Characterizing Longitudinal Patterns in Cognition, Mood, And Activity in Depression With 6-Week High-Frequency Wearable Assessment: Observational Study.

BACKGROUND: Cognitive symptoms are an underrecognized aspect of depression that are often untreated. High-frequency cognitive assessment holds promise for improving disease and treatment monitoring. Although we have previously found it feasible to remotely assess cognition and mood in this capacity, further work is needed to ascertain the optimal methodology to implement and synthesize these techniques. OBJECTIVE: The objective of this study was to examine (1) longitudinal changes in mood, cognition, activity levels, and heart rate over 6 weeks; (2) diurnal and weekday-related changes; and (3) co-occurrence of fluctuations between mood, cognitive function, and activity. METHODS: A total of 30 adults with current mild-moderate depression stabilized on antidepressant monotherapy responded to testing delivered through an Apple Watch (Apple Inc) for 6 weeks. Outcome measures included cognitive function, assessed with 3 brief n-back tasks daily; self-reported depressed mood, assessed once daily; daily total step count; and average heart rate. Change over a 6-week duration, diurnal and day-of-week variations, and covariation between outcome measures were examined using nonlinear and multilevel models. RESULTS: Participants showed initial improvement in the Cognition Kit N-Back performance, followed by a learning plateau. Performance reached 90% of individual learning levels on average 10 days after study onset. N-back performance was typically better earlier and later in the day, and step counts were lower at the beginning and end of each week. Higher step counts overall were associated with faster n-back learning, and an increased daily step count was associated with better mood on the same (P<.001) and following day (P=.02). Daily n-back performance covaried with self-reported mood after participants reached their learning plateau (P=.01). CONCLUSIONS: The current results support the feasibility and sensitivity of high-frequency cognitive assessments for disease and treatment monitoring in patients with depression. Methods to model the individual plateau in task learning can be used as a sensitive approach to better characterize changes in behavior and improve the clinical relevance of cognitive data. Wearable technology allows assessment of activity levels, which may influence both cognition and mood.

A Descriptive Study of the Caregiver's Experience of Managing Care for Children and Adolescents With Attention-Deficit/Hyperactivity Disorder During the COVID-19 Pandemic: The UNCOVER Study.

Objective: To assess the perceived impact of the COVID-19 pandemic on treatment and quality of life for children and adolescents in the United States who have attention-deficit/hyperactivity disorder (ADHD).Methods: An online survey of members of PatientsLikeMe was conducted via the health-tracking platform between March 10 and April 2, 2021. Participants were adult caregivers of dependents aged 6-18 years with diagnosed ADHD and who were taking or not taking prescription medication for ADHD.Results: The study enrolled 37 adult caregivers of 37 children/adolescents; 36 caregivers responded to treatment questions for children/adolescents. Twenty were caregivers to dependents currently being treated for ADHD. Compared with before the pandemic, there was a decrease in the percentage of children/adolescents using prescription ADHD medication from 65% to 54% during the pandemic. At least 1 switch in ADHD medication and a dosage change were reported by 5 and 8 caregivers, respectively. Seven caregivers reported their dependents had had difficulty adhering to their medication regimen during the pandemic, which caregivers ascribed to a lack of a structured routine. Telehealth visits for their dependents were reported by 13 caregivers. None of the caregivers of dependents taking ADHD medication reported a major impact of the pandemic on ADHD-related medical care. Irrespective of treatment status, 17 caregivers reported that their dependents had ADHD management goals and agreed that the pandemic had a negative impact on progress toward those goals.Conclusions: Many caregivers of children/adolescents with ADHD found it challenging to manage their dependents' symptoms and treatment during the pandemic.Prim Care Companion CNS Disord 2024;26(1):23m03587. Author affiliations are listed at the end of this article.

Real-world clinical outcomes and treatment patterns in patients with MDD treated with vortioxetine: a retrospective study.

