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Objective: Postpartum major depression is a significant public health problem that strikes 15% of new mothers and confers adverse consequences for mothers, children, and families. The neural mechanisms involved in postpartum depression remain unknown, but brain processing of affective stimuli appears to be involved in other affective disorders. The authors examined activity in response to negative emotional faces in the dorsomedial prefrontal cortex and amygdala, key emotion regulatory neural regions of importance to both mothering and depression. Method: Postpartum healthy mothers (N=16) and unmedicated depressed mothers (N=14) underwent functional magnetic resonance imaging blood-oxygen-level-dependent acquisition during a block-designed face versus shape matching task. A two-way analysis of variance was performed examining main effects of condition and group and group-by-condition interaction on activity in bilateral dorsomedial prefrontal cortical and amygdala regions of interest. Results: Depressed mothers relative to healthy mothers had significantly reduced left dorsomedial prefrontal cortical face-related activity. In depressed mothers, there was also a significant negative correlation between left amygdala activity and postpartum depression severity and a significant positive correlation between right amygdala activity and absence of infant-related hostility. There was reliable top-down connectivity from the left dorsomedial prefrontal cortex to the left amygdala in healthy, but not depressed, mothers. Conclusions: Significantly diminished dorsomedial prefrontal cortex activity and dorsomedial prefrontal cortical-amygdala effective connectivity in response to negative emotional faces may represent an important neural mechanism, or effect, of postpartum depression. Reduced amygdala activity in response to negative emotional faces is associated with greater postpartum depression severity and more impaired maternal attachment processes in postpartum depressed mothers. doi: 10.1176/appi.ajp.2010.09081235

Objective: Selective serotonin reuptake inhibitor (SSRI) use during pregnancy incurs a low absolute risk for major malformations; however, other adverse outcomes have been reported. Major depression also affects reproductive outcomes. This study examined whether 1) minor physical anomalies, 2) maternal weight gain and infant birth weight, 3) preterm birth, and 4) neonatal adaptation are affected by SSRI or depression exposure. Method: This prospective observational investigation included maternal assessments at 20, 30, and 36 weeks of gestation. Neonatal outcomes were obtained by blinded review of delivery records and infant examinations. Pregnant women (N=238) were categorized into three mutually exclusive exposure groups: 1) no SSRI, no depression (N=131); 2) SSRI exposure (N=71), either continuous (N=48) or partial (N=23); and 3) major depressive disorder (N=36), either continuous (N=14) or partial (N=22). The mean depressive symptom level of the group with continuous depression and no SSRI exposure was significantly greater than for all other groups, demonstrating the expected treatment effect of SSRIs. Main outcomes were minor physical anomalies, maternal weight gain, infant birth weight, pregnancy duration, and neonatal characteristics. Results: Infants exposed to either SSRIs or depression continuously across gestation were more likely to be born preterm than infants with partial or no exposure. Neither SSRI nor depression exposure increased risk for minor physical anomalies or reduced maternal weight gain. Mean infant birth weights were equivalent. Other neonatal outcomes were similar, except 5-minute Apgar scores. Conclusions: For depressed pregnant women, both continuous SSRI exposure and continuous untreated depression were associated with preterm birth rates exceeding 20%.

Objective: The purpose of this study was to assess the evidence base for the efficacy of light therapy in treating mood disorders. Method: The authors systematically searched PubMed (January 1975 to July 2003) to identify randomized, controlled trials of light therapy for mood disorders that fulfilled predefined criteria. These articles were abstracted, and data were synthesized by disease and intervention category. Results: Only 13% of the studies met the inclusion criteria. Meta-analyses revealed that a significant reduction in depression symptom severity was associated with bright light treatment (eight studies, having an effect size of 0.84 and 95% confidence interval [CI] of 0.60 to 1.08) and dawn simulation in seasonal affective disorder (five studies; effect size=0.73, 95% CI=0.37 to 1.08) and with bright light treatment in nonseasonal depression (three studies; effect size=0.53, 95% CI=0.18 to 0.89). Bright light as an adjunct to antidepressant pharmacotherapy for nonseasonal depression was not effective (five studies; effect size= -0.01, 95% CI=0.36 to 0.34). Conclusions: Many reports of the efficacy of light therapy are not based on rigorous study designs. This analysis of randomized, controlled trials suggests that bright light treatment and dawn simulation for seasonal affective disorder and bright light for nonseasonal depression are efficacious, with effect sizes equivalent to those in most antidepressant pharmacotherapy trials. Adopting standard approaches to light therapy's specific issues (e.g., defining parameters of active versus placebo conditions) and incorporating rigorous designs (e.g., adequate group sizes, randomized assignment) are necessary to evaluate light therapy for mood disorders.

