Treating Depression During Pregnancy with Selective

Serotonin Reuptake Inhibitors

Master’s Project 646

Jenny Collins

Introduction

■Peak prevalence of depression in women occurs between ages 25 and 45, which includes the childbearing years

■One in four women will experience depression during pregnancy

■Most agree that all types of medication should be avoided during pregnancy

Symptoms of Depression

■Sleep disturbances

■Lack of interest

■Feelings of guilt

■Loss of energy

■Difficulty concentrating

■Changes in appetite

■Suicidal thoughts or ideations

Untreated Depression During Pregnancy

■Miscarriage

■Babies born at an early gestational age

■Low birth weight

■Increased risk of preeclampsia

■Low neonatal Apgar scores

■Increased admissions to neonatal ICUs

■Postpartum depression--most serious

Drug Discontinuation During Pregnancy

■Discontinuation may lead to serious relapses

■Sample of 201 women showed that 43 percent experienced a relapse of major depression during pregnancy

■Exposure of a fetus to maternal depression may be as toxic as exposure to antidepressants

Treatment Options■Behavioral therapy--First Line

■Support groups

■Counseling

■Psychotherapy

■Individual

■Group

■Family

■Pharmacotherapy■TCA’s

■SSRI’s--used most often, due to less side affects and most studied

■Note: No psychiatric medication has been endorsed by the FDA for use during pregnancy

■The decision to place a pregnant patient on an SSRI is based on clinical judgment and the latest research

SSRI Exposure During Pregnancy

■Most common■Fluoxetine (1st developed)

■Sertraline

■Fluvoxamine

■Most SSRIs fit under the Category C on the pregnancy-risk factors

■However, Paroxetine was relabeled in 2005 to a Category D (positive evidence of fetal risk)

■Maternal use of SSRIs in late pregnancy may be a risk factor for Persistent Pulmonary Hypertension (PPHN) of the newborn

■Neonatal Withdrawal

Neonatal Withdrawal

■Symptoms○Difficulty breathing○Jitteriness○Increased muscle tone○Irritability○Altered sleep patterns○Tremors○Difficulty feeding

■Baby should stay in a special care nursery for several days until the withdrawal symptoms go away

What is Persistent Pulmonary Hypertension?

■10-20% of all affected infants will not survive

■Present shortly after birth with severe respiratory failure requiring intubation and mechanical ventilation

SSRIs Linked to PPHN?

■Remember: PPHN results from increased pulmonary vascular resistance

■Serotonin:■Vasoconstrictive properties■Inhibits nitric oxide (vasodilator)

■Bottom Line: Women taking SSRIs in the second half of pregnancy will see their baseline risk of having a child with PPHN increase from 0.1% to 0.6%.

■The study was too small to compare the risk in one drug compared to another

Guidelines for SSRI Use During Pregnancy

■Only in cases of moderate to severe depression■Use the minimum effective dosage needed to

maintain psychiatric stability and normal functioning■History of recurrent episodes of depression

predisposes women to relapse during pregnancy■Paroxetine use among pregnant women and

women planning pregnancy should be avoided■Taper SSRIs during late pregnancy as gradually

as possible and over several weeks (needs more research)

Future Research

■Undertake larger studies

■Control for trimester and length of exposure

■Control for dosage and type of SSRI used

■Children after they are born?

■Determine the benefits/risks of tapering SSRIs during late pregnancy

Conclusion■Remember this is a unique population

■Recognize that depression is common in women of childbearing age

■There is a serious risk of relapse of depression when SSRIs are discontinued

■Decisions regarding treatment should always be individualized and based on nature and severity of current and past symptoms of mood instability

■Paroxetine (Paxil) use in pregnancy or in women planning to become pregnant should be avoided

