Mental Health in Obstetric Patients and Providers During the COVID-19 Pandemic.

Psychiatric morbidity is the most common childbirth complication with 1 in 5 women experiencing a perinatal mood or anxiety disorder. The cost of this psychiatric morbidity is pervasive, contributing to devastating maternal health, child developmental, and economic consequences. The coronavirus disease 2019 (COVID-19) pandemic, and associated changes to perinatal experiences, resulted in profound psychological reactions including increased anxiety, depression, stress disorders, and sleep disturbance, further impacting obstetric patients. Providers' mental health has been challenged by moral injury and shared trauma. This article reviews mental health outcomes in regard to the COVID-19 pandemic for obstetric patients and their providers.

Donepezil Treatment in Patients With Depression and Cognitive Impairment on Stable Antidepressant Treatment: A Randomized Controlled Trial.

OBJECTIVE: Depression and cognitive impairment are often comorbid in older adults, but optimal treatment strategies remain unclear. In a two-site study, the efficacy and safety of add-on donepezil versus placebo were compared in depressed patients with cognitive impairment receiving stable antidepressant treatment. METHODS: A randomized, double-blind, placebo-controlled trial was conducted in older adults with depression and cognitive impairment (https://clinicaltrials.gov/ct2/show/NCT01658228; NCT01658228). Patients received open-label antidepressant treatment for 16 weeks, initially with citalopram and then with venlafaxine, if needed, followed by random assignment to add-on donepezil 5-10 mg daily or placebo for another 62 weeks. Outcome measures were neuropsychological test performance (Alzheimer's Disease Assessment Scale-Cognitive subscale [ADAS-Cog] and Selective Reminding Test [SRT] total immediate recall) and instrumental activities of daily living (Functional Activities Questionnaire). RESULTS: Of 81 patients who signed informed consent, 79 patients completed the baseline evaluation. Open antidepressant treatment was associated with improvement in depression in 63.93% responders by week 16. In the randomized trial, there were no treatment group differences between donepezil and placebo on dementia conversion rates, ADAS-Cog, SRT total immediate recall, or FAQ. Neither baseline cognitive impairment severity nor apolipoprotein E e4 genotype influenced donepezil efficacy. Donepezil was associated with more adverse effects than placebo. CONCLUSION: The results do not support adjunctive off-label cholinesterase inhibitor treatment in patients with depression and cognitive impairment. The findings highlight the need to prioritize discovery of novel treatments for this highly prevalent population with comorbid illnesses.

Clinical and radiological characteristics of early versus late mild cognitive impairment in patients with comorbid depressive disorder.

OBJECTIVE: The classification of mild cognitive impairment (MCI) continues to be debated though it has recently been subtyped into late (LMCI) versus early (EMCI) stages. Older adults presenting with both a depressive disorder (DEP) and cognitive impairment (CI) represent a unique, understudied population. Our aim was to examine baseline characteristics of DEP-CI patients in the DOTCODE trial, a randomized controlled trial of open antidepressant treatment for 16 weeks followed by add-on donepezil or placebo for 62 weeks. METHODS/DESIGN: Key inclusion criteria were diagnosis of major depression or dysthymic disorder with Hamilton Depression Rating Scale (HAM-D) score >14, and cognitive impairment defined by MMSE score ≥21 and impaired performance on the WMS-R Logical Memory II test. Patients were classified as EMCI or LMCI based on the 1.5 SD cutoff on tests of verbal memory, and compared on baseline clinical, neuropsychological, and anatomical characteristics. RESULTS: Seventy-nine DEP-CI patients were recruited of whom 39 met criteria for EMCI and 40 for LMCI. The mean age was 68.9, and mean HAM-D was 23.0. Late mild cognitive impairment patients had significantly worse ADAS-Cog (P < .001), MMSE (P = .004), Block Design (P = .024), Visual Rep II (P = .006), CFL Animal (P = .006), UPSIT (P = .051), as well as smaller right hippocampal volume (P = .037) compared to EMCI patients. MRI indices of cerebrovascular disease did not differ between EMCI and LMCI patients. CONCLUSIONS: Cognitive and neuronal loss markers differed between EMCI and LMCI among patients with DEP-CI, with LMCI being more likely to have the clinical and neuronal loss markers known to be associated with Alzheimer's disease.

Combined treatment with memantine/es-citalopram for older depressed patients with cognitive impairment: a pilot study.

