Depression in Pregnancy Case File

Depression in Pregnancy Case File

Eugene C. Toy, MD, Edward Yeomans, MD, Linda Fonseca, MD, Joseph M. Ernest, MD

Case 29

A 43-year-old G1 is currently at 7 3/7 weeks’ gestation, conceived by IVF (donor eggs) with a resultant dichorionic/diamniotic twin gestation. She presents for prenatal care. She denies a history of medical problems although endorses a history of three operative laparoscopic procedures due to a long history of chronic pelvic pain secondary to endometriosis. She got married earlier this year and desired to conceive. She failed to conceive due to infertility and ultimately required IVF. She admits to a history of depression since the age of 20. She has sought counseling and has been on antidepressants intermittently throughout the years. Most recently she was on sertraline; however, she stopped taking it prior to pregnancy because she thought this was contributing to her infertility issues. She is very excited about her pregnancy and thinks that she is doing “okay” off medications. She is a dentist and reports being happily married. There is no history of suicide attempts, substance abuse, or domestic violence.

➤ How would you screen this patient for depression?

➤ What are some neonatal/maternal risks associated with untreated depression during pregnancy?

ANSWERS TO CASE 29:

Depression in Pregnancy

Summary: A 43-year-old G1 at 73/7 weeks with twin gestation conceived by IVF and history of depression presents for prenatal care.

➤ Screening patient for depression: Screening questionnaires, such as the Edinburgh postnatal depression scale (EPDS) or Patient Health Questionnaire (PHQ) and clarification of the patient’s responses will help to determine whether she requires further assessment and/or treatment.

➤ Reasons for some neonatal/maternal risks associated with untreated depression during pregnancy: Neonatal irritability has been associated with untreated maternal depression. There is an increased risk of maternal stress/anxiety, poor weight gain, poor prenatal care, substance abuse, and postpartum depression/psychosis when depression goes untreated during pregnancy.

ANALYSIS

Objectives

1. Understand how to screen pregnant patients for depression.
2. Review pharmacologic options and their effect on pregnancy.
3. Understand which patients are candidates for treatment during pregnancy.

Considerations

This is a 43-year-old woman who presents with symptoms of depression. It is not uncommon that a patient provides a history of depression at her first prenatal care visit. Reproductive age women are at risk of developing a depressive disorder and the perinatal period (defined as pregnancy and up to 1 y postpartum) represents a time of increased vulnerability. The incidence of depressive disorders during pregnancy is in the order of 10% to 16% of women.1 Major depression as defined by the diagnostic and statistical manual-IV occurs in 3% to 5%, while the remainders of cases are minor depression2 (Level III). This may actually be an underestimation since the diagnosis is not always an easy one to make because symptoms of depression may overlap with those of pregnancy.

The strongest risk factor for perinatal depression is a history of depression. Additional risk factors include a history of postpartum depression (onset of symptoms within 4 wk), low-income status, ethnic minority, domestic violence, financial hardship, poor social support, high-risk pregnancy, and family history of depression. Despite increasing knowledge of risk factors, it is difficult to identify which women will actually develop perinatal depression. That said, screening for depression during pregnancy is an important part of prenatal care and all women should be screened.

Depression screening is recommended “at least once during each trimester” per the American College of Obstetricians and Gynecologists.3 Postpartum depression screening is also recommended and this most commonly occurs in conjunction with the 6 week visit. However, it should be noted that the most vulnerable period after delivery is 10 to 19 days followed by 3 months, with most cases occurring by 5 months. A widely quoted rule of thumb for postpartum depression screening is “2 weeks, 6 weeks, 6 months”2 (Level III). Although it is challenging to coordinate multiple postpartum screening visits, it should be considered for high-risk women. It is also important to distinguish postpartum depression from postpartum blues. The latter occurs in 80% of women. Symptoms are mild and self-limiting, typically resolving by 2 to 3 weeks postpartum.

