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Postpartum Depression Treatment In 19th Century

In a study of 87 women with major or minor depression in the postpartum period, subjects were randomized to one of four groups receiving either fluoxetine or placebo plus one or six cognitive behavioral therapy (CBT) based counseling sessions.52 Breastfeeding mothers were excluded from the study. Improvement was seen in all groups, with greater reduction in depression severity in the fluoxetine group compared to the placebo medication, and greater improvement with six counseling sessions compared to one session. Women receiving both fluoxetine and counseling did not differ significantly in outcome compared to women who received fluoxetine alone. Because the mean baseline level of depressive symptoms based on rating scales was mild, the findings are not easily generalized to a population with more severe postpartum depression.

postpartum depression treatment in 19th century

A subsequent study randomized 35 women with postpartum depression and comorbid anxiety to receive paroxetine or paroxetine plus CBT for 12 weeks.53 Both groups showed significant improvement in depressive and anxiety symptoms (response rates 87.5% in the paroxetine group and 78.9% in the combined group) without significant differences between groups. The study did not include a placebo arm, making analysis of the specific effects of either intervention difficult. A third study compared paroxetine to placebo in an 8-week randomized controlled trial.54 The attrition rate in this study was high, with only 31 of 70 participants completing the study (17 in the paroxetine arm and 14 in the placebo arm), but the authors found lower mean severity scores and a higher remission rate after 8 weeks of treatment with paroxetine compared to placebo.

Very few studies have compared different classes of medications used in postpartum depression. One comparative study found treatment with nortriptyline to yield similar outcomes as treatment with sertraline.55 After 8 weeks of treatment in this large, randomized, double-blind trial, both groups showed improvement, and response rates (nortriptyline 69%, sertraline 56%), remission rates (nortriptyline 48%, sertraline 46%) and side effect burden were similar between groups at week 4, 8 and 24, though side effect profiles differed. There was no placebo arm. The response rate could be predicted earlier in the group receiving sertraline, but the overall response rates were equivalent. Sub-analyses of this study revealed an improvement in maternal role function56 and sexual function57 that was equivalent in both groups.

In a double-blind placebo-controlled study by Gregoire et al 61 women with postpartum depression were randomized to receive estrogen or placebo patches.88 Breastfeeding women were excluded. Over the first month of treatment, women receiving estrogen showed greater and more rapid improvement in their symptoms as measured on the Edinburgh Postnatal Depression Scale and in clinical interviews. Women in the placebo group also improved, but maintained depression scores above the screening threshold. Neither group had complete remission of symptoms. The authors did not control for women receiving concomitant antidepressant medication, which was more common in the estrogen treatment group, making interpretation of the study results difficult. Additionally, women were included in the study up to 18 months postpartum, by which time the effects the postpartum drop in estrogen would likely have resolved.86

Although an early naturalistic study suggested progesterone as a promising preventative therapy against recurrent postpartum depression,89,90 the results of that study were contradicted by a subsequent double-blind, placebo-controlled trial that found an increase in depressive symptoms in women treated with norethisterone enanthate, a synthetic progestogen.91 In this study, 180 women were randomized to receive one depot injection of norethisterone enanthate or one injection of saline placebo within 48 hours after delivery and were followed for three months. The investigators found that women who received the synthetic progestogen were more likely to develop depressive symptoms, more likely to have bleeding, and more likely to complain of exhaustion. A recent review of the above studies concluded that while the research on estrogen is promising but preliminary, there is no role for synthetic progestogens in the treatment of PPD, and that given the increased risk for depressive symptoms their use as contraception in this population is questionable.92

Other studies without control groups support an effect of estrogen in the treatment of postpartum depression. A small prevention study found that when a slow taper of estrogen therapy was administered immediately after birth to 11 women with a history of postpartum psychosis or depression only one woman suffered a relapse episode.93 Another small study treated 23 women with severe postpartum depression with sublingual 17-beta estradiol over 8 weeks, and found remission of symptoms in 19 of the women, which the authors correlated with increased serum estrogen levels in the subjects.94 Both studies should be interpreted with caution, given the lack of a comparison group.

