Perioperative mental health intervention for depression and anxiety symptoms in older adults study protocol: design and methods for three linked randomised controlled trials.

INTRODUCTION: Preoperative anxiety and depression symptoms among older surgical patients are associated with poor postoperative outcomes, yet evidence-based interventions for anxiety and depression have not been applied within this setting. We present a protocol for randomised controlled trials (RCTs) in three surgical cohorts: cardiac, oncological and orthopaedic, investigating whether a perioperative mental health intervention, with psychological and pharmacological components, reduces perioperative symptoms of depression and anxiety in older surgical patients. METHODS AND ANALYSIS: Adults ≥60 years undergoing cardiac, orthopaedic or oncological surgery will be enrolled in one of three-linked type 1 hybrid effectiveness/implementation RCTs that will be conducted in tandem with similar methods. In each trial, 100 participants will be randomised to a remotely delivered perioperative behavioural treatment incorporating principles of behavioural activation, compassion and care coordination, and medication optimisation, or enhanced usual care with mental health-related resources for this population. The primary outcome is change in depression and anxiety symptoms assessed with the Patient Health Questionnaire-Anxiety Depression Scale from baseline to 3 months post surgery. Other outcomes include quality of life, delirium, length of stay, falls, rehospitalisation, pain and implementation outcomes, including study and intervention reach, acceptability, feasibility and appropriateness, and patient experience with the intervention. ETHICS AND DISSEMINATION: The trials have received ethics approval from the Washington University School of Medicine Institutional Review Board. Informed consent is required for participation in the trials. The results will be submitted for publication in peer-reviewed journals, presented at clinical research conferences and disseminated via the Center for Perioperative Mental Health website. TRIAL REGISTRATION NUMBERS: NCT05575128, NCT05685511, NCT05697835, pre-results.

A Perioperative Mental Health Intervention for Depressed and Anxious Older Surgical Patients: Results From a Feasibility Study.

OBJECTIVES: The perioperative period is challenging and stressful for older adults. Those with depression and/or anxiety have an increased risk of adverse surgical outcomes. We assessed the feasibility of a perioperative mental health intervention composed of medication optimization and a wellness program following principles of behavioral activation and care coordination for older surgical patients. METHODS: We included orthopedic, oncologic, and cardiac surgical patients aged 60 and older. Feasibility outcomes included study reach, the number of patients who agreed to participate out of the total eligible; and intervention reach, the number of patients who completed the intervention out of patients who agreed to participate. Intervention efficacy was assessed using the Patient Health Questionnaire for Anxiety and Depression (PHQ-ADS). Implementation potential and experiences were collected using patient surveys and qualitative interviews. Complementary caregiver feedback was also collected. RESULTS: Twenty-three out of 28 eligible older adults participated in this study (mean age 68.0 years, 65% women), achieving study reach of 82% and intervention reach of 83%. In qualitative interviews, patients (n = 15) and caregivers (complementary data, n = 5) described overwhelmingly positive experiences with both the intervention components and the interventionist, and reported improvement in managing depression and/or anxiety. Preliminary efficacy analysis indicated improvement in PHQ-ADS scores (F = 12.13, p <0.001). CONCLUSIONS: The study procedures were reported by participants as feasible and the perioperative mental health intervention to reduce anxiety and depression in older surgical patients showed strong implementation potential. Preliminary data suggest its efficacy for improving depression and/or anxiety symptoms. A randomized controlled trial assessing the intervention and implementation effectiveness is currently ongoing.

The STOP COVID 2 Study: Fluvoxamine vs Placebo for Outpatients With Symptomatic COVID-19, a Fully Remote Randomized Controlled Trial.

Background: Prior randomized clinical trials have reported benefit of fluvoxamine ≥200 mg/d vs placebo for patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Methods: This randomized, double-blind, placebo-controlled, fully remote multisite clinical trial evaluated whether fluvoxamine prevents clinical deterioration in higher-risk outpatients with acute coronavirus disease 2019 (COVID-19). Between December 2020 and May 2021, nonhospitalized US and Canadian participants with confirmed symptomatic infection received fluvoxamine (50 mg on day 1, 100 mg twice daily thereafter) or placebo for 15 days. The primary modified intent-to-treat (mITT) population included participants who started the intervention within 7 days of symptom onset with a baseline oxygen saturation ≥92%. The primary outcome was clinical deterioration within 15 days of randomization, defined as having both (1) shortness of breath (severity ≥4 on a 0-10 scale or requiring hospitalization) and (2) oxygen saturation <92% on room air or need for supplemental oxygen. Results: A total of 547 participants were randomized and met mITT criteria (n = 272 fluvoxamine, n = 275 placebo). The Data Safety Monitoring Board recommended stopping early for futility related to lower-than-predicted event rates and declining accrual concurrent with vaccine availability in the United States and Canada. Clinical deterioration occurred in 13 (4.8%) participants in the fluvoxamine group and 15 (5.5%) participants in the placebo group (absolute difference at day 15, 0.68%; 95% CI, -3.0% to 4.4%; log-rank P = .91). Conclusions: This trial did not find fluvoxamine efficacious in preventing clinical deterioration in unvaccinated outpatients with symptomatic COVID-19. It was stopped early and underpowered due to low primary outcome rates. Clinical Trials Registration: ClinicalTrials.gov Identifier: NCT04668950.

