Disclosures. Objectives. Talk Overview 11/28/2016. Medication for Women in the Perinatal Timeframe: Safe and Effective Pharmacology

Transcription

1 Medication for Women in the Perinatal Timeframe: Safe and Effective Pharmacology Disclosures Legal consultant to Astra Zeneca, Eli Lilly, Johnson and Johnson Research Support from NIMH, Stanley Medical Research Foundation, SAGE Jennifer L. Payne, M.D. Director, Women s Mood Disorders Center Johns Hopkins School of Medicine Off label uses of medications will be discussed throughout this presentation Objectives Participants will be able to: Name one infant outcome associated with in utero antidepressant exposure and the rate of this outcome Identify a medication that can be used safely during pregnancy as an alternative to benzodiazepines Talk Overview General Rules for Medication Management During Pregnancy Antidepressants: A Review of the Risks Evidence based treatment of Postpartum Depression 1

2 General Rules for Medication Plans During Pregnancy The Rules- Planning for Pregnancy Assume all women of reproductive age will get pregnant! Consider Exposure to Psychiatric Illness In Utero an Exposure for the Baby Limit the number of exposures for the baby Use medications that we know more about Every case is different! It s a Team Sport Category B is NOT necessarily safer than Categories C and D! Category B Animal studies have revealed no evidence of harm to the fetus, however, there are no adequate and well-controlled studies in pregnant women OR Animal studies have shown an adverse effect, but adequate and well-controlled studies in pregnant women have failed to demonstrate a risk to the fetus. New meds typically are rated Category B 2

3 The Rules: OOPS See or talk to the patient ASAP Don t stop all meds immediately- most psychiatric meds can be continued Taper meds when possible Consider the risks of stopping teratogenic meds and educate everybody Try to minimize the number of meds If the patient is ill, make a plan that includes treating the illness. Antidepressants in Pregnancy: Risks That Have Been Studied Spontaneous Abortion Preterm Birth and Birth Weight Heart Defects Persistent Pulmonary Hypertension Poor Neonatal Adaptation Syndrome Autism Problems with the Literature Most studies don t control for: The underlying psychiatric illness Severity of psychiatric illness Risk factors that are found in a higher rate in the psychiatric population Diabetes, Smoking, Substance Use, Obesity etc Whether or not the mother was psychiatrically ill during pregnancy Multiple medications 3

4 Heart Defects Risk of Cardiac Malformation in Infants, According to Maternal Exposure to Antidepressants. Multiple studies- some positive, some negative Most recent and largest: Huybrechts KF (N Engl J Med 2014;370: ) Over 900K sample Controlled for MDD and severity of MDD No association with heart defects in the adjusted analyses Huybrechts KF et al. N Engl J Med 2014;370: Included population based cohort studies of SSRI s during pregnancy 4 cohort studies: 1,996,519 participants Compared women with MDD who took SSRIs to women with MDD who did not take antidepressants (i.e. controlled for MDD) OR 1.06 ( )-Not significant Wang et al, J Amer Heart Assoc, 2013 Paxil? 4

5 Persistent Pulmonary Hypertension (PPHN) PPHN failure of pulmonary vascular resistance to decrease at birth 1-2 per 1000 live births Associated with: Maternal smoking, maternal diabetes, meconium aspiration, postmarturity, C-section, sepsis, others Leads to substantial infant mortality (10-20%) and morbidity Perspective on PPHN 1-2 infants in the general population normally develop PPHN If the odds ratio is 6 (the highest found) 6-12 infants per 1000 exposed to SSRIs in late pregnancy will develop PPHN Approximately 99% of infants exposed will NOT develop PPHN Autism Several studies have found an increased risk of autism in children with in utero antidepressant exposure Others have not found an increased riskparticularly those that have specifically controlled for psychiatric illness Results: Berard et al (JAMA Pedicatrics) AD use during the second and/or third trimester of pregnancy was statistically significantly associated with an 87% increased risk of ASD, after taking all potential confounders into account. N=31, Increased risk from 0.7% to 1.3% The effect was persistent even after taking into account maternal history of depression (adjusted hazard ratio, 1.75; 95% CI, ). Note: close to 1 In sensitivity analysis restricted to children with a diagnosis of ASD confirmed by specialists (psychiatrists and/or neurologists), the findings were consistent with those of the main analyses, increasing the validity of these results. But these results were not statistically significant 5

