Download Psychiatric Disorders and Medications During Pregnancy and the

Perinatal Mood
and Anxiety
Disorders
Cort A. Pedersen, M.D.
UNC Department of
Psychiatry
Prevalence of Perinatal Depressive
and Anxiety Disorders
 Depression:
approximately 14% within
the first 2-3 months postpartum
(similar rate during pregnancy). Half
meet DSM-IV criteria, half RDC
criteria.
 Anxiety: At
least 14 % in postpartum
period combining panic disorder, OCD
and generalized anxiety disorder.
 By
far, the most common serious
medical complications of the perinatal
period.
Obstacles to Recognition and Treatment
of Perinatal Mood/Anxiety Disorders
 High
expectations of joy & happiness with new
baby: cognitive dissonance if dysphoric symptoms
arise.
 Attribution of dysphoria to stress, not assessing
hallmark symptoms.
 Self blame.
 Lack of knowledge about mood and anxiety
disorders. Critical role of antenatal education.
Common Dysphoric Emotional
Experiences in New Mothers
 Mood
lability-blues and euphoria.
 Often unanticipated and sometimes
overwhelming stress of newborn care: loss
of control of one’s time, feeling trapped,
“Why did I do this?”
 Heightened anxiety due to hyper-vigilance
about the baby’s welfare.
 Delayed feelings of love for the baby.
Diagnosing Perinatal Depression:
Hallmark Psychological Symptoms
 Depressive
mood, sadness, tearfulness.
 Diminished interest or pleasure in most
activities (especially in taking care of the baby).
 Feelings of worthlessness or inappropriate
guilt (especially about being an inadequate
mother).
 Recurrent thoughts of death or suicide.
 Edinburgh Postnatal Depression Scale: Cox et
al., 1987, Br J Psychiatry 150: 782-6.
Ambiguous Symptoms
(often due to perinatal physiological changes,
demands of newborn, not depression)
 Changes
in appetite or weight
 Sleep disruption (however, persistent
inability to sleep when the baby is asleep is
a common symptom in postpartum
depression).
 Persistent fatigue.
 Psychomotor retardation or agitation.
 Diminished subjective perception of ability
to think or concentrate.
Biological Risk Factors for
Postpartum Depression
 History
of postpartum depression (up to
50% risk).
 History of depression not associated with
pregnancy (up to 25% risk).
 Depressive symptoms during pregnancy.
 Family history of depression.
 History of premenstrual dysphoric
disorder.
 Postpartum blues.
Do hormones play a role?
 Progesterone
and estrogen levels drop
precipitously postpartum. Cortisol, thyroid and
other large hormonal shifts also occur .
 However, hormone levels and changes in levels
do not correlate with mood symptoms.
 But recent research indicates that women who
get peripartum depression are more sensitive to
hormone fluctuations (Bloch et al., 2000 Am J
Psychiatry 157: 924-930).
Psychosocial Risk Factors for
Perinatal Depression
 Lack
of social support.
 Poor relationship with the father of the
baby.
 Stressful life events.
 Primiparity.
 Adolescence.
 Postpartum Depression Predictors
Inventory-Beck, 1998, JOGNN 27: 39-46.
Postpartum Anxiety Disorders:
Clinical Characteristics
 Panic
disorder:
Intense fear of harm/harming baby.
Palpitations, hyperventilation, sweating,etc
Difficulty caring for, leaving baby.
 OCD:
Intrusive thoughts/images of grievous
harm to baby.
Mother sometimes imagines herself
inflicting harm.
Effects of Pregnancy on the Natural
Course of Anxiety Disorders
 Panic
disorder:
Increased risk of recurrence or
intensification postpartum.
 Obsessive compulsive disorder:
Many women with OCD (perhaps around
40%) have initial onset of symptoms
during pregnancy or the postpartum
period.
Perinatal Depression and Anxiety:
Treatment and Prophylaxis
 Stress
reduction.
 Support groups.
 Psychotherapy: interpersonal, cognitivebehavioral, supportive. O’Hara et al., 2000,
Arch Gen Psychiatry 57: 1039-1045.
 Medication:
usual txs are generally very
effective. SSRIs best for prophylaxis.
 Estrogen?
 Light therapy
Pre & Postpartum Prevalence of
Psychiatric Admissions among Women
Postpartum Psychosis:
Clinical Characteristics
 Incidence:
1-2/1000, first few postnatal weeks.
 90%+ are psychotic mood disorders.
 Mood symptoms: depression, mania, mixed,
cycling. Suicidal impulses.