Effects of Mindfulness Training and Exercise on Cognitive Function in Older Adults: A Randomized Clinical Trial.

Importance: Episodic memory and executive function are essential aspects of cognitive functioning that decline with aging. This decline may be ameliorable with lifestyle interventions. Objective: To determine whether mindfulness-based stress reduction (MBSR), exercise, or a combination of both improve cognitive function in older adults. Design, Setting, and Participants: This 2 × 2 factorial randomized clinical trial was conducted at 2 US sites (Washington University in St Louis and University of California, San Diego). A total of 585 older adults (aged 65-84 y) with subjective cognitive concerns, but not dementia, were randomized (enrollment from November 19, 2015, to January 23, 2019; final follow-up on March 16, 2020). Interventions: Participants were randomized to undergo the following interventions: MBSR with a target of 60 minutes daily of meditation (n = 150); exercise with aerobic, strength, and functional components with a target of at least 300 minutes weekly (n = 138); combined MBSR and exercise (n = 144); or a health education control group (n = 153). Interventions lasted 18 months and consisted of group-based classes and home practice. Main Outcomes and Measures: The 2 primary outcomes were composites of episodic memory and executive function (standardized to a mean [SD] of 0 [1]; higher composite scores indicate better cognitive performance) from neuropsychological testing; the primary end point was 6 months and the secondary end point was 18 months. There were 5 reported secondary outcomes: hippocampal volume and dorsolateral prefrontal cortex thickness and surface area from structural magnetic resonance imaging and functional cognitive capacity and self-reported cognitive concerns. Results: Among 585 randomized participants (mean age, 71.5 years; 424 [72.5%] women), 568 (97.1%) completed 6 months in the trial and 475 (81.2%) completed 18 months. At 6 months, there was no significant effect of mindfulness training or exercise on episodic memory (MBSR vs no MBSR: 0.44 vs 0.48; mean difference, -0.04 points [95% CI, -0.15 to 0.07]; P = .50; exercise vs no exercise: 0.49 vs 0.42; difference, 0.07 [95% CI, -0.04 to 0.17]; P = .23) or executive function (MBSR vs no MBSR: 0.39 vs 0.31; mean difference, 0.08 points [95% CI, -0.02 to 0.19]; P = .12; exercise vs no exercise: 0.39 vs 0.32; difference, 0.07 [95% CI, -0.03 to 0.18]; P = .17) and there were no intervention effects at the secondary end point of 18 months. There was no significant interaction between mindfulness training and exercise (P = .93 for memory and P = .29 for executive function) at 6 months. Of the 5 prespecified secondary outcomes, none showed a significant improvement with either intervention compared with those not receiving the intervention. Conclusions and Relevance: Among older adults with subjective cognitive concerns, mindfulness training, exercise, or both did not result in significant differences in improvement in episodic memory or executive function at 6 months. The findings do not support the use of these interventions for improving cognition in older adults with subjective cognitive concerns. Trial Registration: ClinicalTrials.gov Identifier: NCT02665481.

Use of an Interactive Obesity Treatment Approach in Individuals With Severe Mental Illness: Feasibility, Acceptability, and Proposed Engagement Criteria.

BACKGROUND: Digital and mobile health interventions are increasingly being used to support healthy lifestyle change, including in certain high-risk populations such as those with severe mental illnesses (SMIs). Life expectancy in this population lags 15 years behind counterparts in the general population, primarily due to obesity-related health conditions. OBJECTIVE: We tested the feasibility and usability of a 12-week interactive obesity treatment approach (iOTA) to adults with chronic SMIs (depression, bipolar disorder and schizophrenia spectrum disorder) receiving treatment in community settings. The iOTA incorporates short message service (SMS) text messages to supplement monthly in-person health coaching. METHODS: Factors hypothesized to be associated with weight change were illness severity and treatment engagement. Severe psychiatric symptoms were defined as baseline Clinical Global Impression severity score of >5. Criterion engagement was defined as a text messaging response rate >80% during the first 4 weeks of treatment. Disordered eating, assessed with the Loss of Control Over Eating Scores, was also evaluated. Participants provided qualitative data, further informing assessment of intervention feasibility, usability, and acceptability. RESULTS: A total of 26 participants were enrolled. The mean age was 48.5 (SD 15.67) years; 40% (10/26) were Black and 60% (15/26) female. Participants with lower symptom severity and adequate engagement demonstrated significantly decreased weight (F1,16=22.54, P<.001). Conversely, high symptom severity and lower text message response rates were associated with trend-level increases in weight (F1,7=4.33, P=.08). Loss-of-control eating was not observed to impact treatment outcome. Participants voiced preference for combination of live health coaching and text messaging, expressing desire for personalized message content. CONCLUSIONS: These results demonstrate the feasibility of delivering an adapted iOTA to SMI patients receiving care in community settings and suggest testable criteria for defining sufficient treatment engagement and psychiatric symptom severity, two factors known to impact weight loss outcomes. These important findings suggest specific adaptations may be needed for optimal treatment outcomes in individuals with SMI.

