PERINATAL DEPRESSION

Identifying perinatal depression—sooner is better

By Megan V. Smith, MPH, Wendy Lee Brunetto, MPH, and Kimberly A. Yonkers, MD

Depression does occur in pregnant women and not just those with preexisting mood symptoms. Knowing how to detect the disorder and when to refer is important because you may be the only physician these patients see during the perinatal period.

Unfortunately there are still some clinicians and patients who believe that pregnant women don't suffer from severe depression. But roughly one in four women will have depressive symptoms during pregnancy—and perhaps worst of all, a mother with depression doesn't suffer alone. Her decreased ability to function and her poorer quality of life can harm her offspring as well.

In this first installment of a two-part article on depression in women, our goal is to raise awareness among ob/gyns of the prevalence and symptoms of major and minor depression before, during, and after pregnancy, and to underscore the importance of screening for it during pregnancy and providing prompt treatment. As you become familiar with screening, you may wish to refer patients to a psychiatrist or coordinate your efforts. But first let's look at how depression during and after pregnancy affects mother and child.

Far-reaching effects of depressive illness

A depressed pregnant or postpartum woman is riddled by anxiety, guilt, and agonizingly low mood. Over and above the usual symptoms of depression, she may obsess about harm that could come to her child or have intrusive thoughts about hurting herself and her unborn child.^1-3 She can't eat or sleep and if she's postpartum, she may not be able to "get her act together" to properly care for her baby. Her depressive illness robs a woman of both the experience and the joy that should accompany new motherhood. Relationships with her husband or other important adult family members, and other children or her newborn all suffer. So huge is the impact of a peripartum depressive episode that one third of these women will change their plans and decide not to bear another child.⁴

Diagnosing major depression. The hallmarks of major depression are a sustained depressed mood, loss of interest or pleasure in activities and relationships, or both. The diagnostic criteria for major depressive disorder (MDD) (Table 1) stipulate that a person must suffer from at least five of nine possible symptoms, at least one of which must be depressed mood or diminished interest and pleasure.⁵ Behavioral symptoms on the list like appetite, energy, and sleep show how the illness can affect the body.

TABLE 1
Symptoms of perinatal depressive disorders

Depressed, low or blue mood most of the day, nearly every day*

Markedly diminished interest or pleasure in most, if not all, activities*

Decrease or increase in appetite nearly every day

Insomnia or hypersomnia nearly every day

Psychomotor agitation or retardation nearly every day

Fatigue or loss of energy nearly every day

Diminished ability to think or concentrate, or difficulty making decisions nearly every day

Feelings of worthlessness or excessive or inappropriate guilt nearly every day

Recurrent thoughts of death, suicidal ideation, or a suicide attempt or specific plan

Misinterpretation of baby's cues (postpartum)

Complaints of lack of social support

* One of the starred items is requisite for the diagnosis

Diagnosing minor depression. A diagnosis of minor depressive disorder (Min D) requires three or four symptoms, and while typically less severe, is still associated with considerable impairment.⁶

To be diagnosed as either MDD or Min D, a patient must have had symptoms for at least 2 weeks; usually both illnesses last from 1 to several months.^6-8 A woman suffering from either disorder will have many symptoms nearly every day, nearly all day long, according to the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV).

Both the severity and duration of symptoms take their toll in biological and interpersonal terms during and after pregnancy. For example, a poor appetite week after week and month after month can lead to poor maternal weight gain or weight loss.

Depressive symptoms affect one in four gravidas

While about 25% of women will have depressive symptoms during pregnancy, the incidence is even higher among adolescents and poor minority women.^9-14 Of that latter group, between 2% and 11% of women will experience the full syndrome of MDD at some point during pregnancy.^14-17 Consistent evidence shows that MDD, Min D, or depressive symptoms are at least as common in pregnant women as in postpartum^{9,10,12,14,18-22} or nonpregnant women.^15,23,24

The length and onset of depressive disorders during pregnancy vary, with many episodes begin-ning and ending within one to three trimesters. One study shows that more than 30% of women will be depressed for at least one trimester but other data show that a large percentage of women (25%) have depression in one trimester but not another. (Yonkers, unpublished manuscript). In one of a handful of studies to assess depressive disorders over the length of a pregnancy, 15% of women experienced MDD but one third of the 15% did not develop the illness until after the first trimester.²²

As we've said, limited data suggest that the rate of unipolar mood disorders is similar during and after pregnancy. However, there's much more information on the rates of depressive symptoms and disorders in postpartum women compared to pregnant women. Roughly 10% to 20% of women will suffer from an episode of depression within the first 6 months of childbirth.^{11,15,22,25-33}

Despite inconsistent findings, some work suggests that after childbirth women are at 12% to 15% higher risk for serious depressive illness than are nonchildbearing women.³⁴ A recent large study of 6,000 women estimated the 2-month prevalence for postpartum-onset of MDD at 15%.²⁵ And while another study also estimates prevalence of MDD at 15% immediately postpartum, the illness had struck nearly one half of those women prior to delivery.³⁵ Acute postpartum onset of psychosis occurs less frequently (in roughly 1 in 500 to 1,000 births); it strikes within the first few days to 2 to 3 weeks postpartum.

