Major depression is a common disorder that affects 15 to 25 percent of adults in the United States each year.1 Women are twice as likely as men to experience depression.2,3 Moreover, the peak age of incidence of depression, 18 to 44 years, coincides with the prime childbearing years.4 That women are at increased risk for mood disorders and are particularly vulnerable at times of hormonal fluctuation (i.e., during premenstruum, postpartum and perimenopause3,5,6) suggest that gonadal steroids play an integral role in the pathogenesis of depression in women. Because most patients with depression are treated in primary care practices,7 clinicians providing care to women must be skilled in the detection and treatment of mood disorders in women.
Postpartum major depression (PMD), which occurs in approximately 10 percent of childbearing women,8 may begin anywhere from 24 hours to several months after delivery. When its onset is abrupt and symptoms are severe, women are more likely to seek help early in the illness. In cases with an insidious onset, treatment is often delayed, if it is ever sought. Untreated, PMD may resolve within several months but can linger into the second year postpartum. After the initial episode, women who have had PMD are at risk for both nonpuerperal and puerperal relapses.9,10
Postpartum depression is a traumatic event that can have lasting effects on a woman's confidence in herself as a mother and on her infant's social, emotional and cognitive development.11–16 Infants as young as three months of age are able to detect the affective quality displayed by their mothers and modify their own affective displays in response to it.12–14 Cognitive skills,15 expressive language development16 and attention17 have been adversely affected by maternal depression. These findings emphasize the importance of early detection and treatment of PMD by family physicians, who are well able to intervene on behalf of women and their infants.
Detection of PMD
The detection of PMD is often complicated by several factors. First, most women expect a period of adjustment after having a baby. Therefore, first-time mothers may not recognize that what they are experiencing is not within the norm. Second, societal pressures to be a “good mother” are such that if a woman does recognize that something is wrong, she is loath to admit it out of shame and fear. Moreover, women with PMD frequently think they are “going crazy” and worry that if they share these thoughts with a health care professional, they will be “locked up” or someone will take their baby away from them.
Another complicating factor is that women who did not receive their perinatal care from a family physician are often confused about whom to turn to. They may not be scheduled to see their obstetrician-gynecologist for another year, and their child's pediatrician is identified in their minds as the child's physician.
Physicians may contribute to delayed detection of PMD by minimizing a woman's distress in an effort to be reassuring. Finally, with the pressure of managed care to evaluate more patients in a limited amount of time, psychologic issues frequently receive cursory attention from even the most thoughtful clinicians.
To overcome these significant impediments to the identification of PMD, family physicians should develop formal mechanisms for identifying symptoms of depression in postpartum patients. Such mechanisms include distinguishing PMD from other, similar disorders, identifying patients who are at risk, instituting formal screening and providing educational materials on the disorder.
DISTINGUISHING PMD FROM OTHER DISORDERS
“Postpartum depression” is a clinical term referring to a major depressive episode that is temporally associated with childbirth. Postpartum major depression is not recognized by the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV)18 as being diagnostically distinct from its nonpuerperal counterpart, although the DSM-IV does allow the addition of a postpartum-onset specifier for patients with an onset within four weeks of delivery. Thus, the DSM-IV criteria for diagnosing major depression apply to the diagnosis of PMD as well. However, the similarities between symptoms of depression and the normal sequelae of childbirth often complicate the diagnosis of PMD. The symptoms of major depression are listed in Table 1. Those that are the most difficult to assess in postpartum women are marked with an asterisk.
When trying to determine if the presence of a symptom is a sign of depression or a normal postpartum reaction, the physician should consider the circumstances. A woman's level of exhaustion and irritability when her infant is two weeks old and nursing frequently may not be normal when her baby is four months old and sleeping soundly through the night. The intensity and degree of a woman's coping response may also indicate a pathologic state. Loss of energy and diminished concentration are frequently the result of sleep deprivation. However, for a postpartum woman to have no energy or to have such difficulty in concentrating that she frequently loses her train of thought or has considerable difficulty making decisions is not normal.