BACKGROUND: This study included evaluation of the effectiveness of vortioxetine, a treatment for adults with major depressive disorder (MDD), using patient-reported outcome measures (PROMs) in a real-world setting. METHODS: This retrospective chart review analyzed the care experiences of adult patients with a diagnosis of MDD from Parkview Physicians Group - Mind-Body Medicine, Midwestern United States. Patients with a prescription for vortioxetine, an initial baseline visit, and ≥ 2 follow-up visits within 16 weeks from September 2014 to December 2018 were included. The primary outcome measure was effectiveness of vortioxetine on depression severity as assessed by change in Patient Health Questionnaire-9 (PHQ-9) scores ~ 12 weeks after initiation of vortioxetine. Secondary outcomes included changes in depression-related symptoms (i.e., sexual dysfunction, sleep disturbance, cognitive function, work/social function), clinical characteristics, response, remission, and medication persistence. Clinical narrative notes were also analyzed to examine sleep disturbance, sexual dysfunction, appetite, absenteeism, and presenteeism. All outcomes were examined at index (start of vortioxetine) and at ~ 12 weeks, and mean differences were analyzed using pairwise t tests. RESULTS: A total of 1242 patients with MDD met inclusion criteria, and 63.9% of these patients had ≥ 3 psychiatric diagnoses and 65.9% were taking ≥ 3 medications. PHQ-9 mean scores decreased significantly from baseline to week 12 (14.15 ± 5.8 to 9.62 ± 6.03, respectively; p < 0.001). At week 12, the response and remission rates in all patients were 31.0% and 23.1%, respectively, and 67% continued vortioxetine treatment. Overall, results also showed significant improvements by week 12 in anxiety (p < 0.001), sexual dysfunction (p < 0.01), sleep disturbance (p < 0.01), cognitive function (p < 0.001), work/social functioning (p = 0.021), and appetite (p < 0.001). A significant decrease in presenteeism was observed at week 12 (p < 0.001); however, no significant change was observed in absenteeism (p = 0.466). CONCLUSIONS: Using PROMs, our study results suggest that adults with MDD prescribed vortioxetine showed improvement in depressive symptoms in the context of a real-world clinical practice setting. These patients had multiple comorbid psychiatric and physical diagnoses and multiple previous antidepressant treatments had failed.

The Experience of Adults With Attention-Deficit/Hyperactivity Disorder in 2021 During the COVID-19 Pandemic: The UNCOVER Study.

Background: This study surveyed adults with attention-deficit/hyperactivity disorder (ADHD) to understand the impact of the COVID-19 pandemic on aspects of their disorder, quality of life, and treatment experience.Methods: A cross-sectional survey of US-resident members of PatientsLikeMe (PLM) was conducted through the PLM health tracking platform between March 10 and April 2, 2021. Adult participants with self-reported ADHD currently taking prescription medication (treated) and those not taking medication (untreated) were enrolled.Results: The study included 93 adults, of whom 48 patients were taking medication for ADHD. Most of the 45 untreated patients were not taking medication for reasons unrelated to the pandemic. Of the 47 treated patients who also completed the survey, 22 patients had ≥ 1 switch in ADHD medication type, and nearly half had a dosage change during the pandemic. Further, 29 treated patients reported a negative impact of the pandemic on their daily ADHD medication routine, primarily due to a "lack of schedule" and "changes to structured routine," and 16 patients reported "increased difficulty" adhering to prescribed ADHD medication during the pandemic compared with before the pandemic. Of the total study population, 52 patients reported having a telehealth visit during the pandemic, and 38 patients had an ADHD management goal. All but 1 patient with an ADHD management goal reported a negative impact of the pandemic on progress toward their goal. More treated patients than untreated adults reported having control over bothersome ADHD symptoms.Conclusions: Adults with ADHD reported increased difficulty in managing their symptoms during the COVID-19 pandemic.Prim Care Companion CNS Disord 2023;25(4):22m03474. Author affiliations are listed at the end of this article.

User-Centered Design of a Digitally Enabled Care Pathway in a Large Health System: Qualitative Interview Study.