Self-report screening is routinely used in clinical practice during the perinatal period. It is important to note that these questionnaires are not diagnostic but rather are used to determine which patient requires further assessment and treatment. The Edinburgh postnatal depression scale is a 10-item questionnaire and perhaps the most widely used tool for depression screening during the perinatal period. A score of 15 or more in the antenatal period and 13 or more in the postnatal period is considered a validated cutoff score for probable major depression.4 (Level III). The detection rates are better for severe depression with specificity of approximately 78% to 96%. The nine-item patient health questionnaire is also a validated screening instrument and has been studied in the obstetric-gynecologic setting5 (Level II-2). This questionnaire takes 3 minutes to complete and permits planning and monitoring of treatment.

It is not unreasonable for this patient to be observed off of medication if she is currently euthymic and does not have other risk factors for relapse. If she becomes symptomatic, the patient can be restarted on pharmacotherapy and referred for adjunct psychotherapy (individual, couples, or group) as well. Based on a recent cohort study, she can be informed that her risk of relapse may be as high as 68% by having discontinued medication as compared to a lower risk of 25% if she remains on medication during pregnancy6 (Level II-2). The risks of untreated depression as well as the risk of prenatal exposure to antidepressants should be reviewed with the patient.

Untreated depression during pregnancy has been associated with stress, poor prenatal care, substance abuse, and postpartum depression/psychosis, all of which can impact fetal/neonatal outcome. Based on the available evidence, infants born to mothers with a depressive disorder have increased risk of irritability making them more difficult to console. They are also less attentive and have fewer facial expressions7 (Level III). Increased cortisol levels, as seen in those with depression, may precipitate preterm birth (PTB). At present, the data looking at the association between untreated depression during pregnancy and adverse pregnancy outcomes such as miscarriages, PTB, or small-for-gestational-age infants (SGA) are inconsistent. Some studies report an association while others do not, thus a definitive conclusion is difficult to make based on the available data8,9 (Level III).

Healthy lifestyles should be supported and treatment of any addictions (ie, tobacco, alcohol) should be offered in order to optimize maternal/fetal outcome. It is also important to review the patient’s medication list given that side effects from antihypertensive medications (ie, beta blockers), diuretics, corticosteroids, and sedatives can mimic depression. This patient should be provided with education material such as perinatal/postpartum depression booklets and resource contact numbers/and or web sites.

APPROACH TO

Depression in Pregnancy

CLINICAL APPROACH

A large majority of women who fulfill criteria for depressive disorder may experience symptoms during pregnancy. Those who are considered at high risk for relapse during pregnancy and therefore would benefit from continued or initiation of treatment during pregnancy include those with a history of severe or recurrent major depression, psychosis, history of suicide, coexisting panic or bipolar disorders, and history of relapse after discontinuation of antidepressants. The decision on whether to treat or discontinue pharmacotherapy during pregnancy can be made based on severity of symptoms, risk factors, and individual preference. Collaboration between the obstetrician and psychiatrist is important when considering this decision. It goes without saying that a patient with suicidal or psychotic features should be seen immediately by a psychiatrist who can optimize treatment. Those with coexisting bipolar disorders should also be managed by a psychiatrist as initiation of antidepressant monotherapy may trigger mania and psychosis8,9 (Level III).

Those who are on antidepressant medication during pregnancy and are asymptomatic (preferably > 6 mo) can be offered a trial off medication with a slow taper provided they do not have any of the above risk factors for relapse and are willing to be off medication. If the patient is motivated to have a trial off medication, it is important to monitor her closely for signs/symptoms of relapse. Again it is important to review with the patient that her risk of relapse is higher after discontinuing medication during pregnancy and that this risk must be weighed against the potential risks of antidepressant medication use during pregnancy. It is always reasonable to refer a patient for psychotherapy especially when a trial off medication is considered. If a patient chooses to continue on medication during pregnancy or is not a candidate for discontinuing medication, then she should remain on the same medication at the lowest effective dose.

