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Treatment in Psychiatry   |    
Antidepressant Use in the Postpartum Period: Practical Considerations
Jennifer L. Payne, M.D.
Am J Psychiatry 2007;164:1329-1332. doi:10.1176/appi.ajp.2007.07030390

A 30-year-old woman, 6 weeks postpartum, is referred by her obstetrician for possible postpartum depression. The patient noted onset of symptoms 2 days after delivery of her son; describing the onset, she said she felt as if “a curtain descended upon” her. Her symptoms include low mood, tearfulness, decreased sleep and appetite, significant weight loss, and anhedonia. She feels she cannot care for her son properly and has intrusive thoughts that some unspecified harm may come to him. She adamantly denies thoughts of hurting herself or her son but worries constantly that “something bad will happen.” At night, she feels restless and frequently checks that the baby is still breathing. Her concentration is poor, and she often does not shower or take care of household duties, but she does care for her son. On examination, the patient appears sad and anxious, with psychomotor retardation. She denies a previous psychiatric history. Her family history is notable for bipolar I disorder in a paternal uncle and a grandfather. She is breastfeeding. A 27-year-old woman with a history of recurrent major depression since age 18 presents for a consultation during her second trimester of pregnancy. The patient has a history of nonresponse to selective serotonin reuptake inhibitors (SSRIs) and has been hospitalized twice for severe depressive episodes. During the second hospitalization, at age 25, she required six ECT treatments. Since that time, she has been maintained with good results on 75 mg daily of nortriptyline. Her treating psychiatrist recommended that she continue taking the nortriptyline during the pregnancy, which she has done. The patient is now seeking consultation and recommendations regarding breastfeeding after delivery.

These clinical vignettes demonstrate just a few of the complexities of treating women with mood disorders during the childbearing years. Much attention has been given to the treatment of women with mood disorders during pregnancy. Less, however, has been focused on the treatment of such women during the postpartum period, although many of the clinical issues are the same—including the fact that if the patient is breastfeeding, the treating psychiatrist has two patients to consider, not just one. This review covers the treatment of new-onset and existing mood disorders during the postpartum period; postpartum depression in bipolar disorder; the implications of breastfeeding while taking psychiatric medications; and nonpharmacological interventions.

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Postpartum Mood Disorders

Three types of postpartum mood disorders are described in the literature: postpartum blues, postpartum depression, and postpartum psychosis. Postpartum blues is a relatively common phenomenon occurring in up to 80% of women, generally within a few days after delivery. It is self-limited, resolving over several days. Symptoms include tearfulness, mood lability, and a feeling of being overwhelmed (1). Postpartum depression, which is less common, occurring in 10%–20% of women, meets DSM-IV criteria for a major depressive episode, lasting at least 2 weeks (2). The risk of postpartum depression is higher in women with a history of major depression (3) or postpartum depression following a previous pregnancy (4). While the etiology of postpartum depression is unknown, it is very likely multifactorial, with psychological factors, biological factors including hormonal changes, and social factors, such as poor social support and stressful life events, all playing a role. Postpartum psychosis is rare, occurring in approximately 0.1% of all deliveries. It is more common in women with bipolar disorder, and it resembles a manic or mixed episode, with decreased sleep, psychosis, and agitation. The treatment of postpartum psychosis is beyond the scope of this review (see reference 5 for a review).

DSM-IV allows the specification of “postpartum onset” for depressive, manic, or mixed episodes occurring within 4 weeks of delivery but does not use the categories described above. The onset of postpartum depression can, of course, occur beyond 4 weeks, and up to 1 year, after delivery. Although later-onset episodes do not meet DSM-IV criteria for a postpartum specification, they have many, if not all, features and issues in common with those occurring within 4 weeks, and the considerations outlined below apply equally to them.