BACKGROUND: Major depressive disorder (MDD) is a leading cause of disability worldwide. Management of chronic conditions such as MDD can be improved by enhanced patient engagement, measurement-based care (MBC), and shared decision-making (SDM). A user-centered design approach can improve the understanding of the patient journey and care team workflows and thus aid the development of digital health care innovations optimized for the needs of patients living with MDD and their primary care teams. OBJECTIVE: This study aims to use qualitative research methods for the user-centered design of a digitally enabled MDD care platform, PathwayPlatform, intended to enhance patient engagement, MBC, and SDM. METHODS: Insights were gathered through 2 stages of qualitative interviews by a study team with expertise in qualitative research and user-centered design methods. Thematic analysis was used to generate an overarching understanding of a set of shared experiences, thoughts, or behaviors across a broad qualitative data set, including transcripts of interviews, to allow both inductive and deductive insights to emerge. Thematic analysis of interviews was supported by Dedoose (SocioCultural Research Consultants, LLC), a qualitative data analysis software tool that enables systematized coding. Findings and insights were presented based on code frequency, salience, and relevance to the research project. RESULTS: In stage 1, interviews were conducted with 20 patients living with MDD and 15 health care providers from September 2018 to January 2019 to understand the experiences with and perceptions about the initial functionality of the Pathway app while also exploring the perceptions about potential additional features and functionality. Feedback about care team workflows and treatment approaches was collected in stage-2 interviews with 36 health care providers at 8 primary care sites. Inductive and deductive thematic analyses revealed several themes related to app functionality, patient-provider engagement, workflow integration, and patient education. Both patients and their care teams perceived the remote tracking of patient-reported outcomes via digital tools to be clinically useful and reliable and to promote MBC and SDM. However, there was emphasis on the need to enhance the flow of real-time data shared with the care team, improve trend visualizations, and integrate the data within the existing clinical workflow and educational programs for patients and their care teams. User feedback was incorporated into the iterative development of the Pathway app. CONCLUSIONS: Ongoing communication with patients living with MDD and their care teams provided an opportunity for user-centric developmental iterations of the Pathway Platform. Key insights led to further development of the patient-facing and care team-facing visit preparation features, collaborative goal-setting and goal-tracking features, patient-reported outcome summaries, and trend visualizations. The result is an enhanced digital platform with the potential to improve treatment outcomes and provide patients living with MDD additional support throughout their treatment journey.

Design and Implementation of a Digitally Enabled Care Pathway to Improve Management of Depression in a Large Health Care System: Protocol for the Implementation of a Patient Care Platform.

BACKGROUND: Major depressive disorder (MDD) is a serious public health concern worldwide. A treatment approach that incorporates measurement-based care (MBC) and shared decision-making between patients with MDD and their providers may foster patient engagement and improve clinical outcomes. While digital tools such as mobile apps show promise for expanding health interventions, these apps are rarely integrated into clinical practice. OBJECTIVE: The primary objective of this ongoing study is to determine whether implementation of a digital tool-the Pathway Platform-in primary care improves adherence to MBC practices; here, we present the study methods. METHODS: This large-scale, real-world implementation study is based on a pilot study of an earlier iteration of a mobile app (the Pathway app) that confirmed the feasibility of using the app in patients with MDD and showed a positive trend in patient engagement in the app arm. In addition, a user-centered design approach that included qualitative assessments from patients and providers was used to improve understanding of the patient journey and care team workflows. User feedback highlighted the need for enhanced features, education modules, and real-time data sharing via integration with the electronic health record. The current iteration of the Platform includes the newest version of the Pathway app, education modules for both patients and providers, and real-time patient-level data sharing with the electronic health record. The study takes place in primary care sites within the Advocate Aurora Health system in Illinois and includes adult patients with MDD who were recently prescribed monotherapy antidepressant medication (defined as a new start, medication switch, or dose change in the past 3 months). Clinical performance and selected patient outcomes will be compared before and after the implementation of the Platform. RESULTS: Patient recruitment was completed in July 2022, with initial results expected in mid-2023. CONCLUSIONS: This study will provide useful insights into real-world integration of a digital platform within a large health system. The methods presented here highlight the unique user-centric development of the Pathway Platform, which has resulted in an enhanced digital tool with the potential to foster MBC and shared decision-making, improve patient-provider communication, and ultimately lead to optimized treatment outcomes for patients with MDD. TRIAL REGISTRATION: ClinicalTrials.gov NCT04891224; https://clinicaltrials.gov/ct2/show/NCT04891224. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/43788.

Design of a real-world, prospective, longitudinal, observational study to compare vortioxetine with other standard of care antidepressant treatments in patients with major depressive disorder: a PatientsLikeMe survey.