Covariance and Correlation Analysis of Resting State Functional Magnetic Resonance Imaging Data Acquired in a Clinical Trial of Mindfulness-Based Stress Reduction and Exercise in Older Individuals.

We describe and apply novel methodology for whole-brain analysis of resting state fMRI functional connectivity data, combining conventional multi-channel Pearson correlation with covariance analysis. Unlike correlation, covariance analysis preserves signal amplitude information, which feature of fMRI time series may carry physiological significance. Additionally, we demonstrate that dimensionality reduction of the fMRI data offers several computational advantages including projection onto a space of manageable dimension, enabling linear operations on functional connectivity measures and exclusion of variance unrelated to resting state network structure. We show that group-averaged, dimensionality reduced, covariance and correlation matrices are related, to reasonable approximation, by a single scalar factor. We apply this methodology to the analysis of a large, resting state fMRI data set acquired in a prospective, controlled study of mindfulness training and exercise in older, sedentary participants at risk for developing cognitive decline. Results show marginally significant effects of both mindfulness training and exercise in both covariance and correlation measures of functional connectivity.

Mindfulness-Based Stress Reduction in Older Individuals: Who Benefits the Most?

Background: Preexisting patient characteristics may influence the outcome of mindfulness training, and a composite predictive index may be most informative in predicting outcome. Primary Study Objective: To develop a predictive index from baseline patient characteristics to determine which characteristics are associated with improvement following mindfulness-based stress reduction (MBSR) vs health education and to examine whether intreatment variables-reflecting adherence to the mindfulness intervention-predicted clinical outcome. Methods: In a secondary data analysis, a composite moderator statistical approach created a predictive index from baseline participant characteristics that were associated with clinical global impressions improvement following intervention. Setting: Data come from a 2-site, randomized controlled trial which took place in medical centers in St Louis, Missouri, and San Diego, California. Participants: Included 103 older adults with anxiety and/or depressive disorders randomized to either 8 sessions of MBSR or health education classes. Intervention: MBSR was delivered in 8 sessions of 2 hours each by credentialed health care providers. The control condition consisted of health education classes designed to match the length and timing of the MBSR sessions. Primary Outcome Measures: The Clinical Global Impressions-Improvement scale was used to measure symptom improvement and was assigned by a blind rater. Results: The combined moderator approach generated a predictive index with a moderate effect size (0.46; 95% CI: 0.35, 0.57). Individuals who demonstrated improvement on the scale following MBSR were more likely to be younger, female, with lower psychological symptom severity, and less likely to have a diagnosis of depression or to be taking selective serotonin reuptake inhibitors. Discussion: Baseline characteristics predicted clinical response with MBSR in older adults. These predictive factors, if replicated and validated, could determine which patients are most likely to benefit from mindfulness training and lead to personalized strategies to maximize outcomes. The study was registered on ClinicalTrials.gov (identifier: NCT01693874).

Executive Function Moderates Functional Outcomes of Engagement Strategies During Rehabilitation in Older Adults.