Objective: The available data on antidepressant levels in nursing infants were analyzed in order to calculate average infant drug levels and determine what factors influence plasma drug levels in breastfeeding infants of mothers treated with antidepressants. Method: Electronic searches of MEDLINE, PreMEDLINE, Current Contents, Biological Abstracts, and PsycINFO from 1966 through July 2002 followed by bibliographic searches identified 67 relevant studies (two unpublished). By consensus the authors identified 57 studies of maternal plasma, breast milk, and/or infant plasma antidepressant levels from nursing mother-infant pairs, measured by liquid chromatography. Results: Infants with recent prenatal exposure and symptomatic infants included in case reports were analyzed separately. Infant plasma levels were standardized against the average maternal level for each drug. The average infant-maternal plasma ratio was calculated for each drug, and correlations of infant plasma level to maternal dose, maternal plasma level, and breast milk level were calculated. Nortriptyline, paroxetine, and sertraline usually produce undetectable infant levels. Of drugs currently used, fluoxetine produces the highest proportion (22%) of infant levels that are elevated above 10% of the average maternal level. Based on smaller numbers, the data on citalopram indicate that it produces elevated levels in 17% of infants. The milk-to-plasma ratios for 11 antidepressants had a statistically significant negative association with the percentage of the drug bound to protein. Conclusions: Nortriptyline, paroxetine, and sertraline may be preferred choices in breast-feeding women. Minimizing the maternal dose may be helpful with citalopram. Current data do not support monitoring breast milk levels in individual patients. Future researchers should report maternal, breast milk, and infant antidepressant levels along with other appropriate variables.

Objective: Bipolar disorder affects 0.5%-1.5% of individuals in the United States. The typical age at onset is late adolescence or early adulthood, placing women at risk for episodes throughout their reproductive years. General guidelines for the treatment of bipolar disorder are available from the American Psychiatric Association, but additional issues arise when these guidelines are applied in the treatment of peripartum women. The authors summarize knowledge regarding the management of bipolar disorder during pregnancy and the postpartum period, with a focus on managing mania, hypomania, and the psychotic components of the illness. Method: An expert panel reviewed articles that address the management of bipolar disorder and the consequences of the use of mood stabilizers during pregnancy, and a consensus document was generated. Results: The treatment of bipolar disorder in pregnant women involves significant challenges. Some mood stabilizers, e.g., sodium valproate and carbamazepine, are human teratogens. On the other hand, the teratogenicity associated with lithium may have been overestimated in the past. Conclusions: Since treatment can be managed most effectively if pregnancy is planned, clinicians should discuss the issue of pregnancy and its management with every bipolar disorder patient who has childbearing potential, regardless of future reproductive plans. Additional research should address the risks of disturbed sleep to pregnant and postpartum women with bipolar disorder, as well as structural and behavioral consequences to offspring when mood stabilizers are used during pregnancy. Longitudinal and cohort studies can promote these efforts. Given the rate of bipolar disorder in the general population, research efforts will need to be broad based and include multiple collaborating centers.

Objective: About 5% of pregnant women meet criteria for major depression. No pharmacotherapy is specifically approved for antepartum depression; novel treatment approaches may be welcome. The authors explored the use of morning bright light therapy for antepartum depression. Method: An open trial of bright light therapy in an A-B-A design was conducted for 3-5 weeks in 16 pregnant patients with major depression. The Hamilton Depression Rating Scale, Seasonal Affective Disorders Version, was administered to assess changes in mood. A follow-up questionnaire was used to assess outcome after delivery. Results: After 3 weeks of treatment, mean depression ratings improved by 49%. Benefits were seen through 5 weeks of treatment. There was no evidence of adverse effects of light therapy on pregnancy. Conclusions: These data provide evidence that morning light therapy has an antidepressant effect during pregnancy. A randomized controlled trial is warranted to test this alternative to medication.

New mothers who want to nurse their babies should avoid taking the antidepressant drug fluoxetine. A 32-year-old woman with manic-depression took fluoxetine, carbamazepine and buspirone throughout her pregnancy. When the child was born, her doctor advised her not to breastfeed her baby. She began breastfeeding while continuing to take the drugs. The child experienced several seizures according to the mother, but neurologic evaluations were normal. Blood samples from mother and baby as well as breast milk samples were analyzed and revealed significant amounts of fluoxetine.