Those who have symptoms of major depression but are not receiving any treatment can be offered initiation of antidepressant therapy and adjunct psychotherapy. Sometimes a patient may choose psychotherapy before starting pharmacotherapy. This is a reasonable option as long as the patient is not debilitated and is without risk factors such as a prior failed trial of psychotherapy alone or recurrent, severe relapses. If a patient requires pharmacotherapy, the drug safety profile should be factored into the particular antidepressant that is selected. It is also reasonable to select an antidepressant that the patient has responded well to in the past. Selective serotonin reuptake inhibitors (SSRIs) remain the first-line choice for treatment. Counseling regarding the risks and benefits of antidepressant use during pregnancy should be undertaken and weighed against the risks of untreated depression. Electroconvulsive therapy is also a safe and effective alternative to treatment in those with severe depression unresponsive to pharmacotherapy.

There are two recent publications by representatives from the American Psychiatry Association and the American College of Obstetricians and Gynecologists who convened a working group to critically evaluate the existing literature on the risks of depression and antidepressants during pregnancy8,9 (Level III). Some studies have reported an increased risk of miscarriage in the first trimester in those exposed to various antidepressants; however, it is difficult to establish this association when confounding variables such as substance abuse and maternal age were not well controlled in these studies.10 Conflicting evidence exists with regard to the use of antidepressants and SGA infants. Selective serotonin reuptake inhibitors (SSRIs) have been associated with an increased risk of SGA infants, albeit very small, compared to unexposed group after controlling for confounding variables11 (Level II-2). Although some studies suggest that the use of SSRIs during pregnancy may be associated with an increased risk of PTB12 (Level II-2), data are not consistent across all studies.

With regard to structural malformations, the current data on SSRI exposure during pregnancy do not provide consistent information to support major or specific teratogenic risks8,9 (Level III). Although linked databases have found that pregnancies exposed to paroxetine during the first trimester have an increased risk of cardiac malformations13 (Level II-2), other large cohort studies have not supported this association14 (Level II-2). A higher incidence of congenital heart defects has been seen with the use of SSRI in combination with benzodiazepine as compared to SSRI alone15 (Level II-2) and therefore monotherapy in the treatment of depression is recommended. The majority of tricyclic antidepressants (TCAs) have not been associated with structural defects. Other antidepressants are not as well studied; however, no specific malformation has been associated with the use of bupropion or venlafaxine.

Infants born to mothers who used TCAs during pregnancy have an increased risk of neonatal behavioral symptoms such as jitteriness, irritability, and convulsions16 (Level II-2). Approximately one-third of women using SSRIs in late pregnancy had infants with transient “poor neonatal adaptation” with symptoms in the immediate newborn period consisting of hypoglycemia, irritability, temperature instability, seizures, tachypnea, and/or weak absent cry. The absolute risk of persistent pulmonary hypertension (PPH) among newborns has also been shown to be increased in mothers who used SSRIs late in pregnancy (3-6 per 1000 infants compared to 0.5-2 per 1000 infants baseline)8,9 (Level III). The data on the use of antidepressants (sertraline, fluoxetine, paroxetine, fluvoxamine, citalopram) during lactation show that exposure through breast milk is considerably lower than transplacental exposure during pregnancy. Sertraline is considered the safest for lactation and therefore the first choice when considering which antidepressant to start during pregnancy and in the postpartum period2 (Level III). TCAs have been well studied and similarly considered safe for use during lactation although one report of respiratory depression was reported with the use of doxepin.1 Other antidepressants are less well studied and therefore patients need to be counseled appropriately.

In summary, depression in reproductive age women is common. Awareness of this illness is important given that pregnancy and the postpartum period are times when a woman is at high risk for developing depression or having a relapse. Collaboration of care between the obstetrician and the mental health provider will ensure optimal maternal health care. The decision to initiate or discontinue treatment needs to be individualized based on the patient’s symptoms and psychiatric history. The risks and benefits of untreated depression need to be weighed against the potential fetal/neonatal risks of antidepressant use during pregnancy.