BACKGROUND: Major depressive disorder (MDD) is a recurrent psychiatric condition that presents challenges in responding to treatment and achieving long-term remission. To improve outcomes, a shared decision-making treatment approach with patient and healthcare practitioner (HCP) engagement is vital. PatientsLikeMe (PLM), a peer community of patients, provides information on MDD, symptoms, and treatment through forums and resources, helping patients stay engaged in their treatment journey. Data on PLM can be harnessed to gain insights into patient perspectives on MDD symptom management, medication switches, and treatment goals and measures. METHODS: This ongoing, decentralized, longitudinal, observational, prospective study is being conducted using the PLM platform in two parts, enrolling up to 500 patients with MDD in the United States aged ≥ 18 years to compare vortioxetine with other monotherapy antidepressants. The first qualitative component consists of a webinar and discussion forum with PLM community members with MDD, followed by a pilot for functionality testing to improve the study flow and questions in the quantitative survey. The quantitative component follows on the PLM platform, utilizing patient-reported assessments, over a 24-week period. Three surveys will be conducted at baseline and weeks 12 and 24 to collect data on patient global impression of improvement, depression severity, cognitive function, quality of life (QoL) and well-being, medication satisfaction, emotional blunting, symptoms of anhedonia and resilience, as well as goal attainment. Quantitative results will be compared between groups. The qualitative component is complete; patient recruitment is underway for the quantitative component, with results expected in late 2023. DISCUSSION: These results will help HCPs understand patient perspectives on the effectiveness of vortioxetine versus other monotherapy antidepressants in alleviating symptoms of MDD and improvements in QoL. Data from the PLM platform will support a patient goal-based treatment approach, as results can be shared by patients with their HCPs, providing them with insights on patient-centric goals, treatment management and adherence, as well as allowing them to observe changes in patient-related outcomes scores. Findings from the study will also help to optimize the PLM platform to build scalable solutions and connectivity within the community to better serve patients with MDD.

Longitudinal study to assess antidepressant treatment patterns and outcomes in individuals with depression in the general population.

BACKGROUND: Major depressive disorder (MDD) is largely managed in primary care, but physicians vary widely in their understanding of symptoms and treatments. This study aims to better understand the evolution of depression from initial diagnosis over a 3-year period. METHODS: This was a noninterventional, retrospective, longitudinal study, with 2 waves of participant interviews approximately 3 years apart. Phone interviews were conducted using the hybrid artificial intelligence (AI) Sleep-EVAL system, an AI-driven diagnostic deep learning tool. Participants were noninstitutionalized adults representative of the general population in 8 US states. Diagnosis was confirmed according to the DSM-5 using the Sleep-EVAL System. RESULTS: 10,931 participants completed Wave 1 and 2 (W1, W2) interviews. The prevalence of MDD, including partial and complete remission, was 13.4 % and 19.6 % in W1 and W2, respectively. About 42 % of MDD participants at W1 continued to report depressive symptoms at W2. Approximately half of antidepressant (AD) users in W1 were moderately to completely dissatisfied with their treatment; 29.6 % changed their AD for a different one, with 16.4 % switching from one SSRI to another between W1 and W2. Primary care physicians were the top AD prescribers, both in W1 (45.7 %) and W2 (59%), respectively. LIMITATIONS: Data collected relied on self-reporting by participants. As such, the interpretation of the data may be limited. CONCLUSIONS: Depression affects a sizeable portion of the US population. Dissatisfaction with treatment, frequent switching of ADs, and changing care providers are associated with low rates of remission. Residual symptoms remain a challenge that future research must address.

Mobile App to Enhance Patient Activation and Patient-Provider Communication in Major Depressive Disorder Management: Collaborative, Randomized Controlled Pilot Study.