OBJECTIVE: This study examined cognitive, affective, and medical impairments and their impact on rehabilitation approaches for improving functional outcome after hospitalization in older adults. DESIGN: A secondary analysis of a randomized clinical trial in 229 adults 65 yrs or older admitted to two skilled nursing facilities undergoing rehabilitation services was conducted. Patients were randomized to receive physical and occupational therapy by therapists trained in systematic approaches to engage patients, called Enhanced Medical Rehabilitation, or standard of care. The outcome of interest was functional improvement, defined as Barthel Index at discharge (controlling for Barthel Index upon admission). This study analyzed the relationship of measures of cognition, depression, and medical comorbidities as predictors of functional outcome and as moderators interacting with treatment group. RESULTS: Clock drawing score moderated treatment effect size; the functional improvement of Enhanced Medical Rehabilitation over standard of care therapy reduced with increasing executive impairment. In contrast, general cognitive abilities, depression, medical comorbidities, and readiness for rehabilitation were neither predictors nor moderators of functional improvement. CONCLUSIONS: For older adults undergoing rehabilitation, greater functional improvement with the motivational techniques of Enhanced Medical Rehabilitation was contingent on patients having intact executive function. Given that executive function impairments are common in rehabilitation populations, new strategies are needed to improve treatment outcomes in physical/occupational therapy. TO CLAIM CME CREDITS: Complete the self-assessment activity and evaluation online at http://www.physiatry.org/JournalCME. CME OBJECTIVES: Upon completion of this article, the reader should be able to (1) Discuss the role of baseline affective, cognitive, and medical impairments in impacting functional outcomes of older adults undergoing rehabilitation; (2) Describe the behavioral change and motivational approaches that are core features of the novel intervention known as Enhanced Medical Rehabilitation (E-MR); and (3) Determine the role of baseline executive function in moderating the effect of rehabilitation intervention on functional outcomes in older adults. LEVEL: Advanced. ACCREDITATION: The Association of Academic Physiatrists is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.The Association of Academic Physiatrists designates this Journal-based CME activity for a maximum of 1.0 AMA PRA Category 1 Credit(s)™. Physicians should only claim credit commensurate with the extent of their participation in the activity.

Prolonged ketamine infusion modulates limbic connectivity and induces sustained remission of treatment-resistant depression.

Ketamine produces a rapid antidepressant response in over 50% of adults with treatment-resistant depression. A long infusion of ketamine may provide durable remission of depressive symptoms, but the safety, efficacy, and neurobiological correlates are unknown. In this open-label, proof-of-principle study, adults with treatment-resistant depression (N = 23) underwent a 96-h infusion of intravenous ketamine (0.15 mg/kg/h titrated toward 0.6 mg/kg/h). Clonidine was co-administered to reduce psychotomimetic effects. We measured clinical response for 8 weeks post-infusion. Resting-state functional magnetic resonance imaging was used to assess functional connectivity in patients pre- and 2 weeks post-infusion and in matched non-depressed controls (N = 27). We hypothesized that responders to therapy would demonstrate response-dependent connectivity changes while all subjects would show treatment-dependent connectivity changes. Most participants completed infusion (21/23; mean final dose 0.54 mg/kg/h, SD 0.13). The infusion was well tolerated with minimal cognitive and psychotomimetic side effects. Depressive symptoms were markedly reduced (MADRS 29 ± 4 at baseline to 9 ± 8 one day post-infusion), which was sustained at 2 weeks (13 ± 8) and 8 weeks (15 ± 8). Imaging demonstrated a response-dependent decrease in hyperconnectivity of the subgenual anterior cingulate cortex to the default mode network, and a treatment-dependent decrease in hyperconnectivity within the limbic system (hippocampus, amygdala, medial thalamus, nucleus accumbens). In exploratory analyses, connectivity was increased between the limbic system and frontal areas, and smaller right hippocampus volume at baseline predicted larger MADRS change. A single prolonged infusion of ketamine provides a tolerated, rapid, and sustained response in treatment-resistant depression and normalizes depression-related hyperconnectivity in the limbic system and frontal lobe. ClinicalTrials.gov : Treatment Resistant Depression (Pilot), NCT01179009.

Prolactin and Estrogen Levels in Postmenopausal Women Receiving Aripiprazole Augmentation Treatment for Depression.

BACKGROUND: Antipsychotic drugs are well established to alter serum prolactin levels, often resulting in adverse effects including amenorrhea, galactorrhea, osteoporosis, and loss of libido. There is growing preclinical evidence that prolactin-elevating drugs can instigate the progression of precancerous lesions to breast cancer and that genes activated by prolactin are associated with the development and proliferation of breast cancer. Current guides advise a cautious approach (weighing risks and benefits) to the administration of prolactin-elevating antipsychotic drugs in women with a previously detected breast cancer. Aripiprazole is known to be a prolactin-sparing antipsychotic; however, data regarding its effects on prolactin and estrogens in postmenopausal women are lacking. METHODS: We examined serum hormone levels in n = 66 women who participated in a randomized, double-blind, placebo-controlled, multicenter trial of aripiprazole (high and low doses) added to an antidepressant in adults older than 60 years. Aripiprazole or placebo tablets were administered for 12 weeks as an augmentation strategy in venlafaxine-treated women. The primary outcomes were the difference in prolactin and estrogen levels. RESULTS: There was no significant effect of aripiprazole treatment on prolactin or estrogen levels, including in models that divided groups into low and high doses: prolactin (P = 0.075), estrone (P = 0.67), and estradiol (P = 0.96). CONCLUSIONS: Aripiprazole addition to an antidepressant did not alter serum estrogens or prolactin. These findings may be relevant in the treatment of some postmenopausal women with depression.