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Effect of Postpartum Depression on Children

Postpartum depression has been shown to have deleterious consequences for the infants and children of affected mothers (6). Impaired bonding during this critical time has been linked to attachment insecurity in the child. Other studies show impaired emotional development, language development, attention, and cognitive skills in children of depressed mothers, and these children are more likely to develop long-term behavioral problems. In short, impairment in the mother can lead to impairment in the children. Thus, exposure of a child to postpartum depression should be considered an exposure in the same way that taking an antidepressant while breastfeeding is an exposure. The risks of exposure to postpartum depression appear to outweigh at least the short-term risks of exposure to antidepressants during breastfeeding, although more research is needed, particularly long-term studies, to firmly support this statement. The identification, treatment, and prevention of postpartum depression are of paramount importance to ensure the well-being of both mothers and their children.

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Prevention and Treatment: Medications

Surprisingly few randomized trials have been conducted to examine prevention of recurrent postpartum depression. Two placebo-controlled trials have been conducted on the prevention of recurrent postpartum depression, one using nortriptyline in 26 women (7) and the other using sertraline in 14 women (8). Nortriptyline failed to decrease the rate of postpartum depression while sertraline succeeded, although the nortriptyline study may have been underpowered. In a double-blind study of fluoxetine versus placebo plus one or six sessions of counseling, Appleby et al. (9) found that significantly more women in the fluoxetine group improved compared with the placebo group, and no significant interaction with therapy was observed. Wisner et al., in a double-blind trial comparing sertraline and nortriptyline, found no differences between medications in rates of response or remission, with 46%–48% remitting and 56%–69% responding by week 8 of treatment (10).

A number of open-label studies have supported the use of antidepressants to treat postpartum depression, including sertraline (11), paroxetine (12), bupropion (13), venlafaxine (14), and fluvoxamine (15). Other clinical trials include a randomized double-blind trial of T4 in thyroid antibody-positive women, which was negative (16), and an open-label study of omega-3 fatty acids, which showed a significant response rate (17). Several studies have been conducted on the use of estrogen in either preventing the onset of postpartum depression or in treating depressive symptoms in the postpartum period. The potential medical complications of using estrogen limit the clinical usefulness of these trials.

In general, although more research needs to be done, one can assume that the treatment of postpartum depression is similar to the treatment of depression at any other time. To date, there is no consistent evidence that any one class of antidepressants is superior. The treatment and prevention of postpartum depression may thus be dictated by the patient’s prior response to medications. The choice of whether to use an antidepressant and, if so, which one to use may also be affected by the patient’s views on medication use during pregnancy and whether she plans to breastfeed her baby (see below).

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Postpartum Depression and Bipolar Disorder

Few studies have examined the rates of postpartum depression in women with bipolar disorder. Freeman et al. (18) found that 67% of 30 women with bipolar disorder experienced a postpartum mood episode within 1 month of childbirth, and most were depressive episodes. In this sample, the recurrence rate of postpartum depression was 100% in the eight women who had experienced episodes in previous pregnancies. In a larger sample, Payne et al. (19) found that approximately 20% of women with bipolar disorder retrospectively report significant postpartum mood changes, most of which were depressive episodes. Thus, postpartum depression is relatively common in women with bipolar disorder. It remains unclear what proportion of women presenting with a first episode of postpartum depression will have symptoms that progress to a bipolar diagnosis, although a family history of bipolar disorder may be the strongest predictor (20).

Women with no history of mood disorder who present with a new-onset postpartum depression should be screened for personal and family histories of hypomania or mania. It is important to provide education about the signs and symptoms of hypomania and mania, since antidepressant treatment may trigger the onset of such symptoms, which should be addressed promptly (20). Whenever possible, the patient’s spouse or significant other should also be interviewed and educated about such symptoms. Women with a family history of bipolar disorder should be followed closely to monitor for the development of hypomanic or manic symptoms, and appropriate treatment with mood stabilizers should be instituted if such symptoms emerge.