Postpartum Depression

Postpartum depression, which usually occurs within the first 3 to 4 months after delivery, affects 10% to 15% of women. The clinical symptoms and diagnostic criteria are identical to depression that can occur any other time in a woman’s life. Women in the postpartum period are most vulnerable to develop psychiatric illness. Women who have suffered one major episode of postpartum depression have about 25% recurrence risk. Those at highest risk are those with a personal history of depression, previous episode of postpartum depression, or depression during pregnancy. In addition to a history of depression, recent stressful life events, lack of social support, unintended pregnancy, and uninsured status are also risk factors.

Usually, postpartum depression develops slowly over the first 3 to 4 months after delivery although the disorder presents more abruptly. Postpartum blues are more mild and do not meet the same diagnostic criteria as postpartum depression. Screening for, diagnosing, and treating depression are critical to proper intervention. Women with current depression or a history of major depression are at particular risk, and should be monitored carefully.

Unfortunately, too many women tragically fall “through the cracks” such that they themselves or their children become victims to the depression. Pregnancy and the postpartum period represent an incredibly important time to assess for mood disturbance.

There are multiple depression screening tools available for use. These tools usually can be completed in less than 10 minutes. Most have a specificity ranging from 77% to 100%. Thus, it can be argued that sensitivity should be the determining factor to maximize the number of depressed patients identified. Many of these screening tools have been validated with specific ethnic populations. Examples of highly sensitive screening tools include the Edinburgh postnatal depression scale.

Comprehension Questions

29.1 A 28-year-old G1P0 at 18 weeks’ gestation reports a history of sertraline use for the treatment of depression. What is the best management for this patient?

A. Recommend to discontinue medication.

B. Recommend fetal echocardiogram.

C. Recommend anatomy scan at 18 to 20 weeks gestation and continue treatment.

D. Recommend termination of the pregnancy.

29.2 A 30-year-old G2P1 woman at 32 weeks’ gestation is noted to have a history of postpartum depression. She required SSRI antidepressant therapy after the last delivery. She asks about the possibility of postpartum depression after this current pregnancy. Which of the following statements is most accurate?

A. Each pregnancy is independent and the prior postpartum depression should have no impact on this pregnancy.

B. The criteria for postpartum depression is identical to that of nonpregnant patients.

C. The Edinburgh depression scale is more valid for nonpregnant than pregnant individuals.

D. Postpartum depression affects approximately 1% to 3% of postpartum women.

ANSWERS

29.1 C. This patient should be encouraged to continue on treatment as the risks of untreated depression are greater than the risks of treatment during pregnancy. Data on SSRI exposure during pregnancy do not provide consistent information to support major or specific teratogenic risks and therefore routine anatomy scan is a reasonable start for the evaluation of this patient. If there is a cardiac abnormality on ultrasound then she can be referred for fetal echocardiogram.

29.2 B. The criteria for postpartum depression are identical to that of depression outside of pregnancy. A history of depression is a risk factor for postpartum depression. The Edinburgh depression scale was developed to identify postpartum depression. Postpartum depression affects approximately 10 to 15 of women after delivery.

Clinical Pearls

See US Preventive Services Task Force Study Quality levels of evidence in Case 1

➤ Perinatal depression is common and is associated with increased risk of maternal and neonatal adverse outcomes (Level III).

➤ Pharmacotherapy should be continued during pregnancy in those who are at high risk of relapse (Level III).

➤ SSRIs are the drug class of choice when treating depression during pregnancy or postpartum (Level III).

➤ SSRIs are associated with a small increased risk of SGA infants, poor neonatal adaptation,and persistent pulmonary hypertension in the newborn (Level II-2).

➤ Current data on SSRI exposure (in aggregate) during pregnancy do not provide consistent information to support major or specific teratogenic risks (Level II-2).

CONTROVERSIES

• Association of antidepressants and increased risk of miscarriages and PTB.

• First-trimester use of paroxetine and increased risk of cardiac malformations.

