Psychiatric Illness in the Perinatal and Postnatal Patient

1. Psychiatric Illness in the Perinatal and Postnatal Patient Jillian Glass, MD April 8, 2011

2. No financial relationship with any pharmaceutical company

3. 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

4. Myths • Pregnancy is protective against psychiatric illness • Pregnancy is “naturally happy” time in life

5. 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

6. Complications of Diagnosis • Overlap in symptoms of “normal” pregnancy and major depression • Changes in appetite • Changes in sleep • Fatigue • Problems with concentration

7. Most Common Symptoms in Antenatal or Postpartum Depression • Sadness • Anxiety/Panic Attacks • Feelings of Guilt and Hopelessness • Insomnia • Thoughts of harming self or baby

8. 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

9. Risk Factors • Social • Poor support • Marital or family discord • Low socioeconomic status • Recent stressful events • Unplanned or unwanted pregnancy

10. 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

11. Treatment Options • Education • Support • Psychotherapy • Medication • ECT

12. The Medication Dilemma Expose the mother to risks of psychiatric illness ? or Expose the fetus to side effects of medication ? or BOTH ?

13. 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

14. 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

15. Effects of Untreated Depression • 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

16. Postpartum Effects on Mother • Increased likelihoood of postpartum depression • Occurs 4 wks to 6 mos postpartum, 10-20% incidence • Postpartum psychosis • 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

17. Other postpartum effects • 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

18. 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

19. Fetal and Neonatal Antidepressant Side Effects • Respiratory Distress • Jitteriness • Tremor • Decreased muscle tone • Withdrawal effects • Sleep problems • Hypoglycemia • Rare Seizures, arrhythmias

20. 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

21. 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)

22. 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

23. 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

24. 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 noassociation between the use of paroxetine in pregnancy and riskof cardiovascular defects in exposed infants

25. Antidepressants - SSRIs • Citalopram • No increased risk of malformations in 1 prospective, controled study and in large registry data base • Escitalopram • Not systematically studied

26. 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

27. 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

28. 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

29. Other Psychiatric Ilnesses • Generalized Anxiety Disorder: Excessive worry and difficulty controlling the worry • 3 of the following: • Irritability • Insomnia • Fatigue • Restlessness • Muscle Tension

30. Other Psychiatric Illnesses • Panic Attacks • Sudden onset episode of intense fear or discomfort that typically peaks at 10 minutes • Physical symptoms (4/13) • 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

31. 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: • 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)

32. 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%

33. 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

34. 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

35. 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

36. 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

37. 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

38. 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

39. 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

40. 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

41. 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.

42. 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).

43. Resources • ACOG Practice Bulletin • Clinical Management Guidelines for OB/GYNs • Number 92, April 2008 • Perinatal Mood Disorders: Components of Care Program 2009