Perinatal Mood and Anxiety Disorders

1. Perinatal Mood and Anxiety Disorders Cort A. Pedersen, M.D. UNC Department of Psychiatry

2. 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.

3. 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.

4. 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.

5. 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.

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.

7. 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.

8. 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).

9. 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.

10. 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.

11. 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.

12. Perinatal Depression and Anxiety: Treatment and Prophylaxis • Stress reduction. • Support groups. • Psychotherapy: interpersonal, cognitive-behavioral, 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

13. Pre & Postpartum Prevalence of Psychiatric Admissions among Women

14. 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.

15. 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).

16. 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

17. 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.

18. 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

19. 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.

20. 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.

21. 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.

22. 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.

23. 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?

24. 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:?

25. 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.

26. 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).

27. 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.

28. 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.

29. 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.

30. 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.

31. 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).

32. 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.

33. 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.

34. 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.

35. 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.