Transcript The Medication Dilemma

Psychiatric Illness in the
Perinatal and Postnatal Patient
Jillian Glass, MD
April 8, 2011
No financial relationship with
any pharmaceutical company
Women and Mental Health
• 1 in 5 women will experience a major
depressive episode during her lifetime
• Child bearing years is the most likely time
in a womans life for depression
• 10% - 20% of pregnant women experience
depression
Myths
• Pregnancy is protective against psychiatric
illness
• Pregnancy is “naturally happy” time in life
What is Depression?
• Depressed mood or lack of pleasure (anhedonia)
• At least 4 of the following:
– Changes in appetite
– Changes in sleep
– Problems with concentration/decision making
– Thoughts of death (self injury)
– Lack of energy / daytime fatigue
– Feelings of guilt and hopelessness
– Psychomotor agitation or psychomotor retardation
Complications of Diagnosis
• Overlap in symptoms of “normal”
pregnancy and major depression
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Changes in appetite
Changes in sleep
Fatigue
Problems with concentration
Most Common Symptoms in
Antenatal or Postpartum
Depression
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Sadness
Anxiety/Panic Attacks
Feelings of Guilt and Hopelessness
Insomnia
Thoughts of harming self or baby
Risk Factors
• Biological
– Genetics: personal history of mental illness
– Family history of mental illness
– Unhealthy patterns of sleep, poor nutrition
• Psychological
– Character traits
– Coping skills
Risk Factors
• Social
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Poor support
Marital or family discord
Low socioeconomic status
Recent stressful events
Unplanned or unwanted pregnancy
Postpartum Blues
• Postpartum blues
– Irritability, rapid mood swings, tearfulness,
anxiety
– Transient 2- 14 days
– 85% incidence
– Not interfering with functioning *
– Not requiring medication or therapy
Treatment Options
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Education
Support
Psychotherapy
Medication
ECT
The Medication Dilemma
Expose the mother to risks of
psychiatric illness ?
or
Expose the fetus to side effects of
medication ?
or BOTH ?
The Medication Dilemma
• In a recent multicenter, prospective study, 112
women were taking antidepressants when they
became pregnant, and all discontinued medication
as soon as they discovered their pregnancy
• Around 70% developed depressive symptoms
during course of pregnancy and 50% had started
taking antidepressants again by the time their
babies were born.
Dr. Zachary Stowe
Effects of Untreated Depression
• Suicide:
– Overall less in pregnant women, except in cases of
unwanted pregnancy, being abandoned by partner, or
prior pregnancy loss/death
• Increase in Risky Behaviors:
– Disordered Eating
– Use of Substances: Etoh, Drugs, Tobacco
• Reduced or No Obstetrical Care:
– Phobias
– Decreased energy, hopelessness and amotivation
Effects of Untreated Depression
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Low birthweight/small for gestational age
Low APGAR scores
Delayed fetal heart rate
Smaller head circumference
Developmental delay
Cry more and often, “difficult to console”
Fewer facial expressions
Postpartum Effects on Mother
• Increased likelihoood of postpartum depression
– Occurs 4 wks to 6 mos postpartum, 10-20% incidence
• Postpartum psychosis
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Medical emergency
.7% population at large
.04% population without psychiatric history
9.24% of women with prenatal psych hospitalizations
70% of all cases have history of depression or bipolar
Suicide risk increased 70% in first year postpartum
Infantacide rare but more prevalent with psychosis
Other postpartum effects
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Marital problems
Inadequate parenting
Child abuse
Association of child having behavioral
problems: CD, ODD
• Association of child having depression
– 8% increase in kids of untreated mothers
– 11% decrease in kids of treated mothers
Antidepressants - SSRIs
• Category C – Animal reproduction studies have
shown an adverse effect on the fetus and there are
no adequate and well-controlled studies in
humans, but potential benefits may warrant use of
the drug in pregnant women despite potential
risks.