Despite these epidemiologic associations, studies examining the use of omega-3 fatty acids for treatment of perinatal depression have had mixed results. Freeman et al conducted two pilot studies of omega-3 fatty acids as an intervention for perinatal depression; one was an open-label flexible-dose trial of a combination of EPA and DHA for the treatment of MDD during pregnancy,133 and the second trial assessed the efficacy of omega-3 fatty acids for postpartum depression in an 8-week randomized dose-ranging study.134 The outcome of the first trial showed a 40.9% mean decrease in depressive symptoms on the Edinburgh Postnatal Depression Scale. The second study, a randomized dose-ranging trial for postpartum depression found no significant difference between control and study group. Both studies were limited by their small sample sizes (n = 15 and 16, respectively) and their lack of a placebo group. A subsequent randomized placebo-controlled study investigating the combination of omega-3 fatty acids and supportive psychotherapy for the treatment of perinatal depression135 again demonstrated no significant difference between the omega-3 fatty acids and placebo, though participants in both groups experienced significant decreases in their depression rating scales. The benefits of supportive psychotherapy received by both groups may have limited the ability to detect a specific effect of omega-3 fatty acids. A subsequent small, randomized, double blind, placebo-controlled trial investigating omega-3 fatty acids at a dose of 3.4 g per day as monotherapy for major depression during pregnancy136 demonstrated a benefit from this intervention. Although there was relatively high attrition in both groups, subjects receiving omega-3 fatty acids had significantly lower scores on depression rating scales as compared to the placebo group at the study end point.

Psychopharmacologic treatment of PPD is complicated by both known and unknown risks of medication in breast milk. There have been few medication trials specifically evaluating the effectiveness of antidepressant medication or ECT for postpartum depression, but the available evidence suggests that medications typically used to treat major depression in the general population are equally effective in postpartum depression. All medications pass into breast milk, though the extent of passage varies considerably between drugs, and sertraline, paroxetine and nortriptyline currently appear to have the best safety profiles in breastfeeding. There have been case reports of adverse effects in nursing infants of antidepressant medication in breast milk, but the advantages of breastfeeding to the mother and infant may outweigh the risks of exposure. Exposed infants should be monitored for any acute behavioral changes. However, the long-term risks of medication exposure to the infant remain unknown. Most experts recommend that the choice of medication in the postpartum should be based first on known efficacy for an individual woman, and that known milk-plasma ratios should be a secondary consideration unless a patient is treatment-naïve. Some studies suggest that estrogen may be an effective agent for treatment, prevention or augmentation in depressed postpartum women; however data remains limited and there are significant health considerations with hormonal intervention.

There is evidence in explaining these relationships suggesting that women with a positive history of depression are more susceptible to hormonal changes.[18] In support of this finding, it has reported that a history of moderate to severe premenstrual syndrome (PMS) is a factors affecting the onset of postpartum depression.[19] In women with severe PMS, the serotonin transport system will change while the serotonin transporter polymorphism area is associated with major depression.[20] High serotonin polymorphism may lead to tryptophan depletion and induction of postpartum major depression.[21]

Risky pregnancy is also associated with an increased risk of postpartum depression. These risks include conditions that lead to performing emergency cesarean section or hospitalization during pregnancy. Postpartum complications[22,24] are also effective on the incidence of postpartum depression as much as during labor complications such as meconium passage, umbilical cord prolapse, and obstetric hemorrhages.[10] Mothers with the birth of an infant with a weight

A mismatch between the expectations of mother and pregnancy events is as factors that affect the occurrence of depression. It has been reported that women with strong desire to have natural childbirth during the perinatal period whose delivery are done by caesarean section are more prone to risk for postpartum depression than others.[26] Spending the course of pregnancy in a natural state away from the excitements due to complications during pregnancy and preparedness for the delivery seem to be as conditions effective in the prevention of postpartum depression. Since it has been reported that the use of epidural anesthesia during childbirth, attending in childbirth preparation classes during pregnancy, and continued breastfeeding after childbirth were associated with a reduced risk of postpartum depression.[27] However, insomnia during pregnancy can lead to the risk of recurrent postpartum depression in women with a previous history of the disease.[28]


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