Katherine L. Wisner

Major Depression and Antidepressant Treatment: Impact on Pregnancy and Neonatal Outcomes

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%.

Nutrition and Depression: Implications for Improving Mental Health Among Childbearing-Aged Women

Adequate nutrition is needed for countless aspects of brain functioning. Poor diet quality, ubiquitous in the United States, may be a modifiable risk factor for depression. The objective was to review and synthesize the current knowledge of the role of nutrition in depression, and address implications for childbearing-aged women. Poor omega-3 fatty acid status increases the risk of depression. Fish oil and folic acid supplements each have been used to treat depression successfully. Folate deficiency reduces the response to antidepressants. Deficiencies of folate, vitamin B12, iron, zinc, and selenium tend to be more common among depressed than nondepressed persons. Dietary antioxidants have not been studied rigorously in relation to depression. Childbearing-aged women are particularly vulnerable to the adverse effects of poor nutrition on mood because pregnancy and lactation are major nutritional stressors to the body. The depletion of nutrient reserves throughout pregnancy and a lack of recovery postpartum may increase a womans risk of depression. Prospective research studies are needed to clarify the role of nutrition in the pathophysiology of depression among childbearing-aged women. Greater attention to nutritional factors in mental health is warranted given that nutrition interventions can be inexpensive, safe, easy to administer, and generally acceptable to patients.

Diminished response to pleasant stimuli by depressed women

This study examined the self-report and facial expressions of emotional response to pictorial stimuli and the incidental learning of pleasant and unpleasant words by depressed (n = 20) and nondepressed (n = 20) women. Depression was associated with reports of diminished emotional response and reduced frequency and intensity of facial expressions only to pleasant stimuli. The 2 groups did not differ in response to hedonically unpleasant stimuli, even those specifically relevant to the emotion of sadness. In a similar vein, depressed and nondepressed participants showed differences in incidental recall for only pleasant self-referential terms. There was no difference in recall of unpleasant words. These findings suggest the importance of hedonic deficits on psychological processes in clinical depression.

The management of depression during pregnancy: a report from the American Psychiatric Association and the American College of Obstetricians and Gynecologists

OBJECTIVE To address the maternal and neonatal risks of both depression and antidepressant exposure and develop algorithms for periconceptional and antenatal management. METHOD Representatives from the American Psychiatric Association, the American College of Obstetricians and Gynecologists and a consulting developmental pediatrician collaborated to review English language articles on fetal and neonatal outcomes associated with depression and antidepressant treatment during childbearing. Articles were obtained from Medline searches and bibliographies. Search keywords included pregnancy, pregnancy complications, pregnancy outcomes, depressive disorder, depressive disorder/dt, abnormalities/drug-induced/epidemiology, abnormalities/drug-induced/et. Iterative draft manuscripts were reviewed until consensus was achieved. RESULTS Both depressive symptoms and antidepressant exposure are associated with fetal growth changes and shorter gestations, but the majority of studies that evaluated antidepressant risks were unable to control for the possible effects of a depressive disorder. Short-term neonatal irritability and neurobehavioral changes are also linked with maternal depression and antidepressant treatment. Several studies report fetal malformations in association with first trimester antidepressant exposure but there is no specific pattern of defects for individual medications or class of agents. The association between paroxetine and cardiac defects is more often found in studies that included all malformations rather than clinically significant malformations. Late gestational use of selective serotonin reuptake inhibitor antidepressants is associated with transitory neonatal signs and a low risk for persistent pulmonary hypertension in the newborn. Psychotherapy alone is an appropriate treatment for some pregnant women; however, others prefer pharmacotherapy or may require pharmacological treatment. CONCLUSIONS Antidepressant use in pregnancy is well studied, but available research has not yet adequately controlled for other factors that may influence birth outcomes including maternal illness or problematic health behaviors that can adversely affect pregnancy.

Randomized dose-ranging pilot trial of omega-3 fatty acids for postpartum depression

Objective:  Postpartum depression (PPD) affects 10–15% of mothers. Omega‐3 fatty acids are an intriguing potential treatment for PPD.

Perinatal mental illness: Definition, description and aetiology

Perinatal mental illness is a significant complication of pregnancy and the postpartum period. These disorders include depression, anxiety disorders, and postpartum psychosis, which usually manifests as bipolar disorder. Perinatal depression and anxiety are common, with prevalence rates for major and minor depression up to almost 20% during pregnancy and the first 3 months postpartum. Postpartum blues are a common but lesser manifestation of postpartum affective disturbance. Perinatal psychiatric disorders impair a womans function and are associated with suboptimal development of her offspring. Risk factors include past history of depression, anxiety, or bipolar disorder, as well psychosocial factors, such as ongoing conflict with the partner, poor social support, and ongoing stressful life events. Early symptoms of depression, anxiety, and mania can be detected through screening in pregnancy and the postpartum period. Early detection and effective management of perinatal psychiatric disorders are critical for the welfare of women and their offspring.