Determining how much time has elapsed since delivery helps the physician to distinguish PMD from subclinical mood fluctuations, which occur with such frequency during the first two weeks after delivery that they are considered part of the normal postpartum experience. Many women (range: 26 to 85 percent) experience the “baby blues,” which are characterized by mild depressive symptoms, tearfulness (often for no discernible reason), anxiety, irritability, mood lability, increased sensitivity and fatigue.15,19 The blues typically peak four to five days after delivery, may last hours to days and resolve by the 10th postnatal day.
Although for most women the blues are short-lived, evidence suggests that women who experience them have an increased risk for PMD later in the postpartum period, especially if the blues symptoms were severe.20 Of women who met criteria for PMD six weeks after delivery, two thirds were found to have had the baby blues.21 Similarly, the 10 percent of childbearing women who experience the “highs” (mild euphoria, increased energy) within the first few days of delivery are more likely to be depressed several months later.22 Therefore, subclinical mood swings in either direction after delivery are an indication for more intensive follow-up later in the postpartum period.
Finally, PMD must be distinguished from puerperal psychosis, which occurs in 0.2 percent of childbearing women. Most puerperal psychoses have their onset within the first month of delivery and are manic in nature.18 An inability to sleep for several nights, agitation, expansive or irritable mood and avoidance of the infant are early warning signs heralding the onset of puerperal psychosis. When delusions or hallucinations are present, they often involve the infant. A woman may have thoughts that the baby is possessed by a demon and should die. She may even experience auditory hallucinations “telling” her to kill her infant.18 Because the woman is at risk of harming herself or her baby (or both), postpartum psychosis is a medical emergency. Most patients with puerperal psychosis are treated in a hospital with neuroleptic agents and mood stabilizers.
Before a definitive diagnosis of PMD is made, depression caused by a medical condition such as thyroid dysfunction or anemia must be ruled out. Women who lose an excessive amount of blood during delivery may complain of fatigue as a result of anemia. A host of depressive symptoms such as a “low” mood, a lack of motivation, weight gain, anxiety and fatigue can be symptoms of thyroid dysfunction. About 5 percent of postpartum women have transient hypothyroidism, sometimes preceded by hyperthyroidism,23 during the first year postpartum, and in others, permanent thyroid dysfunction develops.24 Hyperthyroid women may present with rapid weight loss, agitation and panic attacks. Conducting a careful history and physical assessment with appropriate laboratory studies such as thyroid function tests and a complete blood cell count will greatly decrease the risk of misdiagnosis.
IDENTIFYING THOSE AT RISK
In most cases, women who are at risk for PMD can be identified during pregnancy so that appropriate follow-up can be initiated after delivery. Studies have consistently demonstrated that dissatisfaction with the marital relationship and the amount of social support from a spouse and other significant persons increases the risk of PMD.25 As with nonpuerperal depression, stressful life events have been shown to be associated with PMD.26 For example, a woman who is on maternity leave is likely to feel more vulnerable if her husband is laid off from his job than she would if she herself were working full time. Interestingly, complications of labor have not been consistently shown to predict the occurrence of PMD. Some studies have found that obstetric factors increase the risk of PMD,21,27 whereas others have found the opposite association26,28 or no association.20,29 Of 13 studies addressing the role of socioeconomic status in PMD, only two found that low socioeconomic status is predictive of PMD.30
Women who have a previous history of mood disorders, both puerperal and non-puerperal, are at increased risk of relapse after delivery. At least one third of the women who have had PMD have a recurrence of symptoms after a subsequent delivery,31,32 and as many as 60 percent of women with bipolar disorder have a relapse after childbirth.33 Fortunately, identification of these women can be accomplished during the pregnancy with appropriate prenatal screening.
INSTITUTING FORMAL SCREENING
The Edinburgh Postnatal Depression Scale34 is a 10-item, self-rated instrument that has been used to screen for PMD in primary care practices throughout Europe, New Zealand and Australia. A threshold score of 12.5 was shown in one Australian study to detect major depression with a sensitivity of 100 percent and a specificity of 95.5 percent.35 This form can be filled out by patients as they wait in an examination room. With some practice, the instrument can be quickly scored, and a woman who meets a threshold score can be further assessed. Asking a woman to answer questions about how she has been feeling not only causes her to stop and think about herself but also indicates her physician's willingness to hear about her psychologic distress.