• Paxil (Category D)
• No medications FDA approved for use during
pregnancy
Fetal and Neonatal
Antidepressant Side Effects
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Respiratory Distress
Jitteriness
Tremor
Decreased muscle tone
Withdrawal effects
Sleep problems
Hypoglycemia
Rare Seizures, arrhythmias
PPHN and SSRIs
• Persistent pulmonary hypertension of the newborn
associated with 3rd trimester exposure to SSRIs
– N. Engl. J. Med. 2006;354:579-87
– Absolute Risk 1%
• Follow up study showed other factors associated
with PPHN
– Pediatrics 2007:120;e272-e82
– BMI, C-Section, Asian or African American
• Swedish Medical Birth Register showed less of a
risk than 2006 study
Breastfeeding
• Most meds are transferred through breast milk,
though found at very low levels.
• Measuring serum levels not recommended
– Lab tests not sensitive
– Look for clinical symptoms instead
• Medication exposure during lactation considerably
lower than transplacental exposure (173 pairs
sertraline, fluoxetine, citalopram, fluvoxamine)
Breastfeeding
• Most TCAs are safe and benzodiazepines exhibit
lower milk/plasma ratios than other classes of
psychotropics
– Avoid Doxepin (respiratory depression)
– BDZ: Monitor for Sedation, poor feeding
• Valproate considered compatible with lactation
– Thrombocytopenia and anemia in 1 of 41 dyads
• Carbamazepine “probably safe”
– Transient cholestatic hepatitis, hyperbilirubinemia
Antidepressants - SSRIs
• Fluoxetine
– Well studied
– 1.2% - 12% estimated percentage of maternal dosage to
breast feeding baby
– No teratogenicity found
• Sertraline
– Fewer reports of neonatal side effects than others
– Benign sleep myoclonus, agitation
– Possible specific association with omphalocele and
septal defects
Antidepressants - SSRIs
• Paroxetine
– 2005 GSK “infants exposed in utero may have a higher
risk of congenital malformations, in particular
cardiovascular defects”
– FDA warnings based on 3 studies 1.5% - 2%
– Motherisk Study in Toronto Study
• Over 3000 cases
• Evidence to suggest there is no association between
the use of paroxetine in pregnancy and risk of
cardiovascular defects in exposed infants
Antidepressants - SSRIs
• Citalopram
– No increased risk of malformations in 1
prospective, controled study and in large
registry data base
• Escitalopram
– Not systematically studied
Antidepressants - SNRIs
• Increase the levels of two neurotransmitters,
serotonin and norepinephrine, in the brain
• Limited Data : no morphologic teratogenicity
found, unknown behavioral
• Venlafaxine, Desvenlafaxine
– Dose dependent release of neurotransmitters
– Possible increased risk of hypertension
– Monitor lipids
• Duloxetine
– Contraindicated in patients with chronic liver disesase
Antidepressants - Other
• Buproprion
– Benefits: no sexual s/e, no weight gain, helps
with smoking cessation, may be more tolerable
– Risks: lowers seizure threshold in mom (1 case
report of possible seizure in baby), insomnia,
may increase risk of miscarriage
• Mirtazapine
– Less nausea, side effect of excessive weight
gain and sedation
Other Psychiatric Illnesses Anxiety
• Includes GAD, Panic Disorder, OCD, PTSD,
Social Anxiety Disorder, Phobias
• Most common disorder 18% and affects women
2x as often as men (OCD M=W)
• Prolonged labor, preterm labor, Low birthweights,
Higher rates of C-section, Heightened startle
response in infants, placental abruption
• Generally thought that anxiety disorders are
exacerbated in postpartum period
Other Psychiatric Ilnesses
• Generalized Anxiety Disorder: Excessive
worry and difficulty controlling the worry
• 3 of the following:
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Irritability
Insomnia
Fatigue
Restlessness
Muscle Tension
Other Psychiatric Illnesses
• Panic Attacks
– Sudden onset episode of intense fear or discomfort that
typically peaks at 10 minutes
– Physical symptoms (4/13)
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Increased heart rate or palpitation; Chest pain or discomfort
Shortness of breath or smothering; Feeling of choking
Nausea or abdominal distress
Shaking or trembling; Paresthesias
Dizzy, faint, lightheaded; Derealization or depersonalization
Sweating; Chills
Fear of losing control, going crazy; Fear of dying
Other Psychiatric Illnesses
• Bipolar Disorder
– Mania: Distinct periods of persistently elevated, elated
or irritable mood, plus 3/4 of the following lasting 4
(hypo) to 7 days:
