Marlene P. Freeman

Dr Freeman discusses a recent study by Pacilio et al that characterized real world practices around ketamine treatment and pregnancy testing, consent processes, and contraception use. She emphasizes the need for individual providers to recognize potential pregnancy exposures to treatments in women of reproductive age.

Aripiprazole has become one of the most commonly prescribed psychotropics, making a more comprehensive understanding of its reproductive safety profile a priority. The goal of the current analysis was to determine the risk of major malformations in infants exposed during the first trimester of pregnancy to aripiprazole compared to infants whose mothers had psychiatric diagnoses but did not use an atypical antipsychotic during pregnancy. The National Pregnancy Registry for Atypical Antipsychotics is a prospective pharmacovigilance program in which pregnant women are enrolled and interviewed during pregnancy and the postpartum period. Medical records are assessed to confirm presence or absence of major malformations. Pregnant women ages 18–45 with psychiatric diagnoses are enrolled. As of April 2020, N = 848 women who had delivered infants were eligible for analyses. A total of 158 women with first trimester exposure to aripiprazole were compared to 690 controls. For 163 infants born to women in the exposed group, seven major malformations were confirmed (4.29%), compared to fourteen of the 690 unexposed infants (1.99%). The unadjusted odds ratio for major malformations between aripiprazole-exposed and unexposed infants was 2.21 (95% confidence interval [CI] = (0.88, 5.57) The adjusted odds ratio for major malformations was 1.35 (95% confidence interval [CI] = (0.43, 4.20). After adjustment for confounding variables, the risk of major malformations after first trimester exposure to aripiprazole was not significant compared to controls. While these results are reassuring, they are limited by relatively small numbers of participants. Future analyses with larger numbers are expected to provide more of a complete and precise reproductive safety profile regarding aripiprazole use during pregnancy. Trial registration: clinicaltrials.gov NCT01246765

In this issue of JAMA, the US Preventive Services Task Force (USPSTF) recommends “that clinicians provide or refer pregnant and postpartum persons who are at in

Background: In a preliminary trial, we assessed the efficacy of vortioxetine for major depressive disorder (MDD) during the menopausal transition. Secondary outcomes included hot flashes (HFs), anxiety, and cognitive complaints. Methods: Perimenopausal and early postmenopausal women with MDD (N = 27) received 8 weeks of open-label, flexible-dose treatment with vortioxetine. The Montgomery-Åsberg Depression Rating Scale (MADRS) was the primary outcome measure. Secondary measures included: HF frequency, the Greene Climacteric Scale (GCS), Menopause-Specific Quality of Life Questionnaire (MEN-QOL), Beck Anxiety Inventory (BAI), Cognitive and Physical Functioning Questionnaire (CPFQ), Digit Symbol Substitution Test (DSST), and Cogstate testing. Results: Of the 27 women, 24 (88.8%) were evaluated (≥1 follow-up), and 21 (77.8%) completed the study; 1 discontinued because of adverse effects. The mean MADRS score decreased significantly ( P = .0001) from 31.3 (standard deviation [SD] = 5.5) at pretreatment to 8.1 (SD = 7.8) at posttreatment. The depression response rate (≥50% reduction in MADRS) and remission rate (final MADRS P = .0030, P = .0001, P = .0001, P = .0001, and P = .0133, respectively); Cogstate test scores did not. Frequency and severity of HFs improved significantly ( P = .0291 and P = .0299, respectively). Conclusions: These data support further study of vortioxetine for treating menopausal depression and associated symptoms.

Background: Failed treatment trials are common in major depressive disorder and treatment-resistant depression, and remotely performed multifaceted, centralized structured interviews can potentially enhance signal detection by ensuring that enrolled patients meet eligibility criteria. Methods: We assessed the use of a specific remote structured interview that validated the diagnosis, level of treatment resistance, and depression severity. The objectives were to (1) assess the rate at which patients who were deemed eligible for participation in trials by site investigators were ineligible, (2) assess the reasons for ineligibility, (3) compare rates of ineligibility between academic and nonacademic sites, (4) compare eligibility between US and non-US sites, and (5) report the placebo response rates in trials utilizing this quality assurance approach, comparing its placebo response rates with those reported in the literature. Methods included a pooled analysis of 9 studies that utilized this methodology (SAFER interviews). Results: Overall, 15.33% of patients who had been deemed eligible at research sites were not eligible after the structured interviews. The most common reason was that patients did not meet the study requirements for level of treatment resistance. Pass rates were significantly higher at non-US compared with US sites (94.6% vs 83.3%, respectively; P < 0.001). There was not a significant difference between academic and nonacademic sites (87.8% vs 82.4%; P = 0.08). Placebo response rates were 13.0% to 27.3%, below the 30% to 40% average in antidepressant clinical trials, suggesting a benefit of the quality assurance provided by these interviews. Conclusions: The use of a remotely structured interview by experienced clinical researchers was feasible and possibly contributed to lower-than-average placebo response rates. The difference between US and non-US sites should be the subject of further research.

This study aims to obtain preliminary data on the efficacy of armodafinil for improving menopause-related fatigue and quality of life. Women (aged 40-65 y) experiencing menopause-related fatigue received open-label armodafinil therapy (up to 150 mg/d) for 4 weeks. Changes from baseline in Brief Fatigue Inventory score and Menopause-Specific Quality of Life (MENQOL) physical domain score were examined using the Wilcoxon signed rank test. Exploratory analyses examined the effects of armodafinil on hot flashes, overall quality of life, insomnia, depression, anxiety, and perceived cognitive performance. After open-label treatment, participants were randomized to double-blind continuation of armodafinil versus placebo for 2 weeks to examine whether treatment discontinuation would precipitate symptom recurrence. Of 29 eligible participants, 20 women (69.0%) completed the trial. During treatment with armodafinil (mean dose, 120 mg/d), median Brief Fatigue Inventory scores decreased by 57.7% from 5.2 (interquartile range [IQR], 4.6-6.2) to 2.2 (IQR, 1.1-4.4; P = 0.0002), and median MENQOL physical domain scores decreased by 51.3% from 3.9 (IQR, 2.3-4.8) to 1.9 (IQR, 1.3-2.7; P = 0.0001). Median hot flashes for 24 hours decreased by 48.3% from 2.9 (IQR, 1.1-4.6) to 1.5 (IQR, 0.4-2.4; P = 0.0005). Improvements in MENQOL total score (49%; P = 0.0001), cognitive function (59.2%; P = 0.0002), depressive symptoms (64.7%; P = 0.0006), insomnia (72.7%; P = 0.0012), and excessive sleepiness (57.1%; P = 0.0006) were noted. Randomized continuation (n = 10) or discontinuation (n = 10) did not indicate group differences. Armodafinil was well-tolerated; three women (12%) were withdrawn for adverse events. These preliminary results suggest a therapeutic effect of armodafinil on fatigue affecting quality of life during menopause, and a potential benefit for other menopause-related symptoms.