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Antidepressants and Breastfeeding

The benefits of breastfeeding for the baby are well documented. The American Academy of Pediatrics advocates breastfeeding through the first 6 months of life. Most psychotropic medications pass readily into breast milk. In general, however, studies have not found high rates of adverse events in infants exposed to antidepressants, including tricyclics and SSRIs (21, 22). It has been recommended (22) that fluoxetine (which has a long half-life) and high doses of citalopram (which has high breast milk and plasma concentrations) be used with caution during breastfeeding and only in patients who had good results with these medications during pregnancy or a previous episode. Most reports show few adverse events and low or undetectable plasma levels with sertraline, paroxetine, and fluvoxamine (21, 22). Although a few cases reports have appeared with positive outcomes with venlafaxine, trazodone, and bupropion, it is too soon to draw firm conclusions (22). There have been no reports to date on the safety of escitalopram. Although rates of adverse events are low, the serum concentration of antidepressant in the infant can vary widely, and the long-term outcome of infants exposed during breastfeeding is unknown. It is known, however, that with most antidepressants, infant drug exposure is generally higher through placental passage than through breast milk (22). Thus, if a woman has taken a medication during pregnancy, it makes sense to continue with that medication during breastfeeding to minimize the number of medications to which the infant is exposed.

General clinical recommendations for mothers include taking the antidepressant immediately after breastfeeding and prior to the infant’s sleep time to minimize exposure to peak drug concentrations (21). Mother and infant serum concentrations can be monitored and formula preparations used during peak serum concentrations, although this may not always be practical. Mothers and family members should be educated about the potential side effects of any medication prescribed during breastfeeding. Involvement of the pediatrician is highly recommended, and routine clinical monitoring of the infant for adverse effects, such as sedation, changes in sleep or feeding, and irritability, should be instituted (21).

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Nonpharmacological Management

A number of studies using psychosocial or psychological interventions in the prevention or treatment of postpartum depression have been conducted. A recent Cochrane review (23) concluded that because of methodological problems, heterogeneous samples, and low participation rates, there was insufficient evidence to recommend any of these approaches for the prevention of postpartum depression. Some interventions, such as cognitive behavior therapy and interpersonal psychotherapy, have been better studied in the treatment of postpartum depression and depression in general and therefore may be useful in patients with postpartum depression and should be considered as part of the treatment plan.

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Summary and Recommendations

Although the research data on the use of antidepressants during the postpartum period are relatively sparse, a number of clinical recommendations can be made. Risks to the mother as well as to the baby must be considered, just as during pregnancy. These risks include those of treatment of the depression, including antidepressant exposure, as well as those of not treating the depression, which include the risk of depression to the mother, poor bonding between mother and child, and possible effects on IQ, language, and development in the child. Antidepressant treatment during breastfeeding can be an appropriate choice, although the child will be exposed to the antidepressant in breast milk. One should keep in mind that if the mother took antidepressants during pregnancy, the child has already been exposed to the medication, and it remains unclear whether there is an additional risk to the child in continuing that exposure during breastfeeding. Finally, the possible diagnosis of bipolar disorder should always be kept in mind in a new-onset postpartum depression, as antidepressant treatment can precipitate a manic episode.

Perhaps the most important clinical recommendation to psychiatrists treating women with mood disorders during childbearing is to use a team approach. The husband or significant other should be educated about the potential risks and benefits of treatment, and when appropriate, other members of the patient’s family should be included as well. The patient’s obstetrician should be advised of treatments that occur during pregnancy, and the child’s pediatrician should be involved in clinical decision making. A team approach is likely to improve outcomes and provide more consistent support to the mother as she makes difficult choices about her own health and the health of her baby.

In the first vignette presented earlier, the patient presented with postpartum depression. Her symptoms were severe enough that they were interfering with her ability to care for herself and her household. She had never experienced psychiatric symptoms previously but had a family history of bipolar disorder. Treatment in this case included educating the patient about depression and postpartum depression as well as bipolar disorder, given that her course of illness could evolve into this disorder. A trial of an antidepressant was recommended. Because the patient’s child had not been exposed to antidepressants during pregnancy, the patient was encouraged to consider whether she wished to continue breastfeeding while taking an antidepressant and was given all available information about the recommended antidepressant. Her husband was involved in the treatment plan and was educated about depression, symptoms of emerging bipolar disorder, and psychiatric treatment. The patient chose to continue breastfeeding and was started on sertraline and followed closely for the next several weeks, while the pediatrician monitored the baby.