Objective: The primary purpose of this article is to review critically the literature about use of antidepressants during lactation. Strategies for the clinical management of depressed breast-feeding mothers are also suggested. Method: The authors conducted a computerized search of MEDLINE for articles. The review includes studies in which serum levels of drugs were obtained from nursing infants. Results: Fifteen published reports were located that provided information for the following nine antidepressants: amitriptyline, nortriptyline, desipramine, clomipramine, doxepin, dothiepin, fluoxetine, sertraline, and bupropion. Conclusions: Amitriptyline, nortriptyline, desipramine, clomipramine, dothiepin, and sertraline were not found in quantifiable amounts in nurslings, and no adverse effects were reported. Therefore, these are the drugs of choice for breast-feeding women. Adverse effects were described in some young infants whose mothers had been treated with doxepin or fluoxetine during breast-feeding. The collective serum level data suggest that infants older than 10 weeks are at low risk for adverse effects of tricyclics, and there is no evidence of accumulation. Research needs include an expanded database of mother-baby serum levels, behavioral assessments of infants during nursing, and longitudinal developmental evaluation of nurslings. Prescription of all antidepressant for a breast-feeding woman is a case-specific risk-benefit decision.

Objective: The authors attempted to reduce the rate of postpartum depression in high-risk women and to increase the time to recurrence. Method: Nondepressed pregnant women with at least one past episode of postpartum major depression were recruited into a randomized clinical trial. Mothers were assigned randomly to a 17-week trial of sertratine or placebo immediately after birth and assessed for 20 sequential weeks with the Hamilton Rating Scale for Depression. Results: Of 14 subjects who took sertraline, one (7%) suffered a recurrence. Of eight subjects who were assigned to placebo, four (50%) suffered recurrences. This difference was significant. The time to recurrence was significantly longer in the sertraline-treated women than in the placebo-treated women. Conclusions: Sertraline conferred preventive efficacy for postpartum-onset major depression beyond that of placebo.

Objective: The authors' goal was to study the serum sertraline levels of breast-feeding mothers and their infants. Method: They obtained serum levels of sertraline and N-desmethylsertraline in nine mother-infant pairs. Results: Sertraline levels were very low (less than 2 ng/ml) in seven of the nine infants and low (3 ng/ml) in one. N-Desmethylsertraline levels were also low (6 ng/ml or less) in seven of the nine infants. One infant had a high level of N-desmethylsertraline, and one infant had unusual serum sertraline and N-desmethylsertraline values (half of its mother's levels). All infants were thriving. Conclusions: Most breast-feeding infants whose mothers were taking sertraline had very low serum levels of both sertraline and N-desmethylsertraline, consistent with published reports. The authors discuss in detail the one infant with unusually high levels.

About 10 to 15 percent of postpartum women suffer from depression. However, there have been few reports in the literature of drugs evaluated for treating postpartum depression. One potential complication is that the infant will be adversely affected by the drug, if the mother is breast feeding her child. Also, the mother may not absorb the drug as she normally would because of the physiological changes in her body due to childbirth and nursing. In the present paper, seven postpartum women suffering from depression were treated with nortriptyline, an antidepressant medication. The healthy infants were aged six months or less. After a minimum of 15 days at a stable dose of the drug, blood samples were taken from mothers within three hours of nursing their infants; blood samples were also taken from the infants at this time. Even though the blood levels in the mothers were clinically effective, no infant had a detectible level of nortriptyline in his blood. This suggests that nortriptyline was not passed to the baby in breast feeding. In the blood of two of the youngest infants, a less active byproduct of nortriptyline, 10-hydroxynortriptyline, was found. However, no adverse effects in any infant were observed. (Consumer Summary produced by Reliance Medical Information, Inc.)

Objective: The Committee on Research on Psychiatric Treatments of the American Psychiatric Association identified treatment of major depression during pregnancy as a priority area for improvement in clinical management. The goal of this article was to assist physicians in optimizing treatment plans for childbearing women. Method: The authors' work group developed a decision-making model designed to structure the information delivered to pregnant women in the context of the risk-benefit discussion. Perspectives of forensic and decision-making experts were incorporated. Results: The model directs the psychiatrist to structure the problem through diagnostic formulation and identification of treatment options for depression. Reproductive toxicity in five domains (intrauterine fetal death, physical malformations, growth impairment, behavioral teratogenicity, and neonatal toxicity) is reviewed for the potential somatic treatments. The illness (depression) also is characterized by symptoms of somatic dysregulation that compromise health during pregnancy. The patient actively participates and provides her evaluation of the acceptability of the various treatments and outcomes. Her capacity to participate in this process provides evidence of competence to consent. Included in the decision-making process are the patient's significant others and obstetrical physician. The process is ongoing, with the need for incorporation of additional data as the pregnancy and treatment response progress. Conclusions: The conceptual model provides structure to a process that is frequently stressful for both patients and psychiatrists. By applying the model, clinicians will ensure that critical aspects of the risk-benefit discussion are included in their care of pregnant women. (Am J Psychiatry 2000; 157:1933-1940)

In a series of eight pregnant women, the authors found that the doses of tricyclic antidepressants required to achieve remission of symptoms and adequate serum levels increased during the second half of pregnancy. During the final trimester, the mean dose required was 1.6 times the mean dose required when the patients were not pregnant.