Clinical course of postpartum-onset depression

The initial episode of postpartum-onset depression begins within the first 4 weeks after delivery. A mother with a severe episode may continue to suffer from depression for up to 2 years. DSM-IV now contains a course-specific modifier, "postpartum onset," that can be applied to the current or most recent Major Depressive, Manic, or Mixed Episode in MDD, Bipolar Disorders, or to Brief Psychotic Disorder. For this designation to apply, the onset must be within 4 weeks of parturition.⁵

An earlier study had suggested that most women with postpartum depression recover within 6 months.²² But recent research suggests otherwise, namely that 20% of women will have chronic depression lasting more than 2 years.³⁶ Longer-term follow-up indicates substantial recurrence: Over the next 4 years, 50% of women with postpartum depression either felt the need to continue or again sought treatment.^22,37 Women whose first bout with depression occurs after childbirth are more likely to have a subsequent postpartum episode, whereas women with an index episode prior to delivery have more recurrences.^38-40 While limited, these data on course suggest a substantial risk for chronic depression and lifetime recurrence whether the postpartum episode was the first depressive event or a recurrence.

Overlap between pregnancy and depression

Clinicians may overlook some symptoms of depressive syndromes because they're also common during pregnancy. Frequent changes in sleep, appetite, and energy (neurovegetative symptoms), for example, are not unusual, during the first and third trimesters.⁴¹ Because they're so common in pregnancy, some practitioners may fail to ask pregnant patients about neurovegetative symptoms.^8,42

While the overlap between symptoms of normal pregnancy and of depression does pose a dilemma, labeling a pregnant women's alterations in sleep, energy, and appetite as "normal" is problematic. Pregnant patients with depression are more likely than those not depressed to complain of sleep deprivation and fatigue.⁴³ Depressed patients may shy away from disclosing their depression to a health-care provider, but may be willing to own up to behavioral changes. And depressed patients often fail to recognize that they're mentally ill and often attribute it to having a cold, being tired, and to overwork. It's therefore important to take into account cognitive as well as behavioral and somatic symptoms.

Risk factors for perinatal depression

The litany of risk factors associated with depression during pregnancy and the puerperium include a history of depressive disorders, diminished partner support or marital difficulties,^{12,22,30,44-48} poor social adjustment,¹¹ adverse life events,^{30,32,44,29-51} unplanned pregnancy or uncertainty about having the child,^22,52 and maternal or paternal unemployment (Table 2).^2,52 Additional risk factors specific to postpartum depression are depressive symptoms during pregnancy^{15,30,44,53,54} obstetric risk factors like a difficult pregnancy, abortion, or miscarriage,²² and adolescence.^12,26,55,56 Although some researchers find higher rates of depressive disorders in selected ethnic minorities (including Hispanic-Americans and African-Americans),⁵⁷ there's greater consensus that it's the interaction between income and ethnic status that raises the risk for depression.^58-61 Thus, it comes as no surprise that low-income inner-city women have double the rates of depressive disorders of women who come from more socioeconomically advantaged backgrounds (Table 2).⁴⁸

TABLE 2
Risk factors for depression during pregnancy

History of depressive disorders

An absent, abusive, or nonsupportive spouse, or marital difficulties

Adverse life events

Unplanned pregnancy or uncertainty about having a child

Maternal or paternal unemployment

Obstetric factors: depression during a past pregnancy, abortion, miscarriage

Personality organization: difficulty with change, obsessive compulsive disorder traits, need for control

Poverty

Risk factors for postpartum depression

All of the above plus:

Depressive symptoms during pregnancy

Delivery complications

Loss of baby

Age (adolescents are at increased risk)

How maternal depression affects the fetus

A growing body of evidence suggests that psychosocial factors, including stress and depression, may increase the likelihood of adverse perinatal outcomes. A series of studies have addressed the importance of depression as a risk factor for preterm delivery (PTD), low birthweight (LBW), and intrauterine growth restriction (IUGR). In most of these studies, psychosocial distress was predictive of adverse perinatal outcomes.^62-68 But not always.^69-72 For example, one study linked depression dur-ing pregnancy with delivering a preterm baby and having an LBW infant.⁶⁷ Another found that women with the most depressive symptoms during pregnancy were twice the risk for PTD.⁶⁴