In the second vignette, the patient sought advice about treatment during the postpartum period and during breastfeeding. She had a history of severe major depression and was maintained on nortriptyline during her pregnancy. She was educated about her risk of postpartum depression and the need for continued treatment after delivery. Despite the lack of evidence that nortriptyline prevents the onset of postpartum depression, given the patient’s response to it, it was recommended that the nortriptyline be continued and that the patient be followed closely during the postpartum period. The patient was given all available information about the use of nortriptyline during breastfeeding. Her baby’s future pediatrician was contacted and the risks to the baby discussed. In this case, although the baby had already been exposed to the antidepressant in utero, the patient decided not to breastfeed. Her husband, whom the consulting psychiatrist had also educated about the risks and benefits, agreed with and supported this decision.

+Received March 2, 2007; revision received May 11, 2007; accepted May 14, 2007 (doi: 10.1176/appi.ajp.2007.07030390). From the Department of Psychiatry, Johns Hopkins University, Baltimore. Address correspondence and reprint requests to Dr. Payne, Johns Hopkins School of Medicine, 600 N. Wolfe St., Meyer 3-181, Baltimore, MD 21287; jpayne5@jhmi.edu (e-mail).

+CME Disclosure: Dr. Payne reports research support from NIH, the Stanley Medical Research Institute, and Novartis and a speaking honorarium from AstraZeneca.

+APA policy requires disclosure by CME authors of unapproved or investigational use of products discussed in CME programs. Off-label use of medications by individual physicians is permitted and common. Decisions about off-label use can be guided by scientific literature and clinical experience.

1.Payne JL: The role of estrogen in mood disorders in women. Int Rev Psychiatry 2003; 15:280–290
 
2.Campbell SB, Cohn JF: Prevalence and correlates of postpartum depression in first-time mothers. J Abnorm Psychol 1991; 100:594–599
 
3.Frank E, Kupfer DJ, Jacob M, Blumenthal SJ, Jarrett DB: Pregnancy-related affective episodes among women with recurrent depression. Am J Psychiatry 1987; 144:288–293
 
4.Cox JL, Murray D, Chapman G: A controlled study of the onset, duration, and prevalence of postnatal depression. Br J Psychiatry 1993; 163:27–31
 
5.Sit D, Rothschild AJ, Wisner KL: A review of postpartum psychosis. J Womens Health (Larchmt) 2006; 15:352–368
 
6.Grace SL, Evindar A, Stewart DE: The effect of postpartum depression on child cognitive development and behavior: a review and critical analysis of the literature. Arch Womens Ment Health 2003; 6:263–274
 
7.Wisner KL, Perel JM, Peindl KS, Hanusa BH, Findling RL, Rapport D: Prevention of recurrent postpartum depression: a randomized clinical trial. J Clin Psychiatry 2001; 62:82–86
 
8.Wisner KL, Perel JM, Peindl KS, Hanusa BH, Piontek CM, Findling RL: Prevention of postpartum depression: a pilot randomized clinical trial. Am J Psychiatry 2004; 161:1290–1292
 
9.Appleby L, Warner R, Whitton A, Faragher B: A controlled study of fluoxetine and cognitive-behavioural counselling in the treatment of postnatal depression. BMJ 1997; 314:932–936
 
10.Wisner KL, Hanusa BH, Perel JM, Peindl KS, Piontek CM, Sit DK, Findling RL, Moses-Kolko EL: Postpartum depression: a randomized trial of sertraline versus nortriptyline. J Clin Psychopharmacol 2006; 26:353–360
 
11.Stowe ZN, Nemeroff CB: Women at risk for postpartum-onset major depression. Am J Obstet Gynecol 1995; 173:639–645
 