BACKGROUND: Enhanced patient-provider engagement can improve patient health outcomes in chronic conditions, including major depressive disorder (MDD). OBJECTIVE: We evaluated the impact of a digitally enabled care mobile app, Pathway, designed to improve MDD patient-provider engagement. Patients used a mobile interface to assess treatment progress and share this information with primary care providers (PCPs). METHODS: In this 52-week, real-world effectiveness and feasibility study conducted in primary care clinics, 40 patients with MDD who were recently prescribed antidepressant monotherapy were randomized to use a mobile app with usual care (20/40, 50%) or usual care alone (20/40, 50%). Patients in the app arm engaged with the app daily for 18 weeks; a report was generated at 6-week intervals and shared with the PCPs to facilitate shared treatment decision-making discussions. The patients discontinued the app at week 18 and were followed through year 1. Coprimary outcome measures, assessed via research visits, included change from baseline in the 13-item Patient Activation Measure (PAM-13) and 7-item Patient-Provider Engagement Scale scores at week 18. Additional outcome measures included depression severity (9-item Patient Health Questionnaire [PHQ-9]) and cognitive symptoms (5-item Perceived Deficits Questionnaire-Depression). RESULTS: All 37 patients (app arm: n=18, 49%; usual care arm: n=19, 51%) who completed the 18-week follow-up period (n=31, 84% female, mean age 36, SD 11.3 years) had moderate to moderately severe depression. Improvements in PAM-13 and PHQ-9 scores were observed in both arms. Increases in PAM-13 scores from baseline to 18 weeks were numerically greater in the app arm than in the usual care arm (mean 10.5, SD 13.2 vs mean 8.8, SD 9.4; P=.65). At 52 weeks, differences in PAM-13 scores from baseline demonstrated significantly greater improvements in the app arm than in the usual care arm (mean 20.2, SD 17.7 vs mean 1.6, SD 14.2; P=.04). Compared with baseline, PHQ-9 scores decreased in both the app arm and the usual care arm at 18 weeks (mean 7.8, SD 7.2 vs mean 7.0, SD 6.5; P=.73) and 52 weeks (mean 9.5, SD 4.0 vs mean 4.7, SD 6.0; P=.07). Improvements in 7-item Patient-Provider Engagement Scale and WHO-5 scores were observed in both arms at 18 weeks and were sustained through 52 weeks in the app arm. Improvements in WHO-5 scores at 52 weeks were significantly greater in the app arm than in the usual care arm (41.5 vs 20.0; P=.02). CONCLUSIONS: Patients with MDD will engage with a mobile app designed to track treatment and disease progression. PCPs will use the data generated as part of their assessment to inform clinical care. The study results suggest that an app-enabled clinical care pathway may enhance patient activation and benefit MDD management. TRIAL REGISTRATION: ClinicalTrials.gov NCT03242213; https://clinicaltrials.gov/ct2/show/NCT03242213.

An App-Based Digit Symbol Substitution Test for Assessment of Cognitive Deficits in Adults With Major Depressive Disorder: Evaluation Study.

BACKGROUND: Cognitive dysfunction is an impairing core symptom of depression. Among adults with major depressive disorder (MDD) treated with antidepressants, residual cognitive symptoms interfere with patient-reported outcomes. The foregoing characterization of cognitive symptoms provides the rationale for screening and assessing the severity of cognitive symptoms at point of care. However, clinical neurocognitive assessments are time-consuming and difficult, and they require specialist expertise to interpret them. A smartphone-delivered neurocognitive test may offer an effective and accessible tool that can be readily implemented into a measurement-based care framework. OBJECTIVE: We aimed to evaluate the use of a smartphone-delivered app-based version of the established Cognition Kit Digit Symbol Substitution Test (DSST) neurocognitive assessment compared to a traditional paper-and-pencil version. METHODS: Convergent validity and test-retest reliability of the 2 versions were evaluated. Patient satisfaction with the app was also assessed. RESULTS: Assessments made using the app-based Cognition Kit DSST were highly correlated with the standard paper-and-pencil version of the test, both at the baseline visit (r=0.69, df=27; P<.001) and at the end-of-study visit (r=0.82, df=27; P<.001), and they were positively evaluated by 30 patients as being user-friendly, easy to navigate, and preferable over the paper-and-pencil version of the DSST. However, although the app-based Cognition Kit DSST was validated in patients with MDD, it still needs to be evaluated in healthy controls. CONCLUSIONS: App-based DSST may facilitate a more personalized, convenient, and cost-effective method of cognitive assessment, helping to guide measurement-based care and psychotherapeutic and pharmacologic treatment options for patients with MDD. TRIAL REGISTRATION: ClinicalTrials.gov NCT03999567; https://tinyurl.com/2p8pnyv7.

Using the Goal Attainment Scale adapted for depression to better understand treatment outcomes in patients with major depressive disorder switching to vortioxetine: a phase 4, single-arm, open-label, multicenter study.