PROVIDING EDUCATIONAL MATERIALS
The number of barriers to the detection of PMD emphasizes the need to educate patients and their families about the signs and symptoms of postpartum mood disorders. Support groups such as Depression After Delivery (telephone: 800-944-4PPD) and Postpartum Support International (telephone: 805-967-7636) can either supply or suggest various educational materials that are appropriate for office use. Pamphlets or posters describing the symptoms of depression not only educate patients but also remind them that their physicians are concerned about their emotional health. Providing information about PMD in a visible place in the office may be an invaluable aid for women who do not recognize their feelings or are ashamed of the need to discuss them with their physician. An example of the information that can be shared with patients is included in the patient information handout that follows this article.
Treatment of PMD
Until recently, the treatment of PMD has not been a subject of research because most investigators and clinicians have considered PMD too similar to its nonpuerperal counterpart to warrant such investigation. The most compelling reason that this topic is now being addressed is preclinical and clinical evidence that sex steroids have pronounced effects on the central nervous system, including the areas responsible for mood and cognition.36 Moreover, the observation that women become depressed at twice the rate of men and are particularly vulnerable at times of hormonal fluctuation suggests that depression occurring at such times may be, in part, hormonally driven. Because of this association, several investigators have examined the role of estrogen in the treatment and prophylaxis of PMD. However, results of these studies, which support the hypothesis that puerperal psychiatric disorders may be triggered in part by estrogen withdrawal, must be replicated before estrogen replacement can be recommended in the treatment or prophylaxis of puerperal affective disorders.37,38
In the meantime, despite few controlled studies, the treatment of PMD is based on that of nonpuerperal depression.39–41 Psychotherapy or pharmacotherapy may be used alone or in combination. Because no modality has been shown to be superior to any other, some authors argue that the choice of therapy, pharmacologic and/or psychotherapeutic, for mild to moderate PMD may be left to the patient.41
Because of the relative dearth of information regarding the safety of antidepressant use during lactation, many women may understandably choose a nonpharmacologic form of treatment to avoid exposing their infant to psychotropic medication. Interpersonal therapy is a form of psychotherapy that may be particularly suitable for use in postpartum women because it focuses on the patient's interpersonal relationships and changing roles.42 Marital counseling is warranted when marital conflicts are distressing and perhaps contributing to the woman's depression. At the least, spouses and significant others should be educated about the nature and treatment of PMD and what they can do to find support for themselves and their loved ones during this stressful time.
Although it is arguable that all women with PMD should seek some type of counseling, a woman whose depression is persistent or so severe that she is having difficulty taking care of herself or functioning as a mother, or is having thoughts of harming herself or her child should be evaluated for antidepressant treatment. Frequently, PMD is accompanied by severe anxiety, agitation, or both. Although benzodiazepines may be used to treat anxiety, it is important to consider them as an adjunct to antidepressants because they are not effective in alleviating the core symptoms of depression.
Table 2 summarizes the starting dosages, typical therapeutic dosing range and most common side effects of antidepressants frequently prescribed for major depression. Monoamine oxidase inhibitors are not included in the table; because of strict dietary constraints and the possible risk for a hypertensive crisis, these agents are no longer considered a first-line treatment in patients with major depression. Tricyclic antidepressants (imipramine [Tofranil], desipramine [Norpramin], amitriptyline [Elavil] and nortriptyline [Pamelor]) have probably been prescribed most frequently for puerperal and nonpuerperal depression. Selective serotonin reuptake inhibitors (SSRIs) may be better tolerated and have the advantage of once-a-day dosing.
Starting and typical therapeutic dosages of antidepressants are given in Table 2. Women with PMD should remain on the initial dosage of antidepressant for about two weeks before the dosage is increased. Most patients show signs of clinical improvement within two to four weeks of starting the medication. If no improvement occurs or the patient is deteriorating after two weeks of treatment, the initial dosage should be increased, with further increases occurring no sooner than every seven days. In uncomplicated PMD, clinical improvement should be obtained within six to eight weeks of the start of antidepressant treatment. Patients who are decompensating despite higher dosages of medication or who do not respond adequately to a medication trial should be referred to a psychiatrist for a psychopharmacologic evaluation.