12.Misri S, Reebye P, Corral M, Milis L: The use of paroxetine and cognitive-behavioral therapy in postpartum depression and anxiety: a randomized controlled trial. J Clin Psychiatry 2004; 65:1236–1241
 
13.Nonacs RM, Soares CN, Viguera AC, Pearson K, Poitras JR, Cohen LS: Bupropion SR for the treatment of postpartum depression: a pilot study. Int J Neuropsychopharmacol 2005; 8:445–449
 
14.Cohen LS, Viguera AC, Bouffard SM, Nonacs RM, Morabito C, Collins MH, Ablon JS: Venlafaxine in the treatment of postpartum depression. J Clin Psychiatry 2001; 62:592–596
 
15.Suri R, Burt VK, Altshuler LL, Zuckerbrow-Miller J, Fairbanks L: Fluvoxamine for postpartum depression (letter). Am J Psychiatry 2001; 158:1739–1740
 
16.Harris B, Oretti R, Lazarus J, Parkes A, John R, Richards C, Newcombe R, Hall R: Randomised trial of thyroxine to prevent postnatal depression in thyroid-antibody-positive women. Br J Psychiatry 2002; 180:327–330
 
17.Freeman MP, Hibbeln JR, Wisner KL, Brumbach BH, Watchman M, Gelenberg AJ: Randomized dose-ranging pilot trial of omega-3 fatty acids for postpartum depression. Acta Psychiatr Scand 2006; 113:31–35
 
18.Freeman MP, Smith KW, Freeman SA, McElroy SL, Kmetz GE, Wright R, Keck PE Jr: The impact of reproductive events on the course of bipolar disorder in women. J Clin Psychiatry 2002; 63:284–287
 
19.Payne JL, Roy PS, Murphy-Eberenz K, Weismann MM, Swartz KL, McInnis MG, Nwulia E, Mondimore FM, MacKinnon DF, Miller EB, Nurnberger JI, Levinson DF, DePaulo JR Jr, Potash JB: Reproductive cycle-associated mood symptoms in women with major depression and bipolar disorder. J Affect Disord 2007; 99:221–229
 
20.Sharma V: A cautionary note on the use of antidepressants in postpartum depression. Bipolar Disord 2006; 8:411–414
 
21.Burt VK, Suri R, Altshuler L, Stowe Z, Hendrick VC, Muntean E: The use of psychotropic medications during breast-feeding. Am J Psychiatry 2001; 158:1001–1009
 
22.Eberhard-Gran M, Eskild A, Opjordsmoen S: Use of psychotropic medications in treating mood disorders during lactation: practical recommendations. CNS Drugs 2006; 20:187–198
 
23.Dennis CL, Creedy D: Psychosocial and psychological interventions for preventing postpartum depression. Cochrane Database Syst Rev 2004; 18:CD001134
 
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References

1.Payne JL: The role of estrogen in mood disorders in women. Int Rev Psychiatry 2003; 15:280–290
 
2.Campbell SB, Cohn JF: Prevalence and correlates of postpartum depression in first-time mothers. J Abnorm Psychol 1991; 100:594–599
 
3.Frank E, Kupfer DJ, Jacob M, Blumenthal SJ, Jarrett DB: Pregnancy-related affective episodes among women with recurrent depression. Am J Psychiatry 1987; 144:288–293
 
4.Cox JL, Murray D, Chapman G: A controlled study of the onset, duration, and prevalence of postnatal depression. Br J Psychiatry 1993; 163:27–31
 
5.Sit D, Rothschild AJ, Wisner KL: A review of postpartum psychosis. J Womens Health (Larchmt) 2006; 15:352–368
 
6.Grace SL, Evindar A, Stewart DE: The effect of postpartum depression on child cognitive development and behavior: a review and critical analysis of the literature. Arch Womens Ment Health 2003; 6:263–274
 
7.Wisner KL, Perel JM, Peindl KS, Hanusa BH, Findling RL, Rapport D: Prevention of recurrent postpartum depression: a randomized clinical trial. J Clin Psychiatry 2001; 62:82–86
 