Fluvoxamine vs Placebo and Clinical Deterioration in Outpatients With Symptomatic COVID-19: A Randomized Clinical Trial.

Importance: Coronavirus disease 2019 (COVID-19) may lead to serious illness as a result of an excessive immune response. Fluvoxamine may prevent clinical deterioration by stimulating the σ-1 receptor, which regulates cytokine production. Objective: To determine whether fluvoxamine, given during mild COVID-19 illness, prevents clinical deterioration and decreases the severity of disease. Design, Setting, and Participants: Double-blind, randomized, fully remote (contactless) clinical trial of fluvoxamine vs placebo. Participants were community-living, nonhospitalized adults with confirmed severe acute respiratory syndrome coronavirus 2 infection, with COVID-19 symptom onset within 7 days and oxygen saturation of 92% or greater. One hundred fifty-two participants were enrolled from the St Louis metropolitan area (Missouri and Illinois) from April 10, 2020, to August 5, 2020. The final date of follow-up was September 19, 2020. Interventions: Participants were randomly assigned to receive 100 mg of fluvoxamine (n = 80) or placebo (n = 72) 3 times daily for 15 days. Main Outcomes and Measures: The primary outcome was clinical deterioration within 15 days of randomization defined by meeting both criteria of (1) shortness of breath or hospitalization for shortness of breath or pneumonia and (2) oxygen saturation less than 92% on room air or need for supplemental oxygen to achieve oxygen saturation of 92% or greater. Results: Of 152 patients who were randomized (mean [SD] age, 46 [13] years; 109 [72%] women), 115 (76%) completed the trial. Clinical deterioration occurred in 0 of 80 patients in the fluvoxamine group and in 6 of 72 patients in the placebo group (absolute difference, 8.7% [95% CI, 1.8%-16.4%] from survival analysis; log-rank P = .009). The fluvoxamine group had 1 serious adverse event and 11 other adverse events, whereas the placebo group had 6 serious adverse events and 12 other adverse events. Conclusions and Relevance: In this preliminary study of adult outpatients with symptomatic COVID-19, patients treated with fluvoxamine, compared with placebo, had a lower likelihood of clinical deterioration over 15 days. However, the study is limited by a small sample size and short follow-up duration, and determination of clinical efficacy would require larger randomized trials with more definitive outcome measures. Trial Registration: ClinicalTrials.gov Identifier: NCT04342663.

A Smartphone-Based Technique to Detect Dynamic User Preferences for Tailoring Behavioral Interventions: Observational Utility Study of Ecological Daily Needs Assessment.

BACKGROUND: Mobile health apps are promising vehicles for delivering scalable health behavior change interventions to populations that are otherwise difficult to reach and engage, such as young adults with psychiatric conditions. To improve uptake and sustain consumer engagement, mobile health interventions need to be responsive to individuals' needs and preferences, which may change over time. We previously created an ecological daily needs assessment to capture microprocesses influencing user needs and preferences for mobile health treatment adaptation. OBJECTIVE: The objective of our study was to test the utility of a needs assessment anchored within a mobile app to capture individualized, contextually relevant user needs and preferences within the framework of a weight management mobile health app. METHODS: Participants with an iOS device could download the study app via the study website or links from social media. In this fully remote study, we screened, obtained informed consent from, and enrolled participants through the mobile app. The mobile health framework included daily health goal setting and self-monitoring, with up to 6 daily prompts to determine in-the-moment needs and preferences for mobile health-assisted health behavior change. RESULTS: A total of 24 participants downloaded the app and provided e-consent (22 female; 2 male), with 23 participants responding to at least one prompt over 2 weeks. The mean length of engagement was 5.6 (SD 4.7) days, with a mean of 2.8 (1.1) responses per day. We observed individually dynamic needs and preferences, illustrating daily variability within and between individuals. Qualitative feedback indicated preferences for self-adapting features, simplified self-monitoring, and the ability to personalize app-generated message timing and content. CONCLUSIONS: The technique provided an individually dynamic and contextually relevant alternative and complement to traditional needs assessment for assessing individually dynamic user needs and preferences during treatment development or adaptation. The results of this utility study suggest the importance of personalization and learning algorithms for sustaining app engagement in young adults with psychiatric conditions. Further study in broader user populations is needed.

Mindfulness, Education, and Exercise for age-related cognitive decline: Study protocol, pilot study results, and description of the baseline sample.

