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DEPRESSION DURING PREGNANCY TREATMENT WITH ANTIDEPRESSANTS

DEPRESSION DURING PREGNANCY TREATMENT WITH ANTIDEPRESSANTS. Amanda Tavone , BS c . P harm C andidate , BS c . H on. Outline. Prevalence of Depression in Pregnancy Risk Factors Etiology Impact of Depression Antidepressant Use During Trimesters Impact of Antidepressant Use

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DEPRESSION DURING PREGNANCY TREATMENT WITH ANTIDEPRESSANTS

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  1. DEPRESSION DURING PREGNANCYTREATMENT WITH ANTIDEPRESSANTS Amanda Tavone, BSc. Pharm Candidate, BSc. Hon

  2. Outline Prevalence of Depression in Pregnancy Risk Factors Etiology Impact of Depression Antidepressant Use During Trimesters Impact of Antidepressant Use Approach for Antidepressant Treatment During Pregnancy Example

  3. Aren’t Pregnant Women Usually Happy? Pregnancy traditionally thought to be a time of emotional wellness Current studies show that it is a high risk period for psychiatric illness in females, especially for those who have pre-existing psychiatric disorders De las Cuevas, Carlos and Sanz2, Emilio J. Safety of Selective Serotonin Reuptake Inhibitors in Pregnancy. Current Drug Safety, 2006, 1, 17-24 17

  4. Prevalence of Depression During Pregnancy Rates of mood disorders in women are approximately equal in pregnant and non-childbearing women Prevalence of major depression in pregnant women is between 3.1% to 4.9% Major/minor depressive episodes between 8.5% to 11% Chaudron LH. Complex Challenges in Treating Depression During Pregnancy. Am J Psychiatry 2013; 170: 12-20.

  5. Risk Factors for Depression during Pregnancy • Similar to those for postpartum depression: • History of depression • Lack of social support • Unintended pregnancies • Low socioeconomic status • Domestic violence • Marital status: Single • Anxiety • Stressful life events Chaudron LH. Complex Challenges in Treating Depression During Pregnancy. Am J Psychiatry 2013; 170: 12-20.

  6. Post-Partum Depression • Women with depression while pregnant have an increased risk of postpartum depression • Impact on the health of both mothers and infants Chaudron LH. Complex Challenges in Treating Depression During Pregnancy. Am J Psychiatry 2013; 170: 12-20.

  7. Etiology Hypothesized role of changes in hormone concentrations during pregnancy and the postpartum period Interactions and feedback systems occur between the hypothalamic-pituitary-ovarian (HPO) axis and the hypothalamic-pituitary-adrenal (HPA) axis Evidence is starting to show a link between the HPA axis and psychological stress during pregnancy Chaudron LH. Complex Challenges in Treating Depression During Pregnancy. Am J Psychiatry 2013; 170: 12-20.

  8. Hypothesized Model:Maternal Depression Field, T., Diego, M., Hernandez-Reif, M. Prenatal depression effects on the fetus and newborn: a review Infant behavior & development 29 (2006) 445–455

  9. Depression During Pregnancy Fetus may be directly affected by neurobiological substrates of depression, such as glucocorticoids, which cross the placenta Fetus may be indirectly affected by neuroendocrinemechanisms in which depression modifies physiological maintenance of pregnancy Chaudron LH. Complex Challenges in Treating Depression During Pregnancy. Am J Psychiatry 2013; 170: 12-20.

  10. Impact of Depression During Pregnancy

  11. Impact of Depression During Pregnancy • Poor health behaviours of the mother: • Poor eating • Poor sleep • Subsequent OTC use • Alcohol • Tobacco • Caffeine These may also have affects on the fetus

  12. Impact of Depression on pregnancy, the fetus, and the neonate Few studies have looked specifically on the impact of depression Chaudron LH. Complex Challenges in Treating Depression During Pregnancy. Am J Psychiatry 2013; 170: 12-20.

  13. Impact of Depression • Studies that have focused on depression during pregnancy have shown a correlation with poor obstetrical outcomes including: • Preterm delivery (less than 37 weeks) • Postpartum depression • Neonatal symptoms (i.e. Behaviour) • Higher rates of placental abnormalities • Pre-eclampsia • Spontaneous abortion • Neonates requiring intensive care for postnatal complications Chaudron LH. Complex Challenges in Treating Depression During Pregnancy. Am J Psychiatry 2013; 170: 12-20.Field T, Diego M, Hernandez-Reif. Prenatal depression eeffects on the fetus and newborn: a review. Infant Behavior and Development 29 (2006): 445-455.