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Inflated self esteem, grandiosity
Flight of ideas, subjective racing thoughts
Decreased need for sleep
More talkative, pressured
Distractibility
Increase in goal directed activity
Excessive involvement in risky activities (sprees, sexual)
Other Psychiatric Illnesses
• Bipolar Disorder
– 3.9% - 6.4%; M=W
– Women affected in teens and early 20s
– One study showed pregnancy had protective effect, but
those participants may have had milder illness
– Perinatal episodes tend to be depressive
– Postpartum relapse 32% - 67%
– Increased risk of postpartum psychosis up to 46%
Lithium
• Category D: Clear evidence, increased risk of
cardiovascular malformation, 1st trimester exp
• Ebsteins Anomaly – malformed tricuspid valve
• Arrhythmias, hypoglycemia, premature delivery
• Rare: neonatal diabetes insipidus, hypothyroidism,
low muscle tone, lethargy, hepatic abnormalities,
respiratory difficulties and polyhydramnios
• Toxicity: flaccidity, poor suck reflex, lethargy
Lithium
• Suspend lithium before delivery when there
is rapid decrease in vascular volume
• Immediately after delivery, the dosage
should be increased and serum levels
monitored to help prevent postpartum
relapse
Lithium – Suggested Guidelines
• Mild, infrequent episodes – gradually taper prior
to conception
• More severe episodes but moderate risk of relapse
– gradually taper prior to conception but
reinstitute after organogenesis
• Severe and frequent episodes – Continue lithium
and counsel on reproductive risks
• Screening: Level II ultrasound at 16–18 weeks'
gestation, fetal echocardiography
Benzodiazepines
• Category D or X
• Increased risk of fetal cleft lip and cleft palate
(.06%-.07%, absolute risk increased by .01%),
hypotonicity, lethargy, cyanosis, failure to feed
• Irritability, sleep disturbance, temp regulation
problems, jitteryness at withdrawal
• “Floppy infant syndrome” when used shortly
before delivery
Benzodiazepines
• A recent analysis of the Swedish Medical
Birth Register found an association with
preterm births, low birth weight and a
moderate increased risk for congental
malformations. An increase in
pylorostenosis or alimentary tract atresia
was seen, but increase in clefts not
demonstrated
Other Mood Stabilizers
• Lamictal (Category B): m/p ratio equivalent to or
marginally higher than other AEDs; Thrombocytosis,
clefts
• Valproate (Category D): 1-3.8% risk of neural tube
defects, craniofacial and limb abnormalities,
cardiovascular anomalies, “fetal valproate syndrome”
also includes cognitive impairment; Acute neonatal risks:
hepatotoxicity, coagulopathy
• Carbamazepine (Category D): “fetal carbamzepine
syndrome” facial dysmorphism, fingernail hypoplasia
Atypical Antipsychotics
• Risperidone, olanzapine, quetiapine, aripiprazole,
ziprasidone, clozapine (B); All Category C
• First line for schizophrenia, but increasingly used
for bipolar disorder, OCD and treatment-resistent
depression
• Low birth weight, therapeutic abortions
• Typical antipsychotics have more data
– Haldol (mean 1.2mg/day) showed no differences in
fetal viability, birth weight, gestational duration
– Risks to neonate include extrapyramidal side effects,
increased tone and reflexes, jaundice, intestinal obstruct
Thinking of Getting Pregnant
• On medication with mild or no symptoms
for 6 months or greater, may be appropriate
to taper and d/c before becoming pregnant
• May not be appropriate with severe or
recurrent depression
Pregnant and Currently on Medication
• Psychiatrically stable women who want to stay on medication –
discuss risks and benefits
• Women who would like to discontinue medication may attempt
medication tapering and discontinuation if they are not
experiencing symptoms, depending on their psychiatric history.
Women with a history of recurrent depression are at a high risk
of relapse if medication is discontinued.
• Women with recurrent depression or who have symptoms
despite their medication may benefit from psychotherapy to
replace or augment medication.
• 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 Currently Not on
Medication
• Psychotherapy may be beneficial in women
who prefer to avoid antidepressant
medication.
• 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).
Resources
• ACOG Practice Bulletin
– Clinical Management Guidelines for OB/GYNs
– Number 92, April 2008
• Perinatal Mood Disorders: Components of
Care Program 2009