BACKGROUND/AIMS: Age-related cognitive decline is a pervasive problem in our aging population. To date, no pharmacological treatments to halt or reverse cognitive decline are available. Behavioral interventions, such as physical exercise and Mindfulness-Based Stress Reduction, may reduce or reverse cognitive decline, but rigorously designed randomized controlled trials are needed to test the efficacy of such interventions. METHODS: Here, we describe the design of the Mindfulness, Education, and Exercise study, an 18-month randomized controlled trial that will assess the effect of two interventions-mindfulness training plus moderate-to-vigorous intensity exercise or moderate-to-vigorous intensity exercise alone-compared with a health education control group on cognitive function in older adults. An extensive battery of biobehavioral assessments will be used to understand the mechanisms of cognitive remediation, by using structural and resting state functional magnetic resonance imaging, insulin sensitivity, inflammation, and metabolic and behavioral assessments. RESULTS: We provide the results from a preliminary study (n = 29) of non-randomized pilot participants who received both the exercise and Mindfulness-Based Stress Reduction interventions. We also provide details on the recruitment and baseline characteristics of the randomized controlled trial sample (n = 585). CONCLUSION: When complete, the Mindfulness, Education, and Exercise study will inform the research community on the efficacy of these widely available interventions improve cognitive functioning in older adults.

Does patient expectancy account for the cognitive and clinical benefits of mindfulness training in older adults?

OBJECTIVES: Patient expectations of treatment effects could influence neuropsychological and clinical outcomes in clinical trials of behavioral and lifestyle interventions, which could potentially confound the interpretation of findings. Our aim was to examine whether patient expectancy mediated effectiveness of Mindfulness-Based Stress Reduction (MBSR) for improving cognitive function and clinical outcome. METHODS: The present study uses data from a single-blind, multi-site, randomized controlled trial comparing MBSR to a health education attention control in older adults with anxiety and/or depressive disorders and subjective cognitive concerns. Using the Credibility and Expectations Questionnaire, we measured expectancy and perceived credibility of the interventions assigned to patients. Using mediational analysis, we examined the influence of expectancy and credibility on two key outcomes: memory performance and clinical global improvement. RESULTS: Neither expectancy nor perceived credibility of intervention accounted significantly for MBSR's effectiveness for memory test performance or clinical global improvement. CONCLUSION: In this clinical trial, expectancy for improvement did not account for the effectiveness of MBSR on memory performance or clinical outcomes in depressed and anxious older adults. We advise that clinical trials of behavioral and lifestyle interventions for brain health in older adults should measure and test the role of expectancy.

Comorbid anxiety in late-life depression: Relationship with remission and suicidal ideation on venlafaxine treatment.

OBJECTIVE: The purpose of this study was to examine the influence of comorbid anxiety symptoms on antidepressant treatment remission in older adults with major depressive disorder (MDD). METHOD: In this multisite clinical trial, 468 older adults aged 60 years or older with MDD received open-label protocolized treatment with venlafaxine extended release (ER) titrated to a maximum of 300 mg daily. At baseline, anxiety was assessed with the Anxiety Sensitivity Index, the Brief Symptom Inventory (BSI) anxiety subscale, and the Penn State Worry Questionnaire. To measure treatment response, depressive symptoms and suicidality were assessed every 1-2 weeks with the Montgomery-Asberg Depression Rating Scale and the 19-item Scale for Suicide Ideation; anxiety was assessed with the BSI. Logistic regression and survival analysis were used to evaluate whether anxiety symptoms predicted depression remission. We also examined the relationships between anxiety scores and suicidality at baseline. RESULTS: Baseline anxiety symptoms did not predict remission or time to remission of depressive symptoms. Depressive, worry, and panic symptoms decreased in parallel in patients with high anxiety. Anxiety symptoms were associated with the severity of depression and with suicidality. CONCLUSION: In older adults with MDD, comorbid anxiety symptoms are associated with symptom severity but do not affect antidepressant remission or time to remission.

Effect of Enhanced Medical Rehabilitation on Functional Recovery in Older Adults Receiving Skilled Nursing Care After Acute Rehabilitation: A Randomized Clinical Trial.

