Perinatal Mood and Anxiety Disorders

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Perinatal Mood and Anxiety Disorders

• Cort A. Pedersen, M.D.
• UNC Department of Psychiatry

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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.

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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.

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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 ones
  time, feeling trapped, Why did I do this?
• Heightened anxiety due to hyper-vigilance about
  the babys welfare.
• Delayed feelings of love for the baby.

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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.

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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.

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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.

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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).

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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.

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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.

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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.

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Perinatal Depression and Anxiety Treatment and
Prophylaxis

• Stress reduction.
• Support groups.
• Psychotherapy interpersonal, cognitive-behavioral
  , supportive. OHara et al., 2000, Arch Gen
  Psychiatry 57 1039-1045.
• Medication usual txs are generally very
  effective. SSRIs best for prophylaxis.
• Estrogen?
• Light therapy

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Pre Postpartum Prevalence of Psychiatric
Admissions among Women
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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.

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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).

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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
• 
  
  

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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.

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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

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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.

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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.

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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.

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Antidepressants in Pregnancy and Lactation

• SSRIs 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.

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Mood Stabilizers in Pregnancy and Lactation

• Lithium First trimester exposure-0.1 risk of
  Ebsteins 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 gt CBZ)
  but not with LTG (smaller database). Some
  evidence oxcarbazepine safer than VLP.
  Nursing-very low VLP, CBZ breast milk
  concentrations. LTG?

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Anxiolytics During Pregnancy/Lactation

• Diazepam, 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?

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Antipsychotics in Pregnancy/Lactation

• Phenothiazines 1st trimester exposure may
  increase malformation rate from 2.0 to 2.4.
  Aliphatic gt 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.

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Psychotropics in Pregnancy/Lactation General
Considerations

• Explain risks and benefits of medication and
  non-medication treatment approaches, respect the
  mothers wishes, document decision-making.
• Dont use medication unless truly necessary,
  especially during the first trimester.
• Dose medications to adequately treat disorders
  (i.e., dont under-medicate to decrease drug
  exposure).

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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.

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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.

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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.

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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.

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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).

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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.

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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.

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Managing Pregnancy in Women Who Require Chronic
Psychotropics-cont

• If 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.

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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.