|Drug*||Starting dosage (mg/day)||Usual daily dosage (mg/day)†||Half-life (hours)||Side effects||Cost (generic)‡|
|Amitriptyline (Elavil)||25 to 75||100 to 200||21||Constipation, sedation, weight gain, orthostatic hypotension, blurred vision, dry mouth||$37.00 (3.00 to 6.00)|
|Desipramine (Norpramin)||25 to 75||150 to 200||22||Same as with amitriptyline||89.00 (35.00 to 66.00)|
|Imipramine pamoate (Tofranil-PM)||25 to 75||150 to 200||25||Same as with amitriptyline||72.00 (4.00 to 8.00)|
|Nortriptyline (Pamelor)||25||75 to 100||32||Same as with amitriptyline||86.00 (66.00 to 71.00)|
|Clomipramine (Anafranil)||50||150 to 200||19 to 37||Same as with amitriptyline||68.00|
|Selective serotonin reuptake inhibitors|
|Fluoxetine (Prozac)||20||20 to 40||60 (60 to 384, norfluoxetine)||Headache, nausea, diarrhea, nervousness, sedation, insomnia, Tremor||73.00|
|Sertraline (Zoloft)||50||50 to 150||26||Same as with fluoxetine||65.00|
|Fluvoxamine (Luvox)||50||100 to 300||15||Same as with fluoxetine||64.00|
|Paroxetine (Paxil)||20||20 to 40||26||Same as with fluoxetine||62.00|
|Bupropion (Wellbutrin)||200||200 to 300||8 to 12||Generalized seizures§ (0.4 percent), agitation, dry mouth, sweating||49.00|
|Venlafaxine (Effexor)||75||75 to 225||3 to 7||Sustained hypertension, nervousness, insomnia, anorexia||34.00|
|Nefazodone (Serzone)||200||300 to 600||2 to 4||Priapism,§ orthostatic hypotension, somnolence, dry mouth, nausea||58.00|
|Mirtazapine (Remeron)||15||15 to 45||20 to 40||Agranulocytosis,§ somnolence, nausea, weight gain, increased cholesterol/triglyceride level||59.00|
Data are lacking regarding the optimal duration of treatment of PMD. A conservative estimate would be nine to 12 months of antidepressant therapy if the woman is experiencing her first episode of major depression.
Determining the duration of antidepressant treatment required to prevent the relapse of PMD would be particularly helpful for breast-feeding women because the American Academy of Pediatrics recommends that infants be breast-fed in their first year of life.43
The use of antidepressants during breast feeding has been extensively reviewed.44 In most cases, infant blood concentrations of tricyclic antidepressants and SSRIs have been below the detection limit of commercial laboratories.44 Evidence shows, however, that antidepressants and their metabolites are passed on to infants through breast milk and that detectable levels of these are found in the plasma of some infants.45–50 In most cases, these infants tolerated the exposure without difficulties.45,46,51
To summarize treatment recommendations: first, most women with PMD benefit from supportive individual or group therapy. Women with severe marital discord should be referred for couples therapy.
Second, the use of tricyclic antidepressants and SSRIs is not contraindicated during breast feeding and should be seriously considered in lactating and nonlactating women who have moderate to severe PMD, suicidal thoughts or difficulty functioning, or who have not responded to supportive therapy alone. In such patients, the benefits of taking an antidepressant will probably outweigh the risks of infant psychotropic exposure. However, women should make informed decisions that are documented in their medical records. Whenever possible, husbands and significant others should be included in the decision to expose or not expose the infant to an antidepressant drug.
Third, antidepressant treatment should be initiated at the usual starting dosage. The dosage can be increased after sufficient time to assess therapeutic benefit and side effects.
Fourth, because of the long elimination half-life of fluoxetine (Prozac), if a woman who was taking this drug during pregnancy wishes to breast feed while continuing fluoxetine treatment, she should have the infant's blood tested after about six weeks of breast feeding to rule out drug accumulation. In infants exposed to any antidepressant through breast milk, plasma concentrations of the drug should be determined if they are exhibiting persistent unexplained irritability.
Finally, any woman who is severely depressed, is having suicidal or infanticidal ideation or has not responded to an adequate antidepressant trial should be referred to a psychiatrist for further evaluation and treatment. Symptoms of psychosis are an indication for emergency psychiatric evaluation.