Importance: Enhanced medical rehabilitation (EMR) is a systematic and standardized approach for physical and occupational therapists to engage patients. Higher patient engagement in therapy might lead to improved functional recovery in rehabilitation settings, such as skilled nursing facilities (SNFs). Objective: To determine whether EMR improves older adults' functional recovery. Design, Setting, and Participants: A double-blind, parallel-group, randomized clinical trial was conducted from July 29, 2014, to July 13, 2018, in 229 adults aged 65 years or older admitted to 2 US SNFs. Participants were randomized to receive EMR (n = 114) vs standard-of-care rehabilitation (n = 115). Intention-to-treat analysis was used. Interventions: The intervention group received their physical and occupational therapy from therapists trained in EMR. Based on models of motivation and behavior change, EMR is a toolkit of techniques to increase patient engagement and therapy intensity. The control group received standard-of-care rehabilitation from physical and occupational therapists not trained in EMR. Main Outcomes and Measures: The primary outcome was change in function in activities of daily living and mobility, as assessed with the Barthel Index, which measures 10 basic activities of daily living or mobility items (scale range, 0-100), from SNF admission to discharge; secondary outcomes were gait speed for 10 m, 6-minute walk test, discharge disposition, rehospitalizations, and self-reported functional status at days 30, 60, and 90. To examine the rehabilitation process, therapists' engagement with patients and patient active time during therapy were measured for a sample of the sessions. Results: Of the 229 participants, 149 (65.1%) were women; 177 (77.3%) were white, and 51 (22.3%) were black; mean (SD) age was 79.3 (8.0) years. Participants assigned to EMR showed greater recovery of function than those assigned to standard of care (mean increase in Barthel Index score, 35 points; 95% CI, 31.6-38.3 vs 28 points; 95% CI, 25.2-31.7 points; P = .007). There was no evidence of a difference in the length of stay (mean [SD], 23.5 [13.1] days). However, there were no group by time differences in secondary outcome measures, including self-reported function after SNF discharge out to 90 days as measured on the Barthel Index (mean [SE] score: EMR, 83.65 [2.20]; standard of care, 84.67 [2.16]; P = .96). The EMR therapists used a median (interquartile range) of 24.4 (21.0-37.3) motivational messages per therapy session vs 2.3 (1.1-2.9) for nontrained therapists (P < .001), and EMR patients were active during a mean (SD) of 52.5 (6.6%) of the therapy session time vs 41.2 (6.8%) for nontrained therapists (P = .001). Conclusions and Relevance: Enhanced medical rehabilitation modestly improved short-term functional recovery for selected older adults rehabilitating in SNFs. However, there was no evidence that the benefits persisted over the longer term. This study demonstrates the value of engaging and motivating older adults in rehabilitation therapy, but more work is needed to extend these benefits to longer-term outcomes after discharge home. Trial Registration: ClinicalTrials.gov identifier: NCT02114879.

Adiposity, Hepatic Triglyceride, and Carotid Intima Media Thickness During Behavioral Weight Loss Treatment in Antipsychotic-Treated Youth: A Randomized Pilot Study.

Objectives: The purpose of this pilot study was to evaluate changes in adiposity, carotid intima media thickness (CIMT), and hepatic fat content measured via magnetic resonance imaging-estimated hepatic proton density fat fraction (PDFF) in antipsychotic (AP)-treated youth versus nonpsychiatric (NP) participants during participation in a 16-week behavioral weight loss (BWL) intervention. Subjects/Methods: Overweight/obese AP-treated youth (n = 26) were randomized 2:1 to weekly treatment versus recommended care (RC) over 16 weeks. NP controls (n = 21) were assigned to weekly treatment. Dual-energy X-ray absorptiometry (DEXA)-measured adiposity, CIMT, and PDFF were measured at baseline and 16 weeks. Analyses assessed group differences in the effect of BWL on adiposity, CIMT, and PDFF. Results: BWL was well tolerated in both AP-treated and NP groups. DEXA-measured fat decreased significantly in the NP group (F[1,16] = 11.81, p = 0.003), with modest improvements in adiposity and hepatic fat in the AP-treated group, while an increase in adiposity was observed in the RC group. Significant differences in endpoint DEXA total fat (F[2,34] = 4.81, p = 0.01) and PDFF (F[2,30] = 3.60, p = 0.04) occurred across treatment groups, explained by larger improvements in NP versus RC youth in DEXA total fat (p = 0.03) and PDFF (p = 0.04). Conclusions: Intensive, family-based BWL treatment can improve whole-body adiposity and liver fat in obese youth, with decreases or attenuation of additional fat gain observed in AP-treated youth.

Metabolic Effects of Antipsychotics on Adiposity and Insulin Sensitivity in Youths: A Randomized Clinical Trial.