8.Wisner KL, Perel JM, Peindl KS, Hanusa BH, Piontek CM, Findling RL: Prevention of postpartum depression: a pilot randomized clinical trial. Am J Psychiatry 2004; 161:1290–1292
 
9.Appleby L, Warner R, Whitton A, Faragher B: A controlled study of fluoxetine and cognitive-behavioural counselling in the treatment of postnatal depression. BMJ 1997; 314:932–936
 
10.Wisner KL, Hanusa BH, Perel JM, Peindl KS, Piontek CM, Sit DK, Findling RL, Moses-Kolko EL: Postpartum depression: a randomized trial of sertraline versus nortriptyline. J Clin Psychopharmacol 2006; 26:353–360
 
11.Stowe ZN, Nemeroff CB: Women at risk for postpartum-onset major depression. Am J Obstet Gynecol 1995; 173:639–645
 
12.Misri S, Reebye P, Corral M, Milis L: The use of paroxetine and cognitive-behavioral therapy in postpartum depression and anxiety: a randomized controlled trial. J Clin Psychiatry 2004; 65:1236–1241
 
13.Nonacs RM, Soares CN, Viguera AC, Pearson K, Poitras JR, Cohen LS: Bupropion SR for the treatment of postpartum depression: a pilot study. Int J Neuropsychopharmacol 2005; 8:445–449
 
14.Cohen LS, Viguera AC, Bouffard SM, Nonacs RM, Morabito C, Collins MH, Ablon JS: Venlafaxine in the treatment of postpartum depression. J Clin Psychiatry 2001; 62:592–596
 
15.Suri R, Burt VK, Altshuler LL, Zuckerbrow-Miller J, Fairbanks L: Fluvoxamine for postpartum depression (letter). Am J Psychiatry 2001; 158:1739–1740
 
16.Harris B, Oretti R, Lazarus J, Parkes A, John R, Richards C, Newcombe R, Hall R: Randomised trial of thyroxine to prevent postnatal depression in thyroid-antibody-positive women. Br J Psychiatry 2002; 180:327–330
 
17.Freeman MP, Hibbeln JR, Wisner KL, Brumbach BH, Watchman M, Gelenberg AJ: Randomized dose-ranging pilot trial of omega-3 fatty acids for postpartum depression. Acta Psychiatr Scand 2006; 113:31–35
 
18.Freeman MP, Smith KW, Freeman SA, McElroy SL, Kmetz GE, Wright R, Keck PE Jr: The impact of reproductive events on the course of bipolar disorder in women. J Clin Psychiatry 2002; 63:284–287
 
19.Payne JL, Roy PS, Murphy-Eberenz K, Weismann MM, Swartz KL, McInnis MG, Nwulia E, Mondimore FM, MacKinnon DF, Miller EB, Nurnberger JI, Levinson DF, DePaulo JR Jr, Potash JB: Reproductive cycle-associated mood symptoms in women with major depression and bipolar disorder. J Affect Disord 2007; 99:221–229
 
20.Sharma V: A cautionary note on the use of antidepressants in postpartum depression. Bipolar Disord 2006; 8:411–414
 
21.Burt VK, Suri R, Altshuler L, Stowe Z, Hendrick VC, Muntean E: The use of psychotropic medications during breast-feeding. Am J Psychiatry 2001; 158:1001–1009
 
22.Eberhard-Gran M, Eskild A, Opjordsmoen S: Use of psychotropic medications in treating mood disorders during lactation: practical recommendations. CNS Drugs 2006; 20:187–198
 
23.Dennis CL, Creedy D: Psychosocial and psychological interventions for preventing postpartum depression. Cochrane Database Syst Rev 2004; 18:CD001134
 
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1.
The strongest predictor that women with postpartum depression will ultimately develop bipolar disorder is which of the following?
2.
Compared to breast milk exposure, infant drug exposure through placental passage has which of the following characteristics?
3.
Postpartum depression (meeting DSM-IV major depressive episode definition) occurs in what percent of women following delivery?
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