  14. Impact of Depression Birth outcomes Neonatal outcomes Maternal outcomes

  15. Impact of Depression Birth Outcomes- Effects on Growth Study of pregnant women compared the effects of untreated depressive symptoms, use of SSRIs, and no depressive symptoms or use of SSRIs Prospective population based study from fetal life onward N=7696 pregnant women included. 7027 pregnant mothers (91.3%) had no or low depressive symptoms, 507 pregnant mothers (7.4%) had clinically relevant depressive symptoms and did not take SSRIs, and 99 pregnant mothers (1.3%) took SSRIs SSRI use was assessed by questionnaires in each trimester and verified by pharmacy record Measures: fetal ultrasonography at each trimester. Fetal body and head growth measured repeatedly Pregnant women who were untreated for depressive symptoms had lower total fetal body growth (-4.4g/wk, 95% CI: -6.3 to -2.4; p<.001) and head growth (-.08mm/wk; 95% CI: -0.14 to -0.03; p=.003) Chaudron LH. Complex Challenges in Treating Depression During Pregnancy. Am J Psychiatry 2013; 170: 12-20. Marroun EH et al. Maternal use of selective serotonin reuptake inhibitors, fetal growth, and risk of adverse birth outcomes. Arch Gen Psychiatry 2012; 69:706-714.

  16. Impact of Depression :Neonatal Outcomes - Behavioural • More than one study showed that depression during pregnancy was correlated withgreater developmental delays in infants • Both of these studies were self-reports of depression • Another study that used more objective assessments for depression did not have the same relationship Chaudron LH. Complex Challenges in Treating Depression During Pregnancy. Am J Psychiatry 2013; 170: 12-20.

  17. Impact of Depression on:Neonatal Outcomes- Behavioural Increased risk for irritability Decreased activity and attentiveness Fewer facial expressions Their negative effects continues into later infancy and their cortisol responses to mild stress can cause negative effect when toddlers. Infants have been shown to have inferior mental, motor and emotional development, and later social and emotional problems during childhood. Chaudron LH. Complex Challenges in Treating Depression During Pregnancy. Am J Psychiatry 2013; 170: 12-20.Field T, Diego M, Hernandez-Reif M: Prenatal depression effects on the fetus and newborn: a review. Infant Behav Dev 2006; 29: 445-455.

  18. Impact of Depression During Pregnancy on the Mother Vegetative symptoms Self-harm Suicide Psychosis Depression and anxiety in early pregnancy linked to pre-eclampsia? Chaudron LH. Complex Challenges in Treating Depression During Pregnancy. Am J Psychiatry 2013; 170: 12-20. Kurki et al. Depression and anxiety in early pregnancy and risk for pre-eclampsia. ObstetGynecol 2000; 95: 487-490.

  19. Antidepressant Treatment During Pregnancy

  20. Treatment with Antidepressants Majority of women with depression do not obtain treatment during pregnancy Chaudron LH. Complex Challenges in Treating Depression During Pregnancy. Am J Psychiatry 2013; 170: 12-20.

  21. Antidepressant Use in Pregnancy Concern: all psychotropic medications pass through the placenta Use of antidepressants during pregnancy has increased. This is also due to the overall increase in SSRI use. In pregnant women SSRIs are most frequently prescribed, then SNRIs, TCAs, and rarely, monoamine oxidase inhibitors (similar to general population) Chaudron LH. Complex Challenges in Treating Depression During Pregnancy. Am J Psychiatry 2013; 170: 12-20.

  22. Antidepressant Use During Pregnancy Rates of use during pregnancy are highest during the first trimester Antidepressant use decreases from the first to the second to the third trimester Rates of use during pregnancy are somewhat lower than those who take them before or after pregnancy. Chaudron LH. Complex Challenges in Treating Depression During Pregnancy. Am J Psychiatry 2013; 170: 12-20.

  23. Antidepressant Use During Pregnancy Declining trend of antidepressant use throughout pregnancy terms may be due to third-trimester exposure and poor neo-natal adaptation syndrome Treatment is usually inadequate during pregnancy; lower doses are taken. May be due to concern from patient and provider about a dose-dependent correlation between exposure and obstetrical and neonatal outcomes (not supported by evidence) Chaudron LH. Complex Challenges in Treating Depression During Pregnancy. Am J Psychiatry 2013; 170: 12-20.