Importance: Antipsychotic medications are commonly used to treat nonpsychotic disruptive behavioral disorders in youths. Objective: To characterize the metabolic effects of first exposure to antipsychotics in youths using criterion standard assessments of body composition and insulin sensitivity. Design, Setting, and Participants: This randomized clinical trial recruited antipsychotic-naive youths aged 6 to 18 years in the St Louis, Missouri, metropolitan area who were diagnosed with 1 or more psychiatric disorders and clinically significant aggression and in whom antipsychotic treatment was considered. Participants were enrolled from June 12, 2006, through November 10, 2010. Enrolled participants were randomized (1:1:1) to 1 of 3 antipsychotics commonly used in children with disruptive behavioral disorders and evaluated for 12 weeks. Data were analyzed from January 17, 2011, through August 9, 2017. Interventions: Twelve weeks of treatment with oral aripiprazole (n = 49), olanzapine (n = 46), or risperidone (n = 49). Main Outcomes and Measures: Primary outcomes included percentage total body fat measured by dual-energy x-ray absorptiometry (DXA) and insulin sensitivity in muscle measured via hyperinsulinemic clamps with stable isotopically labeled tracers. Secondary outcomes included abdominal adiposity measured by magnetic resonance imaging (MRI) and adipose and hepatic tissue insulin sensitivity measured via clamps with tracers. Results: The intention-to-treat sample included 144 participants (98 males [68.1%]; mean [SD] age, 11.3 [2.8] years); 74 (51.4%) were African American, and 43 (29.9%) were overweight or obese at baseline. For the primary outcomes, from baseline to week 12, DXA percentage total body fat increased by 1.18% for risperidone, 4.12% for olanzapine, and 1.66% for aripiprazole and was significantly greater for olanzapine than risperidone or aripiprazole (time by treatment interaction P < .001). From baseline to week 12, insulin-stimulated change in glucose rate of disappearance increased by 2.30% for risperidone and decreased by 29.34% for olanzapine and 30.26% for aripiprazole, with no significant difference across medications (time by treatment interaction, P < .07). This primary measure of insulin sensitivity decreased significantly during 12 weeks in the pooled study sample (effect of time, F = 17.38; P < .001). For the secondary outcomes from baseline to week 12, MRI measured abdominal fat increased, with subcutaneous fat increase significantly greater for olanzapine than risperdone or aripiprazole (time by treatment, P = .003). Behavioral improvements occurred with all treatments. Conclusions and Relevance: Adverse changes in adiposity and insulin sensitivity were observed during 12 weeks of antipsychotic treatment in youths, with the greatest fat increases on olanzapine. Such changes, likely attributable to treatment, may be associated with risk for premature cardiometabolic morbidity and mortality. The results inform risk-benefit considerations for antipsychotic use in youths. Trial Registration: ClinicalTrials.gov identifier: NCT00205699.

Assessment and Treatment of Pediatric Sleep Problems: Knowledge, Skills, Attitudes and Practices in a Group of Community Child Psychiatrists.

As part of a university-based quality improvement project, we aimed to evaluate child psychiatrists' knowledge, skills, attitudes, and practices regarding assessment and treatment of pediatric sleep problems. We developed a nine-question survey of knowledge, skills, attitudes, and practices regarding assessing for and treating sleep complaints in pediatric patients, and administered this survey to child psychiatrists in training and in practice in the state of Missouri. Respondents reported sleep hygiene as the first-line treatment strategy, followed by the use of supplements or over-the-counter remedies. The most common barriers to evidence-based assessment and treatment of sleep problems were the lack of ability to obtain reliable history, and parental preference for medications over behavioral approaches for sleep concerns. These results suggest potential opportunities for enhancing knowledge regarding validated assessment tools and non-pharmacological treatment options for sleep problems. Additional research is needed to further assess the quality and type of sleep education provided in child psychiatry training programs.

Behavioral Weight Loss Treatment in Antipsychotic Treated Youth.

BACKGROUND: Antipsychotic-treated youth have increased risk for the development of obesity and type 2 diabetes. Behavioral weight loss treatments show promise in reducing obesity and diabetes risk in antipsychotic treated adults, but have received no study in antipsychotic treated youth. OBJECTIVE: We describe a rationale for behavioral weight loss interventions in high-weight antipsychotic treated youth, and report behavioral, anthropomorphic, and metabolic findings from a case series of obese antipsychotic-treated adolescents participating in a short-term, family-based behavioral weight loss intervention. METHODS: We adapted the Traffic Light Plan, a 16-week family-based weight loss intervention that promotes healthy energy balance using the colors of the traffic light to categorize the nutritional value of foods and intensity of physical activity, adapting a social ecological framework to address health behavior change in multiple social contexts. The intervention was administered to three obese adolescents with long-term antipsychotic medication exposure. Efficacy of the intervention was evaluated with a battery of anthropomorphic and metabolic assessments including weight, body mass index percentile, whole body adiposity, liver fat content, and fasting plasma glucose and lipids. Participants and their parents also filled out a treatment satisfaction questionnaire upon study completion. RESULTS: Two males and 1 female (all aged 14 years) participated. All 3 participants attended all 16 sessions, and experienced beneficial changes in adiposity, fasting lipids and liver fat content associated with weight stabilization or weight loss. Adolescents and their parents all reported a high level of satisfaction with the treatment. CONCLUSIONS: Family-based behavioral weight loss treatment can be feasibly delivered and is acceptable to antipsychotic-treated youth and their families. Randomized controlled trials are needed to fully evaluate the effectiveness and acceptability of behavioral weight loss interventions in antipsychotic treated youth and their families.