OBJECTIVE: The objective of the study is to assess combined antidepressant and memantine treatment in older patients presenting with depression and cognitive impairment. METHODS: Thirty-five depressed patients with cognitive impairment participated in this open-label pilot study. We evaluated whether, over a 48-week period, combined antidepressant (primarily es-citalopram) and memantine treatment was effective in the treatment of cognitive impairment and depression. Neuropsychological testing was performed, and antidepressant response monitored at baseline and at the 12, 24, and 48-week time points. RESULTS: Treatment with escitalopram (mean daily dose 18.62 mg, SD 5.15) and memantine (mean daily dose 13.62 mg, SD 6.67) was associated with improvement in Hamilton Depression Rating Scale scores over the 48-week study period. Patients demonstrated significant improvement in the primary outcome of cognitive performance (Selective Reminding Test total immediate recall; SRT-IR) over the 48-week treatment period (p = 0.0147). Significant improvement was also observed in measures of naming and verbal fluency but not in the other cognitive domains. One of the 35 patients (2.9%) converted to Alzheimer's disease over the 48-week treatment period. In the amnestic mild cognitive impairment subsample (n = 22), the conversion rate was 4.5%, a rate lower than in other reports of patients with DEP-CI. CONCLUSIONS: In this open-label trial, combined antidepressant and memantine treatment in patients with DEP-CI was associated with improved cognition and a low rate of conversion to dementia compared with published studies in patients with DEP-CI. Although limited by the open-label study design that incorporates practice effects that can improve cognitive test performance, the findings suggest the need for a larger randomized placebo-controlled trial.

Addressing mental health in patients and providers during the COVID-19 pandemic.

The pandemic, and the associated changes to pregnancy and postpartum experiences, can lead to profound psychological reactions including panic, hyperarousal, sleep disturbance, anxiety, depression, and traumatic stress disorders. Providers face compassion fatigue and shared trauma. In this article, we describe the mental health outcomes known to date in regard to the novel coronavirus disease 2019 pandemic for obstetric patients and their providers as well as therapeutic approaches, including our novel embedded mental health service, to address these mental health needs.

An open treatment trial of duloxetine in elderly patients with dysthymic disorder.

OBJECTIVE: We evaluated the efficacy and side effects of the selective serotonin and norepinephrine reuptake inhibitor antidepressant duloxetine in older adults with dysthymic disorder. METHODS: Patients ≥ 60 years old with dysthymic disorder received flexible dose duloxetine 20-120 mg daily in an open-label 12-week trial. The main outcomes were change from baseline to 12 weeks in 24-item Hamilton Depression Rating Scale scores and Treatment Emergent Symptoms Scale scores. Response required ≥ 50% decline in Hamilton Depression Rating Scale scores with a Clinical Global Impression of much improved or better, and remission required final Hamilton Depression Rating Scale ≤ 6. Intent-to-treat analyses were conducted with the last observation carried forward. RESULTS: In 30 patients, the mean age was 70.7 (standard deviation (SD) = 7.6) years and 56.7% were female. In intent-to-treat analyses, there were 16 responders (53.3%) and 10 remitters (33.3%). Of these, 19 patients completed the trial. The mean maximum dose was 76.3 mg (SD = 38.5) in the total sample and 101 mg (SD = 17.9) in completers. In the total sample, the mean final dose was 51 mg (SD = 27.2) and correlated significantly with decline in Hamilton Depression Rating Scale (p < .03); decline in Hamilton Depression Rating Scale correlated significantly with decline in Treatment Emergent Symptoms Scale (p < .001). Daily doses above 60 mg were associated with greater improvement and well tolerated. This result was partly confounded by early dropouts having received low doses. Demographic and medical comorbidities, including cardiac disease and hypertension, were not related to response. Somatic side effects were common prior to duloxetine treatment and improved rather than worsened with duloxetine. There were no serious adverse events. CONCLUSION: Duloxetine at relatively high doses showed moderate efficacy in elderly patients with dysthymic disorder and was well tolerated in successful completers. Reduced somatic symptoms were associated with improvement in depressive symptoms. A systematic placebo-controlled trial of duloxetine in older patients with dysthymic disorder may be warranted.

Donepezil treatment of older adults with cognitive impairment and depression (DOTCODE study): clinical rationale and design.

Treatment strategies for patients with depression and cognitive impairment (DEP-CI), who are at high risk to develop a clinical diagnosis of dementia, are not established. This issue is addressed in the donepezil treatment of cognitive impairment and depression (DOTCODE) pilot clinical trial. The DOTCODE study is the first long-term treatment trial that assesses differences in conversion to dementia and cognitive change in DEP-CI patients using a study design of open antidepressant medication plus add-on randomized, double-blind, placebo-controlled treatment with the acetylcholinesterase inhibitor donepezil. In Phase 1, DEP-CI patients receive optimized antidepressant treatment for 16 weeks. In Phase 2, antidepressant treatment is continued with the addition of randomized, double-blind treatment with donepezil or placebo. The total study duration for each patient is 78 weeks (18 months). Eighty DEP-CI outpatients (age 55 to 95 years) are recruited: 40 at New York State Psychiatric Institute/Columbia University and 40 at Duke University Medical Center. The primary outcome is conversion to a clinical diagnosis of dementia. The secondary outcomes are cognitive change scores in Selective Reminding Test (SRT) total recall and the modified Alzheimer's Disease Assessment Scale (ADAS-cog). Other key assessments include the 24-item Hamilton Depression Rating Scale and antidepressant response; Clinical Global Impression (CGI) for depression, cognition, and global status; neuropsychological test battery for diagnosis; informant report of functional abilities (Pfeffer FAQ); and Treatment Emergent Symptom Scale (TESS) for somatic side effects. Apolipoprotein E ε4 status, odor identification deficits, and MRI entorhinal/hippocampal cortex atrophy at baseline are evaluated as neurobiological moderators of donepezil treatment effects.