 Psychotic symptoms: hallucinations, delusions,
thought disorder. Delusion-based
homicidal/infanticidal impulses.
 Symptoms of delirium often present:
disturbances of consciousness, attention,
cognition, perception, fluctuation of symptoms.
Risk Factors for Postpartum Psychosis
 History
of bipolar or schizoaffective
disorder: risk increases with number of
prior episodes and prominence of
psychotic symptoms (perhaps up to a 50%
risk).
 History of postpartum psychosis (50-75%
risk).
Management and Treatment of
Postpartum Psychosis
 Management:
Hospitalize immediately (psychiatric emergency!)
Constant, close observation
Supervise visits with baby
 Treatment:
Mood stabilizers (lithium, valproic acid)
Antipsychotics
Antidepressants (if primarily depressed)
Benzodiazepines (agitation)
ECT
Postpartum Psychosis Prophylaxis
 Medication:
Start mood stabilizers immediately
postpartum or even late in pregnancy.
Estrogen?
 General:
Social support/help network in place.
Patient/family education about symptoms.
Plan of action if symptoms develop.
Assessing the Safety of Psychotropic
Medications in Pregnancy/Lactation
 Prospective,
double blind studies
drug trials are unethical. Therefore,
we are dependent on information
from case reports, retrospective
chart reviews, animal toxicology
studies.
 Best summaries to date of this body
of evidence: Wisner et al., (2002)
NEJM 347: 194-199; Newport et al.
(2004) The APA Textbook of
Psychopharmacology, 3rd Edition
Assessing the Safety of Psychotropic
Medications in Pregnancy/Lactation-cont
A considerable body of evidence accumulated
over the last 2 decades indicates that
fetal/newborn exposure to most classes of
psychotropic medication is relatively safe even
during the first trimester.
 Mounting evidence that stress during
pregnancy, including the stress of untreated
severe psychiatric illness, has adverse effects on
fetal development.

Potential Risks of Treatment with
Psychiatric Medications
 Malformations.
 Behavioral
teratogenicity.
 Drug effects on the newborn- toxicity,
withdrawal.
 Blood volume changes: Drug levels shift
into the sub-therapeutic range during
pregnancy or toxic range postpartum.
Potential Risks of Not Treating With
Psychiatric Medications
 Depression,
other untreated psychiatric
disorders during pregnancy are associated
with poor obstetric outcomes.
 In utero stress retards fetal growth, may
disrupt normal behavioral development.
 Children of mentally ill mothers have more
medical, psychological, and cognitive
problems.
 Increased risk of recurrence and treatment
resistance of illness.
Antidepressants in
Pregnancy and Lactation
relatively safe even during 1st trimester except
paroxetine (increases birth defect rates). Worrisome
recent reports that exposure during late pregnancy
more than doubles prevalence of pulmonary
hypertension in newborns.
 SSRIs (especially sertraline, citalopram, paroxetine)
and TCAs (especially nortriptyline) relatively safe in
breast-feeding. Fluoxetine accumulation, TCA-induced
seizures. Venlafaxine accumulates in milk. Insufficient
information about newer antidepressants, trazodone.
 Bupropion: FDA risk category B.
 MAOIs associated with growth retardation, congenital
malformations.
 SSRIs
Mood Stabilizers in Pregnancy and Lactation
 Lithium:
First trimester exposure-0.1% risk of
Ebstein’s anomaly (10-20 x RR). Safer 2nd and 3rd
trimesters . Increases birth weight. Newborn
hypotonicity, arrhythmias, hypothyroidism, DI.
Contraindicated during nursing.
 Anticonvulsants: First trimester exposure-higher
rates of miscarriage, birth defects (NTD, orofacial
clefts), IUGR, neonate toxicity, cognitive impairment
with VLP & CBZ (VLP > CBZ) but not with LTG
(smaller database). Some evidence oxcarbazepine
safer than VLP. Nursing-very low VLP, CBZ breast
milk concentrations. LTG?
Anxiolytics During Pregnancy/Lactation
other benzos: initial reports that 1st
trimester exposure to diazepam, other benzos increase
risk of oral clefts not substantiated.
 Clonazepam: lowest teratogenicity of all benzos in
animal studies. No clear teratogenicity when used in
pregnant epileptics. Lorazepam: safe track record.
Limited milk penetration. Low-medium doses
considered reasonably safe.
 Risks: infant sedation, hypotonicity, postnatal
withdrawal.
