community support programs
Medication
ECT
hospitalization
O'Hara MW, et al. Arch Gen Psych. 2000;57:1039-1045.
Stuart S, et al. J Psychother Pract Res. 1995;4:18-29.
Appleby L, et al. BMJ. 1997;314:932-936.
Postpartum Depression: Pharmacologic
Strategies
• Data to support use of serotonergic agents
(sertraline, fluoxetine, venlafaxine, fluvoxamine)
and TCAs (nortriptyline)
• Other antidepressants can also be effective
• Adequate dosage need to be given
• Adequate duration of treatment (>6 months)
• TREAT ANXIETY: Adjunctive anxiolytic agents
(lorazepam, clonazepam) are often needed
Colombo, et al. 1999
Which Antidepressant is the Best ?
The one that is most likely to be effective
• Continue antidepressant used during pregnancy
• Use agent to which patient has responded to in the past
• All SSRIs are secreted into breast milk, but no serious
adverse effects have been reported in association with
this. There have been some anecdotal reports of mild
adverse effects possibly associated with exposure to the
drugs through breast milk
• Caution may be needed with exposure in premature
infants with hepatic immaturity
Use of SSRI’s During Lactation
• Exposure for the infant is lowest for sertraline (Zoloft) and
fluvoxamine (Luvox), somewhat higher for paroxetine (Paxil),
highest with citalopram (Celexa) and fluoxetine (Prozac)
• SSRI’s are present in the infant’s blood stream at very low
levels, not detectable by usual methods. ACOG does not
recommend checking infant serum levels.
• With the current knowledge there is no strong evidence to
recommend one drug over another or rationale to switch
from one SSRI to another to promote safety during
breastfeeding
Use of BZN’s/Hypnotics During Lactation
• Data is somewhat limited
• When measured, exposure through breast milk is
extremely low
• Some anecdotal reports of sedation, poor feeding,
respiratory distress; pooled data show low
incidence of adverse effects
• Diazepam more likely to accumulate in breast
feeding baby
• Less likely to accumulate—lorazepam (Ativan)
clonazepam (Klonopin)
Birnbaum et al; Pediatrics, 1999, July 104 (1)e11
Treatment of Postpartum Bipolar
Disorder
• PROTECT SLEEP! Sleep deprivation – similar to
antidepressants regarding risk of induction of
mania/hypomania (10%)
• Despite the theoretical risk of Stevens-Johnsons
Syndrome with Lamictal, this has not been
reported, Lamictal levels are significant in infant
serum
• Lithium is not generally recommended
• Depakote and tegretol are approved for use during
lactation by the AAP, but should be used with much
caution
TREATMENT OF POSTPARTUM PSYCHOSIS
• Psychiatric/obstetrical emergency
• Treat as affective psychosis—i.e. as Bipolar
disorder
• Requires inpatient hospitalization
• Medication treatment is necessary beginning
with an antipsychotic/mood stabilizer such as
Zyprexa, a traditional mood stabilizer like
lithium or Lamictal, adjunctive bezodiazepines
TREATMENT OF POSTPARTUM PSYCHOSIS
• ECT is very effective and rapid treatment
• Then consider adding a mood stabilizer such
as Lamictal or Lithium
• As 70-90% of women with a prior history of
post partum psychosis relapse with
subsequent pregnancies, prophylactic
treatment either before delivery at 36 weeks
or no later than 48 hours after delivery is
recommended. Lithium has been best
studied
Mood Stabilizers and Lactation
• Lamictal present in breast milk at variable levels; infant
serum levels 20-50 % of maternal . Only one adverse event
reported with daily maternal Lamictal dose of 850 mg.
• Tegretol and Depakote are approved by the AAP for use in
lactating infants. Need very close monitoring for drug levels
and liver function
• Lithium is excreted into breast milk at high levels
– Breastfeeding generally avoided
– Possible as monotherapy with close supervision at lowest possible
dose with close clinical monitoring for signs of toxicity and checking
Li levels, TSH, BUN, Cr
Newport DJ, Pennell PB, Calamaras MR, et al. Pediatrics. 2008. 122(1):e223-e231
Viguera AC, Newport DJ, Ritchie J et al. Am J Psychiatry. 2007: 164(2): 342-345
Yonkers KA, Wisner KL, Stowe Z, et al.Am J Psychiatry. 2004: 161(4): 608-620.
Antipsychotics and Lactation
• Medium to high potency typical antipsychotics
rarely have adverse effects
• Thorazine associated with sedation and
developmental delay
• Clozapine may be concentrated in breast milk–
requires infant blood monitoring
• Atypicals: olanzapine, risperidone, and quetiapine– excretion into breast milk is low
– adverse effects appear to be rare.
Effective treatment of
maternal postpartum
illness is an early
intervention for a child
WEB RESOURCES
•www.mainepsych.org MAPP’s website for the PPD Project
•www.womensmentalhealth.org MGH Center for Women’s
Mental Health
•www.postpartum.net Postpartum Support International
•www.mededppd.org NIMH supported website
•Excellent resource, regularly updated
•9 educational modules aimed at different provider categories
offering CME’s
•www.motherisk.org Motherisk Program of Canada , clinical
research and teaching program on drug and other exposure
during pregnancy and lactation
•www.marce
For more information or resources,
or to get involved with the PPD project:
Please contact me:
P. Lynn Ouellette
[email protected]
Subject line: MAPP PPD Project
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