Lee S. Cohen

Background: Second-generation antipsychotics (SGAs), also called atypical antipsychotics, are common therapies for women with a spectrum of psychiatric disorders. No systematically ascertained human reproductive safety data are available for lurasidone, and prospective data for quetiapine are limited, making decisions regarding use of these medications during pregnancy complicated. Materials and Methods: The National Pregnancy Registry for Psychiatric Medications is a prospective cohort study designed to collect reproductive safety data relative to SGAs. Pregnant women aged 18–45 years, with psychiatric illness and prenatal psychotropic medication exposure completed three phone interviews during pregnancy and the postpartum period. Cases of presumed malformations are abstracted from medical records for adjudication by a teratologist blinded to medication exposure. Results: Of 2,293 women enrolled at the time of analysis, 134 in the lurasidone group, 264 in the quetiapine group, and 886 controls completed the postpartum interview and were therefore eligible for inclusion. Dropped or lost-to-follow-up participants (13%) and those currently pregnant were excluded. Participants were predominantly White, college-educated, and married (lurasidone = 88.1%, 76.9%, 77.6%; quetiapine = 89.8%, 71.2%, 75.0%; controls = 92.7%, 86.7%, 89.1%). Absolute risks of major malformations were 2.19% (lurasidone), 1.85% (quetiapine), and 1.77% (controls). Odds ratios comparing lurasidone and quetiapine with controls were 1.24 (95% confidence interval [CI] = 0.36–4.32) and 1.04 (95% CI = 0.38–2.85), respectively. Conclusions: No specific patterns of malformations were observed in infants exposed to the medications of interest. Lurasidone and quetiapine did not appear to be major teratogens, but further information is needed to refine risk estimates. Food and Drug Administration guidance underscores the importance of pregnancy registries. Clinical trial number: NCT01246765.

Objective This study aims to determine the efficacy and tolerability of omega-3 fatty acids in reducing vasomotor symptoms (VMS) frequency and bother in perimenopausal and postmenopausal women. Methods This study was a 12-week, three-by-two factorial, randomized controlled trial. Eligible women were randomized to a double-blind comparison of omega-3 (n = 177) or placebo (n = 178) capsules, and simultaneously to yoga (n = 107), aerobic exercise (n = 106), or their usual physical activity (n = 142). Participants received 1.8 g of omega-3 daily for 12 weeks. Each capsule contained ethyl eicosapentaenoic acid (425 mg), docosahexaenoic acid (100 mg), and other omega-3s (90 mg). Primary outcomes were VMS frequency and bother. Secondary outcomes included sleep quality (Pittsburgh Sleep Quality Index), insomnia symptoms (Insomnia Severity Index), depressive symptoms (Physician’s Health Questionnaire-8), and anxiety (Generalized Anxiety Disorder-7). Results The mean baseline frequency of VMS per day was 7.6 (95% CI, 7.0 to 8.2). After 12 weeks, the reduction in VMS frequency with omega-3 (−2.5; 95% CI, −3.0 to −1.9) did not differ significantly from that with placebo (−2.7; 95% CI, −3.3 to −2.2), with a relative difference of 0.3 fewer hot flashes per day (95% CI, −0.5 to 1.0; P = 0.28). Changes in VMS bother at 12 weeks were also similar between groups, with no relative difference on a four-point scale (95% CI, −0.1 to 0.2; P = 0.36). Omega-3s compared with placebo showed no improvement in self-reported sleep or mood (P > 0.09 for all comparisons). Conclusions Among healthy, sedentary perimenopausal and postmenopausal women, a 12-week treatment with omega-3 does not improve VMS frequency, VMS bother, sleep, or mood compared with placebo.