BACKGROUND: Major depressive disorder (MDD) is the leading cause of disability worldwide. Response to pharmacologic treatment is generally evaluated by traditional clinician- and patient-reported rating scales. Assessing therapeutic efficacy using the Goal Attainment Scale offers a complementary measure that focuses on recovery-oriented outcomes that patients consider valuable and vital to their well-being. This study aimed to examine outcomes using the Goal Attainment Scale adapted for depression (GAS-D). METHODS: A phase 4, single-arm, open-label, multicenter study enrolled patients with MDD who were switching antidepressant medication. Patients received vortioxetine 10-20 mg over 12 weeks. Three specific, measurable, attainable, relevant, and time-bound goals were collaboratively set by patients with their clinicians. One goal was determined by the patient's self-defined objectives; 2 were related to predefined domain categories. Prespecified domains included psychological, motivational, emotional, physical/functional, and cognitive categories. The primary endpoint was the proportion of patients who achieved a GAS-D score ≥ 50 at week 12. Secondary and exploratory endpoints included changes from baseline in several clinical and patient-reported measures of depression and cognitive function. Safety and tolerability were also assessed. RESULTS: At week 12, of the 122 adults participating in the study, 57.8% achieved a GAS-D score ≥ 50. Depression severity, cognitive function, cognitive performance, well-being, employment, and quality of life also significantly improved. Treatment response and remission rates were 65 and 40%, respectively. Vortioxetine was well tolerated, with adverse events consistent with product labeling. CONCLUSIONS: A majority of patients with MDD switching to vortioxetine achieved their treatment goals, including improvement in specific functional outcomes relating to physical and emotional goals, as assessed by the GAS-D and standard patient- and clinician-reported measures. When assayed for convergent validity in a separate analysis, changes in goal scores on the GAS-D were statistically significantly correlated with multiple commonly used clinical measures of depression assessed in this study. The GAS-D approach provides a new patient-centric paradigm for the collaborative development and assessment of progress toward meaningful treatment goals, contributing to a comprehensive evaluation of treatment outcomes in patients with MDD. Longer studies against a control intervention are justified. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02972632 . Registered 21 November 2016.

Adherence and persistence among patients with major depressive disorder enrolled in the vortioxetine tAccess Patient Support Program.

OBJECTIVE: The tAccess Patient Support Program (PSP) is a personalized support program for patients prescribed vortioxetine therapy. We assessed the impact of the tAccess PSP on adherence to and persistence with vortioxetine among adult patients with major depressive disorder (MDD). METHODS: A retrospective observational cohort study was conducted in patients with MDD receiving vortioxetine who were enrolled in the tAccess PSP. Eligible patients were 18 to 64 years of age and had ≥1 vortioxetine claim and ≥1 inpatient/outpatient medical MDD claim during the 12 months preceding or on the index date, defined as the date of the earliest vortioxetine claim. Study outcomes included medication adherence (proportion of days covered [PDC], adherent ≥80%) and persistence (the total number of days on therapy without a ≥30-day gap) at 90, 180, and 365 days. Additionally, persistence was reported for a subset of patients meeting the standardized Healthcare Effectiveness Data and Information Set (HEDIS) Antidepressant Medication Management (AMM) criteria (the percentage of adults aged 18-64 years who remained on an antidepressant for ≥84 days or ≥180 days), as defined by the National Committee for Quality Assurance. These data were reviewed alongside current HEDIS AMM data for commercially insured patients meeting the standardized metric. RESULTS: The study identified a total of 2635 patients with an MDD diagnosis and ≥90 days of follow-up time and a subset of 2238 patients meeting HEDIS AMM criteria. Mean PDC among all patients with MDD was 0.78, with 58.3% of patients achieving PDC ≥80%. During the 90-day follow-up, 62.1% of patients with MDD were persistent on vortioxetine. Among the subset of patients who met HEDIS AMM criteria, persistence was 83.4% and 69.9% at 84 and 180 days, respectively. In comparison, in 2017, HEDIS AMM criteria for antidepressant persistence were met by 67.8% of commercially insured patients at 84 days and 51.8% at 180 days. CONCLUSIONS: These initial results, reviewed alongside recent available HEDIS AMM data, suggest that the tAccess PSP may be beneficial in addressing treatment adherence and persistence in patients with MDD.

Wearable Technology for High-Frequency Cognitive and Mood Assessment in Major Depressive Disorder: Longitudinal Observational Study.

