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

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 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). 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 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, cognitive- behavioral, supportive. O Hara et al., 2000, Arch Gen Psychiatry 57: 1039-1045. 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; 199; Newport et al. (2004) The APA Textbook of Psychopharmacology, 3rd Edition

Assessing the Safety of Psychotropic Medications in Pregnancy/Lactation-contcont 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 SSRIs relatively safe even during 1 st 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.

Mood Stabilizers in Pregnancy and Lactation Lithium: First trimester exposure-0.1% risk of Ebstein s anomaly (10-20 x RR). Safer 2 nd and 3 rd 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 Diazepam, other benzos: initial reports that 1 st 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:?

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 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-contcont 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 1 st 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-contcont If stability requires 1 st 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 1 st trimester, discuss ultrasound examination of the fetus at 16-1818 wks of pregnancy and how malformations might be handled (abortion?) before conception.

Managing Pregnancy in Women Who Require Chronic Psychotropics-contcont To diminish the period off of or on less than optimal medication, resuming most psychotropics after the 1 st 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.