■Be on the look out for those neonatal withdrawal symptoms

ReferencesACOG Committee Opinion: Treatment With Selective Serotonin Reuptake Inhibitors During Pregnancy. Ob Gyn 2006; 108:1601-1603.Barclay L., Prenatal Exposure to SSRIs Linked to Low Birth Weight, Respiratory Distress. Medscape Medical News, 2006.Bennett H., Einarson A., Taddio A., Koren G., Einarson T. Prevalence of depression during pregnancy: systematic review. Obstetrics and Gynecology 2004; 103:698-709.Bodnar L., Sunder K., Wisner K. Treatment with selective serotonin reuptake inhibitors during pregnancy: deceleration of weight gain because of depression or drug? Am J Psychiatry 2006; 163(6):986-991.Bonari L., Pinto N., Ahn E., Einarson A., Steiner M., Koren G. Perinatal risks of untreated depression during pregnancy. Can J Psychiatry 2004; 49:726-735.Burt, V. Major Depression During Pregnancy: Implications of Illness and Treatment Considerations. Women's Health in Primary Care 2007; Feb.: 28-37.Chambers C., Johnson K., Dick L., Felix R., Jones K. Birth outcomes in pregnant women taking fluoxetine. NEJM 1996; 335:1010-1015.Cohen L., Altshuler L., Harlow B., Nonacs R., Newport J., Viguera A., et al. Relapse of major depression during pregnancy in women who maintain or discontinue antidepressant treatment. JAMA 2006; 295:499-507.Dolan S. Medication exposure during pregnancy: antidepressants. Medscape Ob/Gyn & Women's Health 2005; 10(1).Einarson A., Selby P., Gideon K. Abrupt discontinuation of psychotropic drugs during pregnancy: fear of teratogenic risk and impact of counseling. J Psychiatry Neurosci 2001; 26:44-48.Epperson C., G. Anderson, C. McDougle. Sertraline and breastfeeding. N Engl J Med 1997; 336:1189-1190.Kalra S., Einarson A., Koren G. Taking antidepressants during late pregnancy. Canadian Family Physician 2005; 51:1077-1078.Kent L. and J. Laidlaw. Suspected Congenital Sertraline Dependence. Br J Psychiatry 1995; 167:412-413.Koren G., Matsui D., Einarson A., Knoppert D., Steiner M. Is maternal use of selective serotonin reuptake inhibitors in the third trimester of pregnancy harmful to neonates? CMAJ 2005; 172:1457-1459.Laine K., Heikkinen T., Ekblad U., Kero P. Effects of exposure to selective serotonin reuptake inhibitors during pregnancy on serotonergic symptoms in newborns and cord blood monoamine and prolactin concentrations. Arch Gen Psychiatry 2003; 60:720-726.

Lavenstein B., Latimer E., Smith Y., Baker R. Neonatal fluoxetine withdrawal syndrome-a movement disorder secondary to maternal use during pregnancy. Neuropediatrics 2006; 37.

Marcus S., Flynn H., Blow F., Barry K. Depressive symptoms among pregnant women screened in obstetrics settings. J Womens Health 2003; 12:373-380.

MayoClinic.com

Mills J. Depressing observations on the use of selective serotonin-reuptake inhibitors during pregnancy. N Engl J Med 2006; 354:636-638.

Misri S., Burgmann A., Kostaras D. Are SSRIs safe for pregnant and breastfeeding women? Can Fam Physician 2000; 46:626-633.

Nordeng H., R. Lindemann, K. Perminov, A. Reikvam. Neonatal withdrawal syndrome after in utero exposure to selective serotonin reuptake inhibitors. Taylor & Francis 2001; 90:289-291.

Phend C. Not treating depression during pregnancy affects. Medpage Today 2006.

Reinberg, S. Maternal Antidepressant Use Can Trigger Withdrawal in Newborns. HealthDay News 2007.

Stack C. Pharmacotherapy update from the department of pharmacy. The General Use of Medications in Pregnancy 1999; 2.

Wikipedia Encyclopedia.

Wisner K., Zarin D., Appelbaum P., Gelenberg A., Leonard H., Frank E. Risk-benefit decision making for treatment of depression during pregnancy. Am J Psychiatry 2000;157:1933-1940.

www.fda.gov

Zeskind P., Stephens L. Maternal selective serotonin reuptake inhibitor use during pregnancy and newborn neurobehavior. Pediatrics 2004; 113:368-375.

Questions?