Omega-3 fatty acids and supportive psychotherapy for perinatal depression: A randomized placebo-controlled study

BACKGROUND Perinatal major depressive disorder (MDD), including antenatal and postpartum depression, is common and has serious consequences. This study was designed to investigate the feasibility, safety, and efficacy of omega-3 fatty acids for perinatal depression in addition to supportive psychotherapy. METHODS Perinatal women with MDD were randomized to eicosapentaenoic (EPA) and docosahexaenoic acids (DHA), 1.9g/day, or placebo for 8weeks. A manualized supportive psychotherapy was provided to all subjects. Symptoms were assessed with the Hamilton Rating Scale for Depression (HAM-D) and Edinburgh Postnatal Depression Scale (EPDS) biweekly. RESULTS Fifty-nine women enrolled; N = 51 had two data collection points that allowed for evaluation of efficacy. Omega-3 fatty acids were well tolerated. Participants in both groups experienced significant decreases in EPDS and HAM-D scores (p<.0001) from baseline. We did not find a benefit of omega-3 fatty acids over placebo. Dietary omega-3 fatty acid intake was low among participants. LIMITATIONS The ability to detect an effect of omega-3 fatty acids may have been limited by sample size, study length, or dose. The benefits of supportive psychotherapy may have limited the ability to detect an effect of omega-3 fatty acids. CONCLUSIONS There was no significant difference between omega-3 fatty acids and placebo in this study in which all participants received supportive psychotherapy. The manualized supportive psychotherapy warrants further study. The low intake of dietary omega-3 fatty acids among participants is of concern, in consideration of the widely established health advantages in utero and in infants.

Postpartum depression: a randomized trial of sertraline versus nortriptyline.

Abstract: Symptom reduction and improvement in functioning in women with postpartum major depression treated with a tricyclic antidepressant versus a serotonin reuptake inhibitor were compared. The design was a double-blind, 8-week comparative trial of nortriptyline (NTP) versus sertraline (SERT) with a 16-week continuation phase. Women aged 18 to 45 years with postpartum major depression and a 17-item Hamilton Rating Scale for Depression score of 18 or more were eligible. Subjects were randomized to NTP or SERT and treated with a fixed-dosing strategy. Of 420 women interviewed, 109 eligible women received medication, and 95 provided follow-up data. The proportion of women who responded and remitted did not differ between drugs at 4, 8, or 24 weeks. Times to response and remission also did not differ. Psychosocial functioning improved similarly in both drug-treated groups of mothers. The total side effect burden of each drug was similar, although side effect profiles differed between agents. No clinical or demographic variables differentiated responders by drug. Women who were responders and remitters at week 8 could be identified earlier if they were treated with SERT than with NTP. Breast-fed infant serum levels were near or below the level of quantifiability for both agents.

Gonadal steroids in the treatment of mood disorders

UNLABELLED Increased interest in the complex interplay between gonadal steroids and neurotransmitter systems involved in mood has led investigators to question the role of gonadal steroids in the treatment of affective disorders, especially in women. OBJECTIVES The purpose of this article is to provide a rationale for using gonadal hormones in the treatment of depression in women. METHODS The literature is reviewed regarding 1) sex-specific phenomenologic and epidemiologic differences in the manifestation of psychiatric illness, 2) sex-specific differences in the therapeutic and adverse effects of psychotropic medications, 3) the complex interplay between gonadal steroids and neurotransmitter systems implicated in psychiatric disorders, and 4) the growing literature regarding the use of estrogen and progesterone in the treatment of mood disorders in women and androgens in the treatment of depression and sexual dysfunction in both men and women. RESULTS Findings from pharmacologic trials of estrogen and androgens are encouraging, albeit mixed, in the treatment of mood disorders and decreased libido in women, respectively. Controlled studies have failed to confirm early open-label reports of the effectiveness of progesterone in the treatment of premenstrual syndrome. CONCLUSIONS Pending replication, estrogen may become an important pharmacologic agent in the treatment of postnatal and perimenopausal depression, whereas androgens have been shown to improve libido in postmenopausal women and hypogonadal men. Progesterone cannot be recommended as a treatment for premenstrual syndrome or postnatal depression.

Screening for Depression in the Postpartum Period: A Comparison of Three Instruments

OBJECTIVES Postpartum depression, the most prevalent complication of childbirth, is often unrecognized. Our objective was to compare the effectiveness of three screening instruments--Edinburgh Postnatal Depression Scale (EPDS), Patient Health Questionnaire (PHQ-9), and the 7-item screen of the Postpartum Depression Screening Scale (PDSS)--for identifying women with postpartum depression in the first 6 months after delivery. METHODS We administered the three instruments via telephone to women who were > or =18 years and had delivered infants 6-8 weeks earlier. We arranged home interviews to confirm DSM-IV criteria current major depressive disorder (MDD) in women who had an above-threshold score on any of the instruments. For women who screened negative on the 6-8 week call, we repeated the screening at 3 months and 6 months to identify emergent symptoms. The primary outcome measures were the screening scores and DSM-IV diagnoses. RESULTS Of 135 women reached, 123 (91%) were screened, 29 (24%) had home visits, and 13 (11%) had an MDD within 6 months of delivery. Analyses of the scores at 6-8 weeks postpartum and the DSM-IV diagnoses indicated the EPDS at a cutoff point of > or =10 identified 8 (62%) of cases, the PHQ-9 at a cutoff point of > or =10 identified 4 (31%), and the PDSS 7-item Short Form (PDSS_SF) at a cutoff point of > or =14 identified 12 (92%). However, 15 of 16 (94%) women without current MDD screened positive on the PDSS_SF. The EPDS was significantly more accurate (p = 0.01) than the PDSS_SF and PHQ-9 with the cutoff points used. After correcting for verification bias, we found the EPDS and the PDSS_SF were significantly more accurate than the PHQ-9 (p < 0.03). CONCLUSIONS Administering the EPDS by phone at 6-8 weeks postpartum is an efficient and accurate way to identify women at high risk for postpartum depression within the first 6 months after delivery.