Approximately 6% to 8% of postpartum women suffer from major depressive disorder (MDD), but only a few controlled trials have investigated the efficacy of pharmacologic treatments. The current study determined the relative efficacy of paroxetine compared to placebo in the treatment of acute postpartum MDD. This was an 8-week, multicenter, parallel, placebo-controlled trial of paroxetine for treatment of postpartum depression. Subjects were eligible if they had an onset of DSM-IV MDD after, but within 3 months of, delivery and had a minimum score of 16 on the 17-item Hamilton Rating Scale for Depression (HAM-D-17) at intake. Seventy women were randomly assigned to either immediate-release paroxetine or matching placebo, and 31 completed the trial. Subjects were reassessed with the HAM-D-17, the Inventory of Depressive Symptomatology-Self-Report (IDS-SR) form and the Clinical Global Impressions (CGI) scales. The study was conducted between 1997 and 2004. Both groups improved over time and did not differ significantly on the HAM-D-17 or IDS-SR at follow-up. However, greater improvement in overall mean +/- SD clinical severity was found for the paroxetine (Clinical Global Impressions-Severity of Illness [CGI-S] score = 1.8 +/- 1.4) compared with the control group (CGI-S score = 3.1 +/- 1.4; p = .05). The paroxetine group also had a significantly higher rate of remission, compared to the placebo group (37% vs. 15%, odds ratio = 3.5, 95% CI = 1.1 to 11.5). The rate of adverse effects did not differ significantly between groups. Study results were limited by lower than expected enrollment and higher than anticipated attrition. Nonetheless, paroxetine treatment was associated with a significantly higher rate of remission among women with postpartum onset of MDD.

Transition to menopause has long been considered a period of increased risk for depressive symptoms. However, the extent to which this period is one of increased risk for major depressive disorder is less clear. Some^1,2 but not all,^3,4 studies suggest an association between the menopausal transition and significant psychosocial impairment with concomitant vulnerability to depressive symptoms. These inconsistent findings may be due at least in part to variability in study designs and other methodological limitations. For example, there has been little uniformity with respect to selection of study participants, with some studies targeting specialized menopause clinics, while others have included subjects from community-based samples. Another source of inconsistency across some studies has been the definition of menopausal status. Menopausal status has frequently been assigned based on 1 single criterion (eg, age) or by a combination of various criteria including age, presence of menopause-related symptoms, hormone levels, or history of menstrual cycle irregularity. Last, some studies have lacked a standardized assessment of psychiatric symptoms or disorders and/or rigorous criteria to delineate severity of depressive episodes.^5-7

Research from JAMA — Relapse of Major Depression During Pregnancy in Women Who Maintain or Discontinue Antidepressant Treatment — ContextPregnancy has historically been described as a time of emotional well-being, providing “protection” against psychiatric disorder. However, systematic delineation of risk of relapse in women who maintain or discontinue pharmacological treatment during pregnancy is necessary.ObjectiveTo describe risk of relapse in pregnant women who discontinued antidepressant medication proximate to conception compared with those who maintained treatment with these medications.Design, Setting, and PatientsA prospective naturalistic investigation using longitudinal psychiatric assessments on a monthly basis across pregnancy; a survival analysis was conducted to determine time to relapse of depression during pregnancy. A total of 201 pregnant women were enrolled between March 1999 and April 2003 from 3 centers with specific expertise in the treatment of psychiatric illness during pregnancy. The cohort of women was recruited from (1) within the hospital clinics, (2) self-referral via advertisements and community outreach detailing the study, and (3) direct referrals from the community. Participants were considered eligible if they (1) had a history of major depression prior to pregnancy, (2) were less than 16 weeks' gestation, (3) were euthymic for at least 3 months prior to their last menstrual period, and (4) were currently or recently (<12 weeks prior to last menstrual period) receiving antidepressant treatment. Of the 201 participants, 13 miscarried, 5 electively terminated their pregnancy, 12 were lost to follow-up prior to completion of pregnancy, and 8 chose to discontinue participation in the study.Main Outcome MeasureRelapse of major depression defined as fulfilling Structured Clinical Interview for DSM-IV [Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition] Diagnosis (SCID) criteria.ResultsAmong the 201 women in the sample, 86 (43%) experienced a relapse of major depression during pregnancy. Among the 82 women who maintained their medication throughout their pregnancy, 21 (26%) relapsed compared with 44 (68%) of the 65 women who discontinued medication. Women who discontinued medication relapsed significantly more frequently over the course of their pregnancy compared with women who maintained their medication (hazard ratio, 5.0; 95% confidence interval, 2.8-9.1; P<.001).ConclusionsPregnancy is not “protective” with respect to risk of relapse of major depression. Women with histories of depression who are euthymic in the context of ongoing antidepressant therapy should be aware of the association of depressive relapse during pregnancy with antidepressant discontinuation.