 Alprazolam: some evidence that exposure may
increase oral cleft risk 12 times (0.06% to 0.7%).
 Buspirone:?
 Diazepam,
Antipsychotics in Pregnancy/Lactation
 Phenothiazines
1st trimester exposure may increase
malformation rate from 2.0% to 2.4%. Aliphatic >
piperazine, piperidine. Haloperidol relatively safe.
 Infant toxicity: EPS, bowel obstruction (rare).
 Atypicals: malformation, IUGR rates appear WNLs.
Metabolic, neurodevelopmental effects, neonate
toxicity, breast milk concentrations unknown.
 EPS treatments: Diphenhydramine is probably safest
although birth defects rate somewhat higher with 1st
trimester exposure; increased malformation rate with
benztropine, trihexyphenidyl, and especially
amantadine. Propranolol is reasonably safe.
Psychotropics in Pregnancy/Lactation:
General Considerations
 Explain
risks and benefits of medication
and non-medication treatment approaches,
respect the mother’s wishes, document
decision-making.
 Don’t use medication unless truly
necessary, especially during the first
trimester.
 Dose medications to adequately treat
disorders (i.e., don’t under-medicate to
decrease drug exposure).
Psychotropics in Pregnancy/Lactation:
General Considerations-cont.
 Adjust
doses of some medications (mood
stabilizers, antidepressants) to compensate
for changes in blood volume as pregnancy
advances and postpartum.
 Consider tapering dose or stopping some
medications pre-partum to diminish drug
effects on the newborn, especially if there
are obstetric complications.
Guidelines for Treatment of Major
Depression During Pregnancy/Lactation
 SSRIs
(fluoxetine, sertraline) or secondary
amine tricyclic antidepressants (desipramine,
nortriptyline) during pregnancy or lactation.
Buproprion is probably reasonably safe.
 Monitor TCA blood levels; increase dose as
necessary as pregnancy advances, cut back
dose at parturition.
Guidelines for Treatment of Mania
During Pregnancy/Lactation
 First
trimester: Haloperidol for psychosis,
clonazepam for agitation; if mood
stabilizer is necessary, lithium may be first
choice. ECT.
 Second/Third trimester/Postpartum:
Lithium or anticonvulsants, haloperidol
and/or clonazepam if truly needed.
Continue treatment postpartum if no
obstetric complications. Follow breast-fed
infants closely.
Guidelines for Treatment of Mania During
Pregnancy/Lactation-cont
 Monitor
blood levels of mood stabilizers as
pregnancy advances and increase doses to
maintain effective concentrations.
 At parturition, decrease doses of mood stabilizers
by approximately one third to prevent levels from
rising into the toxic range.
Guidelines for Treatment of Anxiety
Disorders During Pregnancy/Lactation
 Panic
Disorder: SSRIs or secondary amine
TCAs. Clonazepam if a benzodiazepine is
necessary.
 Obsessive-Compulsive Disorder: SSRIs or
clomipramine if SSRIs are ineffective (risk
of hypotension during pregnancy, infant
seizures).
Guidelines for Treatment of Psychosis
During Pregnancy/Lactation
 Haloperidol
would generally be the first
choice although phenothiazines probably
increase risk minimally.
 First choice for controlling EPS is
diphenhydramine. Try to avoid during first
trimester.
Managing Pregnancy in Women
Who Require Chronic Psychotropic
Medication
 Emphasize
the importance of birth control and
planning pregnancies.
 Stop meds during 1st trimester, if feasible.
 Plan A: If possible, taper and stop medication prior
to attempts to conceive, e.g. at the beginning of a
menstrual cycle.
 Plan B: Detect pregnancy as early as possible (2
wks with OTC pregnancy tests), then taper/stop
medication.
Managing Pregnancy in Women Who
Require Chronic Psychotropics-cont
stability requires 1st trimester medication,
consider switching to a less risky medication
that could reasonably prevent relapse (e.g.,
from anticonvulsant to lithium or
haloperidol).
 If a mood stabilizer or lithium is necessary
during the 1st trimester, discuss ultrasound
examination of the fetus at 16-18 wks of
pregnancy and how malformations might be
handled (abortion?) before conception.
 If
Managing Pregnancy in Women Who
Require Chronic Psychotropics-cont
 To
diminish the period off of or on less than
optimal medication, resuming most
psychotropics after the 1st trimester (lithium,
some anticonvulsants?) is reasonably safe.
 Risk of postpartum relapse in women with
history of recurrent mood disorders is
diminished by resuming medication
immediately postpartum or even shortly
prepartum.