Furthermore, postnatal depression can hinder infant behavior, cognitive development, and emotional well being.^73-76 And these effects are long-lasting, as shown by findings of impaired cognitive development in 4-year-olds whose mothers had suffered depression when the children were infants.^77,78 Supporting the need for intervention, a recent prospective study found that chronic maternal depression seems to increase the likelihood of negative behavior and affect in the child.⁷⁴ Furthermore, depression's postnatal impact is most profound for socioeconomically disadvantaged children.^79-83 Finally, the child of a depressed adolescent mother is at particularly high risk.^56,84

Screening for depression during pregnancy

It's critical to intervene early on if you hope to minimize the effects of maternal depression. This and the fact that mood disorders are more common during the third trimester than in the 8 months thereafter support the idea that depression screening and intervention needs to occur when a woman is pregnant.⁹ In fact, a woman's frequent contact with the health-care system during pregnancy makes it an ideal time for screening.

Depression screening scales are a cost-effective way for primary-care physicians to detect depression. While community and clinic needs will dictate your choice of screening tool, keep in mind that recognizing depression in and of itself isn't enough to improve the treatment of depressed perinatal women. That will only happen if clinicians are equipped with the skills and resources to deliver adequate intervention. When implementing a screening protocol, consider whether behavioral health-care professionals are accessible on site or by phone and how a patient who screens positive will be assessed and referred.

There are several strategies for identifying mood disorders. Screening instruments can measure either general distress and dysphoria or depression specifically. Screening scales include the Edinburgh Postnatal Depression Scale (EPDS), Inventory of Depressive Symptomatology (IDS), or Primary Care Evaluation of Mental Disorders (PRIME-MD) depression module (Table 3).^85,86 The EPDS, while less comprehensive than the IDS, is specifically designed for pregnant and postpartum women. Its 10 items measure the severity of depressive symptoms. The IDS measures the severity of cognitive features of depression/anxiety and reverse neurovegetative symptoms of depression. Even though the IDS is short (28 to 30 items), it is comprehensive. Finally, the PRIME-MD, which records diagnoses of MDD and Min D, has been used in obstetric/gynecological settings, and takes from 5 to 20 minutes to complete.

TABLE 3
Measures of distress and dysphoria

Edinburgh Postnatal Depression Scale (EPDS)

10-item self-report questionnaire

Detects symptoms of postpartum depression and depression during pregnancy

10 minutes to complete

Cox JL, Holden JM, Sagorsky R. Detection of postnatal depression: development of the 10-item Edinburgh Postnatal Depression Scale. Br J Psychiatry. 1987;150:782-786. Copyright permission must be obtained from the Royal College of Psychiatrists, Mr. David Jago, British Journal of Psychiatry, 17 Belgrave Square, London SW1X8PG, United Kingdom.

Depression-specific measures

PRIME-MD depression module

14-item self-report questionnaire (accompanying clinician evaluation guide)

Provides diagnosis of major and minor depressive disorders and measures of severity

5 to 20 minutes to complete

Copies and permission to use can be obtained by e-mailing: Robert L. Spitzer, MD, Chief, Biometrics Research and Professor of Psychiatry, Columbia University; e-mail: RLS8@Columbia.edu

Inventory of Depressive Symptomatology (IDS)

28 to 30 item self-report form (IDS-SR) or clinician-administered (IDS-C) form

Provides measure of illness severity

15 to 30 minutes to complete

Copies and permission to use can be obtained by writing: John Rush, MD, University of Texas SW Medical Center, 5323 Harry Hines Blvd., Dallas TX 75235-9101.

An advantage of the PRIME-MD and the IDS is that they provide a syndromal diagnosis of Min D or MDD, in addition to measuring the severity of depressive symptoms. However, a shortcoming of the other screening instruments such as the EPDS is that they're not able to diagnose depression specifically but are elevated by general emotional distress, concurrent psychiatric illness, or general medical conditions.⁸⁷ The EPDS is an integral part of the algorithm we use to diagnose and treat depression during pregnancy (Figure 1).

Effects of psychotropic drugs during pregnancy

Clinical guidelines are available for managing pregnant women with both unipolar and bipolar depression.^88-90 All psychotropic medications readily cross the placenta, making the decision to prescribe them during pregnancy complex. The Food and Drug Administration has assigned risk categories to all drugs based on the level of risk posed to the fetus if exposed to the drug in utero (Table 4). Keep in mind that the assigned risk category is subject to change because it's based on the latest data from both animal studies and well-controlled studies of pregnant women. Therefore, a drug is often re-classified to a different risk category as more data become available.