BACKGROUND: Cognitive symptoms are common in major depressive disorder and may help to identify patients who need treatment or who are not experiencing adequate treatment response. Digital tools providing real-time data assessing cognitive function could help support patient treatment and remediation of cognitive and mood symptoms. OBJECTIVE: The aim of this study was to examine feasibility and validity of a wearable high-frequency cognitive and mood assessment app over 6 weeks, corresponding to when antidepressant pharmacotherapy begins to show efficacy. METHODS: A total of 30 patients (aged 19-63 years; 19 women) with mild-to-moderate depression participated in the study. The new Cognition Kit app was delivered via the Apple Watch, providing a high-resolution touch screen display for task presentation and logging responses. Cognition was assessed by the n-back task up to 3 times daily and depressed mood by 3 short questions once daily. Adherence was defined as participants completing at least 1 assessment daily. Selected tests sensitive to depression from the Cambridge Neuropsychological Test Automated Battery and validated questionnaires of depression symptom severity were administered on 3 occasions (weeks 1, 3, and 6). Exploratory analyses examined the relationship between mood and cognitive measures acquired in low- and high-frequency assessment. RESULTS: Adherence was excellent for mood and cognitive assessments (95% and 96%, respectively), did not deteriorate over time, and was not influenced by depression symptom severity or cognitive function at study onset. Analyses examining the relationship between high-frequency cognitive and mood assessment and validated measures showed good correspondence. Daily mood assessments correlated moderately with validated depression questionnaires (r=0.45-0.69 for total daily mood score), and daily cognitive assessments correlated moderately with validated cognitive tests sensitive to depression (r=0.37-0.50 for mean n-back). CONCLUSIONS: This study supports the feasibility and validity of high-frequency assessment of cognition and mood using wearable devices over an extended period in patients with major depressive disorder.

Adapting the Goal Attainment Approach for Major Depressive Disorder.

The need for patient-centered care has become a focal point of healthcare improvement initiatives. Shared decision making-in which patients and clinicians communicate about various treatment options and goals and patient input is considered when making treatment decisions-has been associated with improved health and quality of life. A method of treatment evaluation allowing incorporation of patient-specific goals and perspectives is of increasing interest to healthcare providers, payers, and patients. An approach that allows incorporation of shared goal setting is possible via use of an instrument called the Goal Attainment Scale (GAS). This scale provides the structure for measuring progress toward treatment goals set through patient-clinician collaboration. The goal attainment approach has been used as a primary outcomes measure in numerous studies but not in major depressive disorder (MDD). As MDD is a complex, multidimensional disorder affecting each patient differently, the use of GAS methodology is a relevant framework for setting personalized meaningful treatment goals. Initial research into the feasibility of using the GAS in MDD (GAS-D) to measure patient-centric outcomes that may be neglected when more traditional scales are used has been encouraging. The objective of this Commentary is to provide background and rationale for implementation of the GAS-D in clinical practice.Funding Takeda Pharmaceutical Company, Ltd., and Lundbeck LLC.

Patient attitudes toward and goals for MDD treatment: a survey study.

Background/Objectives: Major depressive disorder (MDD) is a highly prevalent disorder, frequently diagnosed and treated in a primary care setting; however, little information is available about the treatment decision-making process between MDD patients and their providers. A shared decision-making and goal attainment approach to establishing and tracking progress toward treatment goals that are meaningful to individual patients is explored in this survey study. In addition, information about patient perspectives on setting treatment goals, medication selection/switching, and engaging patients with their health care professionals was also collected and evaluated. Methods: A 50-question online survey was administered to members of the PatientsLikeMe community who indicated an MDD diagnosis and a switch in antidepressant medications within the past 2 years. Follow-up interviews were also conducted with a small subset of these participants. Results: Of the 200 participants who completed the survey, 42% reported currently having goals for MDD treatment. These goals were typically in the areas of physical health (62.7%), cognitive functioning (60.2%), and social aspects of life (57.8%). A majority of survey participants (61%) believed the goal attainment approach would be helpful to set and evaluate treatment goals. Conclusions: The data provide important insights into patient perspectives on the development of formal treatment plans and goals for MDD. In addition, the data also support the use of a patient-centric approach to shared decision-making by using a goal attainment scale to establish and track progress toward treatment goals that are meaningful to MDD patients in real-world clinical practice. The results of this study can be used to inform best practices in patient-clinician communication when developing an MDD treatment plan and goals.