6 Poor Neonatal Adaptation Syndrome Cluster of symptoms seen in 20-30% of infants exposed to SSRI s during the 3 rd trimester Also seen in infants exposed to tricyclics, other meds and no meds Unclear if due to withdrawal or toxicity Symptoms include: respiratory distress, temperature changes, feeding difficulty, jitteriness, irritability, fits, difficulty settling, floppiness, rigidity, hypoglycemia, and jaundice No blinded studies conducted to date examining whether these symptoms are more common in SSRI (or other AD) exposed infants or not Frequencies of Specific Signs Reported to the FDA Adverse Events Reporting System30 Moses-Kolko, E. L. et al. JAMA 2005;293: Copyright restrictions may apply. Poor Neonatal Adaptation Syndrome: Issues to be Explored Clear definition Measurement Blinded studies in both exposed and unexposed infants, including maternal psychiatric illness as a variable Does tapering of SSRI in 3 rd trimester decrease the rate? Does this increase the risk of PPD? Does breastfeeding impact severity or rate? Recent study suggested formula feeding increases the risk Are there long-term repercussions of the syndrome? General Recommendations: Antidepressants SSRI s and SNRI s generally considered safe Consider tricyclics (blood levels) Of the SSRIs Zoloft and Prozac have the most evidence for safety Paxil has been associated with heart defects in some studies with exposure in the 1 st trimester Less evidence for others including Wellbutrin which until recently was FDA category B Risk for Persistent Pulmonary Hypertension extremely small 6

7 Management of Antidepressants during Pregnancy FDA recommends tapering antidepressants during the third trimester No definition of tapering- 50%? 100%? Not clear when No study supports this as a safe practice No study supports this practice as decreasing infant risks Clinically rarely done Management of Antidepressants during Pregnancy We know that antidepressant blood levels decrease across the course of pregnancy Many cases of PPD actually begin during the 3 rd trimester Blood levels, when feasible should be monitored Currently we recommend managing by clinical presentation Treatment of Anxiety in Pregnancy Benzodiazepines Early evidence for association with cleft palate, now not entirely clear Associated with preterm birth, low birth weight Floppy baby syndrome and withdrawal if large doses used in 3 rd trimester Gabapentin Fairly extensive seizure literature indicates no increased risk of teratogenicity (Use folic acid!) Breastfeeding 7

8 Breast Feeding: Rule Number 1 All psychiatric medications enter breast milk Breast Feeding Rule Number 2 If the baby was exposed in utero there is usually no reason to not continue the medication during breast feeding Exceptions: clozaril or if baby seems to be sedated or having particular side effects Lithium toxicity has occurred in infantsmonitor blood levels, TSH and kidney function If mom is not doing well on a medication used during pregnancy- switch to another! Antidepressants Generally considered safe in breastfeeding Recommendations for Breast Feeding Take medication right after baby feeds and right before the longest time baby sleeps Pump and dump for the next feeding- Note no evidence for this and may agitate anxious patients! Monitor blood levels in the baby when appropriate Involve the pediatrician 8

9 Evidence Based Treatment of Postpartum Depression Postpartum Mood Disorders: Three Syndromes The Blues Postpartum Depression Postpartum Psychosis Postpartum Blues Occur 1-10 days postpartum Lasts 2-3 days, must be less than 2 weeks Symptoms: mild mood lability, tearfulness, irritability Occurs after up to 80% of deliveries May be considered normal Unrelated to psychiatric history Postpartum Depression Symptoms meet criteria for a Major Depressive Episode. May start during pregnancy and continue postpartum DSM-IV criteria: Symptoms begin within ONE month DSM-5 Now uses Peripartum 9

10 How Common is Postpartum Depression? Depends on the population! Many postpartum depressions begin during pregnancy so rates are not completely clear General Population: 13-17% when assessed postpartum only (so includes cases that start during pregnancy) Most go on to have recurrent MDD In women with pre-existing MDD and Bipolar Disorder: around 20-30% with symptom onset postpartum around 50% when including symptoms during pregnancy and postpartum Risk Factors for Postpartum Depression History of Major Depression, Bipolar disorder or other psychiatric illness Previous Postpartum Depression Family History of Postpartum Illness History of severe PMS or PMDD Stress Poor social support Marital discord PPD versus the Blues PPD is more likely than the Blues if There is a history of a Mood Disorder Symptoms are severe Symptoms are unusual Suicidal thoughts Thoughts of harming the baby Psychotic symptoms There is functional impairment Symptoms last longer that 2-3 days Questions to Ask Functioning at home, work, self and baby care Thoughts of suicide Thoughts of harming the baby Personal or family history of bipolar disorder Intrusive, obsessive thoughts 10

11 Edinburgh Postnatal Depression Scale Guidelines for Treating Postpartum Depression Prevention in Women at High Risk Make a plan prior to pregnancy if possible Education Close follow-up Medication: Highest risk in women off of medications who have a history of a mood disorder Decreased risk with use of medications during pregnancy If the patient is off of medications, should restart immediately postpartum Rule 1: Educate, Educate, Educate Include information about Major Depression, Bipolar Disorder and Suicidal Thoughts Educate the patient and everybody else associated with the patient (husband, mother, etc) If starting a medication and the patient is breastfeeding, discuss with the pediatrician 11