REFERENCES

1. Use of psychiatric medications during pregnancy and lactation. ACOG Practice Bulletin No. 102. American College of Obstetricians and Gynecologists. Obstet Gynecol. 2008;111(4):1001-1020. 

2. Dossett EC. Perinatal depression. Obstet Gynecol Clin N Am. 2008;35:419-434 (Level III). 

3. American College of Obstetricians and Gynecologists. ACOG Committee Opinion No. 343. Obstet Gynecol. 2006;108:469-477. 

4. Matthey S, Henshaw C, Elliot S, Barnett B. Variability in use of cut-off scores and formats on the Edinburgh postnatal depression scale—implications for clinical and research practice. Arch Womens Ment Health. 2006;9:309-315 (Level III). 

5. Spitzer RL, Williams JBW, Kroenke K, Hornyak R, McMurray J. Validity and utility of the PRIME-MD patient health questionnaire in assessment of 3000 obstetricgynecologic patients: the PRIME-MD patient health questionnaire obstetricgynecologic study. Am J Obstet. 2000;183(3):759-769 (Level II-2). 

6. Cohen LS, Altshuler LL, Harlow BL, et al. Relapse of major depression during pregnancy in women who maintain or discontinue antidepressant treatment [published erratum appears in JAMA 2006;296:170]. JAMA. 2006;295:499-507. A prospective cohort of 201 pregnant women with a history of depression who were recently or currently on antidepressant medication. Of those who remained on treatment during pregnancy, 26% relapsed compared to 68% who discontinued treatment (Level II-2). 

7. Field T, Diego M, Hernandez-Reif M. Prenatal depression effects of the fetus and newborn: a review. Infant Behav Dev. 2006;29:445-455 (Level III). 

8. Yonkers KA, Wisner KL, Steward DE, et al. The management of depression during pregnancy: a report from the American Psychiatric Association and the American College of Obstetricians and Gynecologists. Obstet Gynecol. 2009;114(3):703-713. Representatives from the American Psychiatry Association and the American College of Obstetricians and Gynecologists convened a working group to critically evaluate the existing literature on the risks of depression and antidepressants during pregnancy (Level III). 

9. Yonkers KA, Wisner KL, Steward DE, et al. The management of depression during pregnancy: a report from the American Psychiatric Association and the American College of Obstetricians and Gynecologists. Gen Hosp Psychiatry. 2009;31(5):403-413. See reference number 8 (Level III). 

10. Hemels M, Einarson A, Koren G, Lanctot K, Einarson T. Antidepressant use during pregnancy and the rates of spontaneous abortions: a meta-analysis. Ann Pharmacother. 2005;39:803-809. 

11. Oberlander T, Warburton W, Misri S, Aghajanian J, Hertzman C. Neonatal outcomes after prenatal exposure to selective serotonin reuptake inhibitor antidepressants and maternal depression using population-based linked health data. Arch Gen Psychitary. 2006;63:898-906 (Level II-2). 

12. Chambers CD, Johnson KA, Dick LM, Felix RJ. Birth outcomes in pregnant women taking fluoxetine. N Eng J Med. 1996;335:1010-1015 (Level II-2). 

13. Kallen BA, Otterbald Olaussan P. Maternal use of selective serotonin reuptake inhibitors in early pregnancy and infant congenital malformations. Birth Defects Res A Clin Mol Teratol. 2007;79:301-308 (Level II-2). 

14. Louik C, Lin A, Werler M, Hernandez-Diaz S, Mitchell A. First trimester use of selective serotonin-reuptake inhibitors and the risk of birth defects. N Eng J Med. 2007;356:2675-2683 (Level II-2). 

15. Oberlander TF. Major congenital malformations following prenatal exposure to serotonin reuptake inhibitors and benzodiazepines using population-based health data. Birth Defects Res B Dev Reprod Toxicol. 2008;83:68-76 (Level II-2). 

16. Kallen B. Neonate characteristics after maternal use of antidepressants in late pregnancy. Arch Pediatr Adolesc Med. 2004;158:312-316 (Level II-2).

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