TREATING THE MOTHER PROTECTING THE UNBORN A MOTHERISK Educational Program The content of this program reflects the expression of a consensus on emerging clinical and scientific advances as of the date issued and may be subject to change. The information should not be construed as dictating an exclusive course of treatment or procedure to be followed. Case Study 1 You have read a warning from FDA and Health Canada about the use of SSRIs and a risk for cardiac malformations and withdrawal syndrome You are not sure what to do with your pregnant depressed patients Case Study 2 A pregnant women is on lithium for bipolar disorder Discovered pregnancy at 10 weeks GA Afraid to continue lithium due to fear of cardiac malformations What should you do? 1
Diagnosis and Etiology Peak onset during childbearing age Etiology unknown, but depression is associated with: Substance abuse or dependence involving CNS depressants (alcohol) or CNS stimulants (cocaine) Other drug therapy, such as antihypertensives, norepinephrine, serotonin or dopamine antagonists Chronic diseases including malignancies MDE-1 Prevalence of 10 to 16% of pregnant women fulfill the DSM-IV criteria 10% meet criteria for drug therapy 50% rate of recurrence following a single episode 50 to 62% will have another postpartum episode 15% attempt suicide MDE-1, 2 Impact of Depression on Pregnancy Often neglected in research Prematurity Low birth weight Physiological and emotional withdrawal Predictor of postpartum depression 2
Impact of Pregnancy on Depression High relapse rate of pregnant depressed women who discontinue their therapy Among women discontinuing abruptly their antidepressants: 94% discontinued abruptly for fear of teratogenicity 77.7% did so on their physician s advice Following discontinuation: 70.3% had physical and psychological adverse effects 29.7% had suicidal ideation 10.8% were admitted to hospital MDE-3, 4 Clinical Considerations As late as 1988, physicians were advised to avoid pharmacological treatment during pregnancy By 1998, major antidepressants were shown to be safe in pregnancy, and attitudes had changed: Management should be adjusted to the severity of the disease Preconceptional planning should be instituted Treatment should follow benefit/risk assessment MDE-2 Pharmacological Therapy Selective Serotonin Reuptake Inhibitors (fluoxetine, fluvoxamine, paroxetine, sertraline, citalopram) Effective Not associated with a detectable increased risk for major birth defects in 1st trimester Fluoxetine not associated with risk for neurodevelopment Safe in overdose, except citalopram and venlafaxine Abrupt discontinuation may induce withdrawal syndrome in neonates SSRIs are linked to persistent pulmonary hypertension in neonates (1%) Maternal adverse effects: GI problems, sexual dysfunction and serotonin syndrome MDE-5 to 8 3
Tricyclic antidepressants (amitriptyline, nortriptyline, imipramine) Not associated with increased risk for birth defects Not associated with increased risk for neurodevelopment Effective, but with serious maternal adverse effects: cardiotoxicity, severe anticholinergic effects, life-threatening in overdose Poor compliance Monoamine Oxidase Inhibitors (phenelzine, tranylcypromine) Lack of fetal safety data Serotonin and Norepinephrine Reuptake Inhibitors (SNRI) (venlafaxine) Effective Not associated with a detectable increased risk for major birth defects in 1st trimester Maternal adverse effects: GI problems, sexual dysfunction and serotonin syndrome Abrupt discontinuation may induce withdrawal syndrome in neonates Venlafaxine is not shown to affect neurodevelopment of children in utero MDE-9, 10 4
Dopamine and Norepinephrine Reuptake Inhibitors (bupropion) No teratogenicity in one large study Lithium First-line therapeutic option for bipolar disorder Increased risk for: Ebstein s anomaly (low frequency) Neonatal toxicity (hypotonia, hypothyroidism) MDE-11 Neonatal Discontinuation Syndrome from SSRIs When drug is taken at term, 10-20% of babies will experience discontinuation (withdrawal) syndrome Clinical presentation: Irritability, cry, respiratory distress that may lead to need for respiratory support All SSRIs and SNRIs can cause the syndrome Syndrome self limited Should not lead to discontinuation of antidepressant near term Babies born to women taking SSRIs-SNRIs near term should be monitored for 2-3 days. MDE-12 to 14 5