12 Education: Risk for Bipolar Disorder In first episode PPD (no previous history of mood disorder) should: Screen for personal history of hypomanic/manic episodes Screen for family history of bipolar disorder** Specifically educate about hypomanic and manic symptoms Rule 2: Check for Suicidal Thoughts Risk for suicide deaths and attempts is lower during and after pregnancy than in the general population BUT suicide accounts for up to 20% of all postpartum deaths AND suicide represents one of the leading causes of peripartum mortality Make a safety plan Rule 3: Check for Thoughts of Harming the Baby Directly ask, note that these thoughts are common Don t morally condemn the thoughts 3 Kinds Obsessive anxious thoughts or Obsessions Actual thoughts of harm without intent Thoughts of harm with intent Also assess for symptoms that would increase the likelihood of the woman acting on the thoughts Psychotic symptoms Suicidal thoughts Poor social support/chaos Obsessions vs Obsessive Anxious Thoughts Very common Ego-Dystonic If true obsessions may be accompanied by compulsions Obsessive Anxious thoughts are less specific then true obsessions and the focus of them changes- What if? Increases anxiety and agitation Note that the woman may be very ashamed 12

13 Rule 4: Close Follow-Up Monitor for suicidal thoughts Monitor for thoughts of harming the baby Monitor for emerging bipolar disorder symptoms Provide support and further education Weekly visits are best until it s clear that things are stabilizing Rule 5: Find Support for the Patient Postpartum Support Groups Online Support Groups Play Groups for New Moms Books on Postpartum Depression CBT To Treat or Not to Treat? All psychiatric medications enter breast milk To date there do not appear to be clear longterm effects in children exposed to antidepressants in breast milk Children of depressed mothers have slower development, more behavioral and psychological problems and lower IQ Suicide accounts for up to 20% of all postpartum deaths Treatment of Postpartum Depression: Antidepressants Very few studies Several Open-Label 2 randomized trials in prevention 1 randomized trial in treatment SSRI s may be more efficacious and/or rapid 13

14 Wisner et al 2001 Nortriptyline did not separate from placebo in preventing recurrent PPD 51 women with a history of PPD 26 women were randomly assigned to Nortriptyline and 25 to placebo 6 relapsed in each group over 20 weeks postpartum Nortriptyline may not have been optimally dosed Wisner et al, 2004 Sertraline was superior to placebo in preventing recurrent PPD 22 women with a previous PPD Double-blind, randomized 14 received sertraline 8 received placebo 1 on sertraline developed a MDE 4 on placebo developed a MDE 2 others developed a MDE when sertraline was tapered and withdrawn Wisner, et al 2004 Wisner et al, 2006 Treatment of PPD 109 women with PPD (within 3 months of delivery) were randomized (double-blind) to either sertraline or nortriptyline Sertraline and nortriptyline had equal efficacy in the treatment of current PPD but the response to sertraline was significant within the first week of treatment, while the response to nortriptyline was not significant until week 2. 14

15 Case Study 1 Case Studies Remember: Every case is different and there are no absolute right or wrong answers!!! Susan is taking vilazodone and has been well for the last year She has a history of hospitalization for a suicide attempt before starting vilazodone She s never tried other antidepressants She wants to become pregnant- what shall we do? Case Study 1-Version 2 Susan is taking vilazodone and has been well for the last year She has a history of hospitalization for a suicide attempt before starting vilazodone She s never tried other antidepressants She just found out that she s pregnantwhat shall we do? Case 2 Lucy presents 4 weeks after delivery with low mood, crying spells, inability to sleep even when the baby is sleeping, anxiety and a PDW. Lucy has a history of depression but did not respond to SSRI s. She is breastfeeding. 15

16 Case 3 Cynthia presents 28 weeks pregnantshe s always been anxious at baseline but is now having intrusive thoughts that many things around her (the paint, fumes, what she eats) can cause harm to her baby. She s having crying spells and feels paralyzed. She reports panic attacks on a daily basis and has not been able to go to work. Case 4 Amanda is a 28 year old female who wants to get pregnant in the next year. She takes Prozac 80mg, Ativan 1mg daily and Ritalin 20mg BID for major depression, trouble sleeping and a history of ADHD. She smokes 1 pack per day. Recommendations? Case 5 Goal: Healthy Mom, Healthy Baby! Samantha has a history of Major Depression but went off medications for pregnancy. She has a relapse postpartum and meets criteria for a major depressive episode. She s breast feeding. She s also very anxious and cannot sleep. 16