  24. Antidepressant Use During Pregnancy Stopping antidepressants during pregnancy, puts women at a higher risk for recurrence of depression. Chaudron LH. Complex Challenges in Treating Depression During Pregnancy. Am J Psychiatry 2013; 170: 12-20.

  25. Antidepressant Use During Pregnancy Cohen LS et al. Relapse of major depression during pregnancy in women who maintain or discontinue antidepressant treatment. JAMA 2006; 295: 499-507. Prospective study analysis determined time to relapse of depression during pregnancy. n= 201 Result: Women who discontinuedmedicationrelapsedsignificantly more frequently over the course of their pregnancy compared to women who continued taking their medication. HR, 5.0; 95% CI, 2.8-9.1 p<.001

  26. Impact of Antidepressants During Pregnancy

  27. Impact of Antidepressant Use During Pregnancy Pregnancy loss Growth reduction (reduced head growth, low birth weight, small for gestational age) Preterm birth Malformations Neonatal adaption Slower neonatal and infant motor development Persistent pulmonary hypertension Infant and child behavioural effects Mother’s health Chaudron LH. Complex Challenges in Treating Depression During Pregnancy. Am J Psychiatry 2013; 170: 12-20.

  28. Impact of Antidepressant Use During Pregnancy Not all studies have shown associations between antidepressant use and outcomes Difficult to determine cause and effect, since there are confounding factors, such as substance use, co-morbid conditions (i.e. anxiety) , socioeconomic status, ethnicity, prenatal anger, combined optimism and pessimism Chaudron LH. Complex Challenges in Treating Depression During Pregnancy. Am J Psychiatry 2013; 170: 12-20. Field et al. Prenatal Depression effects on the fetus and newborn: a review. Infant Behavior and Development 29 (2006): 445-455.

  29. Birth Outcomes • Taking a look at: • Miscarriage • Effects on growth • Malformations • Birth weight • Gestational Age • Preterm delivery

  30. Miscarriage Increased risk with use in early pregnancy 12.4% (10.8%-14.1%, n=1534) vs 8.7% (7.5% to 9.9%; n = 2033) Objective of study: determine baseline rates of spontaneous abortions and whether antidepressants increased those rates 6 cohort studies of 3567 women (1534 exposed, 2033 unexposed). Matched on important confounders Authors concluded that depression itself cannot be ruled out Hemels ME, Einarson A, Koren G, Lanctot KL, Einarson TR. Antidepressant use during pregnancy and the rates of spontaneous abortions: a meta-analysis. Ann Pharmacother. 2005 May;39(5):803-9.

  31. Effects on Growth Prospective population-based study from fetal life onward 7696 pregnant women included in study: 570 pregnant mothers (7.4%) had clinically relevant depressive symptoms and used no SSRIs, and 99 pregnant mothers (1.3%) used SSRIs SSRI use assessed by questionnaires in each trimester and verified by pharmacy records Fetal ultrasonography done at each trimester Reduced fetal head growth in mothers who used SSRIs (-0.18mm/wk, 95% CI: -0.32 to -0.07, p= .003) Higher risk for preterm birth (not statistically significant) Marroun EH,  et al. Maternal use of selective serotonin reuptake inhibitors, fetal growth, and risk of adverse birth outcomes. Arch Gen Psychiatry. 2012 Jul;69(7):706-14. .

  32. Malformations Structural Malformations • No association between SNRI use • Conflicting data for TCA use • Conflicting data for SSRI use (specifically paroxetine) Cardiac Malformations • No increase in rate with SSRI use (4 studies) • Increase risk in first trimester exposure to paroxetine (three studies). Not found in three other studies • Combination of SSRI and benzodiazepine may increase congenital heart defects Chaudron LH. Complex Challenges in Treating Depression During Pregnancy. Am J Psychiatry 2013; 170: 12-20

  33. Low Birth Weight Increased risk with SSRI or TCA use Chaudron LH. Complex Challenges in Treating Depression During Pregnancy. Am J Psychiatry 2013; 170: 12-20

  34. Small for Gestational Age Small increased risk with SSRI use compared with depressed mothers who did not take SSRIs Chaudron LH. Complex Challenges in Treating Depression During Pregnancy. Am J Psychiatry 2013; 170: 12-20

