depression during pregnancy treatment with antidepressants

AMANDA TAVONE, BS C . P H A R M C A N D I D AT E , BS C . H O N

DEPRESSION DURING PREGNANCYTREATMENT WITH ANTIDEPRESSANTS

Outline

Prevalence of Depression in PregnancyRisk FactorsEtiologyImpact of DepressionAntidepressant Use During TrimestersImpact of Antidepressant UseApproach for Antidepressant Treatment

During PregnancyExample

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

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.

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


Post-Partum Depression

Women with depression while pregnant have an increased risk of postpartum depression

Impact on the health of both mothers and infants


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


Hypothesized Model:Maternal Depression

Field, T., Diego, M., Hernandez-Reif, M. Prenatal depression effects on the fetus and newborn: a reviewInfant behavior & development 29 (2006) 445–455

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 neuroendocrine mechanisms in which depression modifies physiological maintenance of pregnancy


Impact of Depression During Pregnancy

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

Impact of Depression on pregnancy, the fetus, and the neonate

Few studies have looked specifically on the impact of depression


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

complicationsChaudron 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.

Impact of Depression

Birth outcomesNeonatal outcomesMaternal outcomes

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.

Impact of Depression :Neonatal Outcomes - Behavioural

More than one study showed that depression during pregnancy was correlated with greater 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


Impact of Depression on:Neonatal Outcomes- Behavioural

Increased risk for irritabilityDecreased activity and attentivenessFewer 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.

Impact of Depression During Pregnancy on the Mother

Vegetative symptomsSelf-harmSuicidePsychosisDepression 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. Obstet Gynecol 2000; 95: 487-490.

Antidepressant Treatment During Pregnancy

Treatment with Antidepressants

Majority of women with depression do not obtain treatment during pregnancy


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)


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.



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)



Stopping antidepressants during pregnancy, puts women at a higher risk for recurrence of depression.



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 discontinued medication relapsed significantly 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

Impact of Antidepressants During Pregnancy

Impact of Antidepressant Use During Pregnancy

Pregnancy lossGrowth reduction (reduced head growth, low

birth weight, small for gestational age)Preterm birthMalformationsNeonatal adaptionSlower neonatal and infant motor development Persistent pulmonary hypertensionInfant and child behavioural effectsMother’s health


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.

Birth Outcomes

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

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.

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. .

Malformations

Structural Malformations

• No association between SNRI use Conflicting data for TCA useConflicting data for SSRI use (specifically paroxetine)

Cardiac MalformationsNo increase in rate with SSRI use (4 studies)Increase risk in first trimester exposure to paroxetine

(three studies). Not found in three other studiesCombination 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

Low Birth Weight

Increased risk with SSRI or TCA use


Small for Gestational Age

Small increased risk with SSRI use compared with depressed mothers who did not take SSRIs


Preterm Delivery

Inconclusive relation

Some studies found an increased risk, others did not

More exposure, more likely to decrease gestational age


Neonatal Outcomes

BehaviouralPersistent Pulmonary HypertensionLong term growth, IQ, Behavioural

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


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


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


TREATING DEPRESSED PREGNANT WOMEN

Approach and Strategies

General Approach to Treating Depression During Pregnancy

Obtain thorough historyMeet with patient to review risk and benefits

at trimesters of pregnancyInter-professional collaboration with

obstetrician, pediatrician, and psychiatristIdentify triggers: have a plan if dose change

neededEncourage healthy lifestyleKnow limitations of studies“Big Picture” Approach


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


Strategies for Using Antidepressants in Pregnancy

Monotherapy, if possibleAvoid first trimester exposureAvoid first trimester antidepressant and

benzodiazepine combinationsContinue using antidepressants if depression

is severeTaper dose, do not stop suddenlyTreat to remissionUse lowest effective dose


Non-Pharmacological Measures

Psychotherapy alone or in combination with antidepressants

Individual/group therapiesBright light therapyECT (reserved for severe depression)No reports of impact on fetal, neonatal, or

birth outcomes


Topics to be Discussed at Each Trimester

First Trimester Exposure

Known and unknown risks for: Specific malformations Pregnancy loss or miscarriage


Second Trimester Exposure

Effects on: Fetal growth Birth weight Size for gestational age


Third Trimester Exposure

Effects on: Birth weight Size for gestational age

Risks for: Persistent pulmonary hypertension Neonatal adaptation syndrome


For The Clinician

Check out my website: depressionduringpregnancy.weebly.com

http://depressionduringpregnancy.weebly.com/

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

Summary

More is known about the effects of antidepressants on birth, neonatal, and maternal outcomes than depression itself

Keep in mind: many limitations in studies For women with mild-moderate depression

without a history of recurrent or severe depression, psychotherapy may be enough

If the patient’s history points to a need for an antidepressant-symptom severity, recurrence- consider treatment


Clinical Example

In Practice

A 25 year old woman comes into your family health team; 6 weeks pregnant.

History of recurrent major depression; Medications for the past 5 years:

Fluoxetine 40mg/day, Clonazepam 0.25 mg daily as needed

Had 1 suicide attempt; at 16 years oldHas been under the care of a psychiatrist

since 13 years old. Has taken sertraline, citalopram, venlafaxine, lithium, olanzapine in the past.

Has psychosocial support from a therapistAdapted from Chaudron LH. Complex Challenges in Treating Depression During Pregnancy. Am J Psychiatry 2013; 170: 12-20

In Practice

Mother has history of eating disorder, father and brother suffer from alcoholism

Miscarried 2 years ago at 7 weeks

Advice of the obstetrician: discontinue medication. Patient is worried that if she stops, she will relapse. She decreased her fluoxetine to 20mg 6 weeks ago and stopped clonazepam

Patient is worried about miscarriage, depressive relapse.

She is currently experiencing general anxiety and loss of appetite with some nausea.

Adapted from Chaudron LH. Complex Challenges in Treating Depression During Pregnancy. Am J Psychiatry 2013; 170: 12-20

What do you think?

Avoid use of clonazepam: Combination of SSRI and benzodiazepine may increase congenital heart defects

Decreasing the dose of fluoxetine to 20mg may or may not be enough for our patient

Monitor for anxiety and depression; If acute anxiety, clonazepam as needed? If persistent anxiety or depressive symptoms that are

not adequately met, may have to increase fluoxetine

QUESTIONS?

Thank you

References


De las Cuevas, Carlos and Sanz2, Emilio J. Safety of Selective Serotonin Reuptake Inhibitors in Pregnancy. Current Drug Safety, 2006, 1, 17-24 17

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

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.

Kurki et al. Depression and anxiety in early pregnancy and risk for pre-eclampsia. Obstet Gynecol 2000; 95: 487-490.

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

depression during pregnancy treatment with antidepressants

Documents

symptomatology of depression

effect of depression

complex challenges

j psychiatry

pregnancychaudron lh

infantschaudron lh

postpartum period interactions

adrenal hpa axis evidence