TABLE 4
FDA risk-in-pregnancy ratings for medications

Category A: Adequate, well-controlled studies in pregnant women have not shown an increased risk of fetal abnormalities.

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.

Category C: Animal studies have shown an adverse effect and there are no adequate and well-controlled studies in pregnant women.

OR

No animal studies have been conducted and there are no adequate and well-controlled studies in pregnant women.

Category D: Studies, adequate well-controlled or observational, in pregnant women have demonstrated a risk to the fetus. However, the benefits of therapy may outweigh the potential risk.

Category X: Studies, adequate well-controlled or observational, in animals or pregnant women have demonstrated positive evidence of fetal abnormalities. The use of the product is contraindicated in women who are or may become pregnant.

Source: US Food and Drug Administration. Current categories for drug use in pregnancy. Available at: http://www.fda.gov/fdac/features/2001/301_preg.html#categories . Accessed February 19, 2004.

There have been several prospective controlled studies of pregnant women taking tri-cyclic antidepressants (TCAs) and the selective serotonin reuptake inhibitor (SSRI) fluoxetine. Overall, they've shown no major teratogenic effects associated with these drugs and support their safety throughout pregnancy.^89,92,93 Although data on the SSRI sertraline during pregnancy are somewhat harder to come by, findings are equally benign. Prospective studies conducted on pregnant women have shown that exposure to sertraline was not associated with an increased risk for fetal malformations.^93-95 Additionally, studies examining the long-term developmental outcomes of children exposed to certain TCAs and SSRIs in utero have failed to demonstrate that exposure to these agents significantly affects global IQ, language development, or behavioral development.^96-99

Finally, there is some controversy regarding the effects that SSRIs and TCAs have on PTD and LBW. For example, Simon and colleagues found significantly lower gestational ages and birthweights among infants exposed to an SSRI in utero, but not among those exposed to a TCA.¹⁰⁰ Similar results were reported by others, who also found significant differences in gestational ages and birthweight among infants exposed to an SSRI in the first trimester.^93,101 On the other hand, Chambers and colleagues found that only exposure to the SSRI during the third trimester was related to PTD.⁹²

The jury is still out on the safety of benzodiazepines for treating depression during pregnancy, as they have been associated with cleft lip and palate. Their potential teratogenicity remains controversial and warrants further investigation.¹⁰² Therefore, benzodiazepines during pregnancy are discouraged because safer and equally effective therapies are available, such as the TCAs and SSRIs previously described. Table 5 lists the FDA's category of risk for several psychotropic drugs.

TABLE 5
FDA’s risk factor categories for use of psychotropic medications during pregnancy

Unfortunately, because selected mood-stabilizing agents like valproic acid and carbamazepine are known teratogens, they should never be used during pregnancy.¹⁰³ The literature on lithium does not exclude its use during pregnancy. Rather, lithium can be used during pregnancy with close monitoring of maternal blood levels.⁹⁰ On the other hand, data regarding the safety of lamotrigine are promising as it appears to be associated with a lower rate of fetal malformations. However, more studies need to be conducted on the use of lamotrigine during pregnancy.⁹⁰

Lastly, available data on exposure to the antipsychotic agent chlorpromazine suggest a statistically significant increased risk for nonspecific teratogenic effects.¹⁰⁴ Therefore, if an antipsychotic agent must be used during pregnancy, many clinicians feel that haloperidol is the drug of choice, given research that suggests it's not linked with an increased risk for fetal malformations.¹⁰⁴ Despite limited data on the newer antipsychotic agents risperidone, clozapine, and olanzapine during pregnancy, preliminary results show that olanzapine doesn't seem to pose a significant risk to the fetus or newborn infant.¹⁰⁵

Drug therapy during lactation

Any psychotropic drugs a nursing mother takes will be excreted in her breast milk.⁹¹ Therefore, factors in deciding whether or not to prescribe psychotropic drugs to nursing mothers include the benefits of breastfeeding to the infant, the severity of the mother's depressive symptoms if left untreated, and the potential risk to the infant should psychotropic drugs be ingested via breast milk. In general, the amount of psychotropic drugs excreted in a mother's breast milk is minimal and the risk to the infant is small.¹⁰⁶ For instance, several studies have examined the use of SSRIs in breastfeeding mothers.^107-115 Overall, results suggest that the level of SSRIs detected in breast milk is minimal. Moreover, infants' exposures to these drugs through breast milk don't seem to hinder their growth or development.^113-115