  35. Preterm Delivery Inconclusive relation Some studies found an increased risk, others did not More exposure, more likely to decrease gestational age Chaudron LH. Complex Challenges in Treating Depression During Pregnancy. Am J Psychiatry 2013; 170: 12-20

  36. Neonatal Outcomes Behavioural Persistent Pulmonary Hypertension Long term growth, IQ, Behavioural

  37. Neonatal Outcomes • Behavioural • Increase in risk for irritability, jitteriness, seizures in mothers who took TCAs • Increase in risk for irritability, tachypnea, hypoglycemia, weak/absent cry and seizures in mothers who took SSRIs in late pregnancy • Persistent pulmonary hypertension • Conflicting data Chaudron LH. Complex Challenges in Treating Depression During Pregnancy. Am J Psychiatry 2013; 170: 12-20

  38. Neonatal Outcomes Continued • Long term growth, IQ, behavioural • Limited Information • Most studies how no relationship with use of SSRIs or TCAs • Slower in reaching developmental milestones but “catch up” by 19 months • Possibility of increased risk to autism spectrum disorder? • IQ, language, development- no difference Chaudron LH. Complex Challenges in Treating Depression During Pregnancy. Am J Psychiatry 2013; 170: 12-20

  39. Maternal Outcomes • Pregnancy-induced hypertension, pre-eclampsia, and eclampsia • Increased risk by approximately 50% • Limitations in studies: linked databases, control for depression and confounding risk factors, mother’s report of antidepressant use Chaudron LH. Complex Challenges in Treating Depression During Pregnancy. Am J Psychiatry 2013; 170: 12-20

  40. Approach and Strategies TREATING DEPRESSED PREGNANT WOMEN

  41. General Approach to Treating Depression During Pregnancy Obtain thorough history Meet with patient to review risk and benefits at trimesters of pregnancy Inter-professional collaboration with obstetrician, pediatrician, and psychiatrist Identify triggers: have a plan if dose change needed Encourage healthy lifestyle Know limitations of studies “Big Picture” Approach Chaudron LH. Complex Challenges in Treating Depression During Pregnancy. Am J Psychiatry 2013; 170: 12-20

  42. When Should We Be Giving Antidepressants to a Pregnant Patient? After thorough evaluation Major Depression Mild-Moderate depression: psychosocial supports, modify stressors Treating depression during pregnancy can be difficult; no safe answer Not treating depression can have serious consequences Chaudron LH. Complex Challenges in Treating Depression During Pregnancy. Am J Psychiatry 2013; 170: 12-20

  43. Strategies for Using Antidepressants in Pregnancy Monotherapy, if possible Avoid first trimester exposure Avoid first trimester antidepressant and benzodiazepine combinations Continue using antidepressants if depression is severe Taper dose, do not stop suddenly Treat to remission Use lowest effective dose Chaudron LH. Complex Challenges in Treating Depression During Pregnancy. Am J Psychiatry 2013; 170: 12-20

  44. Non-Pharmacological Measures Psychotherapy alone or in combination with antidepressants Individual/group therapies Bright light therapy ECT (reserved for severe depression) No reports of impact on fetal, neonatal, or birth outcomes Chaudron LH. Complex Challenges in Treating Depression During Pregnancy. Am J Psychiatry 2013; 170: 12-20

  45. Topics to be Discussed at Each Trimester

  46. First Trimester Exposure • Known and unknown risks for: • Specific malformations • Pregnancy loss or miscarriage Chaudron LH. Complex Challenges in Treating Depression During Pregnancy. Am J Psychiatry 2013; 170: 12-20

  47. Second Trimester Exposure • Effects on: • Fetal growth • Birth weight • Size for gestational age Chaudron LH. Complex Challenges in Treating Depression During Pregnancy. Am J Psychiatry 2013; 170: 12-20

  48. Third Trimester Exposure • Effects on: • Birth weight • Size for gestational age • Risks for: • Persistent pulmonary hypertension • Neonatal adaptation syndrome Chaudron LH. Complex Challenges in Treating Depression During Pregnancy. Am J Psychiatry 2013; 170: 12-20

  49. For The Clinician Check out my website: depressionduringpregnancy.weebly.com

  50. Read More • Website for the clinician contains: • Pamphlet/Resource for your patients • Summary/review • Critical appraisal of literature • This presentation • Cited three review articles on depression and antidepressant use during pregnancy

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