To date, data are limited on TCA use among nursing mothers. However, these studies indicate either undetectable or only trace levels of the drug in the infants' plasma and urine, and that none of the infants displayed any adverse effects.^116-119 Certain mood-stabilizing agents, such as lithium, however, are a different story. Breastfeeding mothers should not use them, because the milk levels are approximately 40% to 50% of the maternal serum concentration, and are potentially toxic to the nursing infant.⁹¹ General guidelines for the treatment of bipolar disorder are available from the American Psychiatric Association, but additional issues arise when applying these guidelines to peripartum women.¹²⁰ The American Academy of Pediatrics advises against taking lithium while breastfeeding. Likewise, the American Academy of Pediatrics recommends that breastfeeding mothers do not use antipsychotic agents, given the lack of available human data about their safety during lactation.¹²¹

Alternatives to drug therapy

Because all psychotropic medications readily cross the placenta and are excreted in breast milk, clinicians, in consultation with psychiatrists, face the hard choice of whether to use drugs to treat depression in pregnant and breastfeeding women. As such, some women will benefit from nonpharmacologic treatments, like interpersonal psychotherapy (IPT), cognitive behavioral therapy (CBT), and other forms of alternative therapy that have been proven effective.

To date, important work has emphasized the effectiveness of IPT in pregnant and postpartum women. A controlled study of 99 women with postpartum depression found that women receiving 12 weeks of IPT improved at double the rate of wait list controls.¹²² Other research has shown the effectiveness of cognitive behavioral therapy—as well as eight sessions of counseling by "health visitors"—among pregnant and postpartum women.¹²³ Given that for certain women, nonpharmacologic therapies can be safe and effective alternatives, clinicians should consider them a viable option.

Conclusions

We've tried to provide an overview of the latest tools obstetricians will need to identify, assess, and treat women presenting with depression. Early detection and treatment of women with depression is crucial, given the many perinatal women who suffer from this mental illness and considering the morbidity it causes in both mother and infant. For many pregnant women, the only physician they will see is an obstetrician/gynecologist. Thus, it is imperative that ob/gyns make efforts to address depression and become familiar with screening techniques and local mental health resources for perinatal women.

Dr. Yonkers serves as a consultant for and receives grant and research support from Eli Lilly, GlaxoSmithKline, and Berlex Laboratories. She receives grant and research support from Pherin Pharmaceuticals and serves as a consultant to Pfizer and Wyeth-Ayerst.

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Ms. Smith is a Research Associate, Department of Psychiatry, Ms. Brunetto is a Research Associate, Department of Epidemiology and Public Health, and Dr. Yonkers is Associate Professor, Department of Psychiatry, Yale University School of Medicine, New Haven, Conn.

Key points

• Depression can occur any time during pregnancy, becomes chronic (lasting 2 years or more) in 20% of women, and will recur in 50% within the next 4 years.

• All psychotropic medications readily cross the placenta and are excreted in breast milk. None are FDA-approved for use in pregnancy.

• Tricyclic antidepressants and selective serotonin reuptake inhibitors are far safer than benzodiazepines during pregnancy—and equally effective—but there is some controversy about whether SSRIs and TCAs affect preterm delivery and LBW.

• Before prescribing psychotropic drugs to a nursing mother, consider the benefits of breastfeeding to the infant, the severity of the mother's depressive symptoms if left untreated, and the potential risk to the infant of ingestion.

Medicolegal perspective on perinatal depression

Most malpractice cases involving patients with major depressive disorders who subsequently harm themselves or others involve the alleged failure to manage medication dosages or side effects, to appropriately hospitalize the patient, or to heed the warning signs of impending harm. Many of these cases are against psychiatrists, clinics, and occasionally family physicians.

While it is not considered the standard of care for obstetricians to offer mental disorder screening in the office, it is recommended that patients be assessed for psychosocial risk factors, many of which are similar risk factors for perinatal depression. Certainly having a heightened awareness of depressive disorders and making appropriate referrals would be prudent. Given the national media attention to some of the more horrendous cases of perinatal depression in the last few years, it could be possible that a clinician might be considered to have failed a duty to report a patient's known likelihood to harm herself or others.

—Dawn Collins, JD

Ms. Collins is an attorney specializing in medical malpractice in Long Beach, Calif.

 

Kimberly Yonkers, Wendy Brunetto, Megan Smith. Identifying perinatal depression--sooner is better. Contemporary Ob/Gyn Apr. 1, 2004;49:58-81.