A phase 2, randomized, placebo-controlled study of the efficacy and safety of TAK-063 in subjects with an acute exacerbation of schizophrenia.

INTRODUCTION: TAK-063 is a potent, selective inhibitor of phosphodiesterase 10A, an enzyme selectively expressed in medium spiny neurons of the striatum. This randomized, parallel-group study evaluated the efficacy and safety of 20-mg daily TAK-063 versus placebo in subjects with acutely exacerbated symptoms of schizophrenia (NCT02477020). METHODS: Adults aged 18 to 65 with diagnosed schizophrenia and psychotic symptoms that exacerbated within 60 days before screening were included. Subjects who discontinued psychotropic medications before screening were randomized 1:1 to 6 weeks of placebo (n = 81) or 20-mg TAK-063 (n = 83). Weekly efficacy visits were conducted during the treatment period, and dose de-escalation was allowed (blinded) to 10-mg TAK-063 for intolerability. RESULTS: The primary endpoint, change from baseline in the Positive and Negative Syndrome Scale total score at week 6, was not achieved (least-squares mean difference vs placebo [standard error] = -5.46 [3.44]; p = 0.115). Secondary endpoints were generally supportive of antipsychotic efficacy. Consistent with previous phase 1 studies, TAK-063 was safe and well tolerated, and most adverse events were mild or moderate in severity and did not result in discontinuation. No deaths occurred, and the incidence of akathisia and dystonia, categories of extrapyramidal syndromes, was more frequent in the TAK-063 group than placebo. CONCLUSIONS: Although the study did not meet the primary endpoint (effect size = 0.308), the effects of TAK-063 on the primary and secondary endpoints may be suggestive of antipsychotic activity. Interpretation of these results is confounded by a relatively high placebo effect and a lack of dose-ranging or active reference.

A Randomized Multiple Dose Pharmacokinetic Study of a Novel PDE10A Inhibitor TAK-063 in Subjects with Stable Schizophrenia and Japanese Subjects and Modeling of Exposure Relationships to Adverse Events.

BACKGROUND: Phosphodiesterase 10A (PDE10A) is selectively expressed in medium spiny neurons of the striatum. TAK-063 is a selective inhibitor of PDE10A in clinical development for the treatment of schizophrenia. OBJECTIVES: Safety, tolerability, and pharmacokinetics (PK) of TAK-063 were evaluated following multiple rising oral doses, and PK/adverse event (AE) models were developed to characterize the relationship between TAK-063 exposure and incidence of specific AEs. METHODS: Healthy Japanese subjects (HJS) aged 20-55 years and subjects with stable schizophrenia (SSS) aged 18-55 years were enrolled and randomized to either TAK-063 or placebo. Study medication was administered as a tablet once daily (at night) with food over a 7-day period. RESULTS: TAK-063 and placebo groups consisted of 62 and 15 subjects, respectively. A majority of subjects (71 of 77) completed the study. AEs were mostly of mild or moderate severity, and no deaths were reported. The most common AE was somnolence. For equivalent doses, the rate of extrapyramidal syndromes (EPS) was higher in SSS than in HJS. PK parameters were comparable between HJS and SSS at equivalent doses. The incidence of somnolence and EPS symptoms increased with exposure, and this was described with the PK/AE model. A maximum tolerated dose was not determined. CONCLUSIONS: Multiple doses of TAK-063 were safe and well tolerated. PK/AE models characterized the incidence of somnolence and EPS with increasing TAK-063 exposure, and simulations suggested that a once-daily dose range of up to 30 mg would be suitable for future studies. CLINICALTRIALS. GOV IDENTIFIER: NCT01879722.

Effects of ramelteon 8 mg on objective sleep latency in adults with chronic insomnia on nights 1 and 2: pooled analysis.

OBJECTIVE: Ramelteon is an MT(1)/MT(2) melatonin receptor agonist indicated for the treatment of insomnia characterized by difficulty with sleep onset. In previous clinical studies, ramelteon reduced latency to persistent sleep (LPS) in subjects with chronic insomnia. The goal of the current analysis was to determine the average reduction in LPS and overall adverse event profile for subjects taking ramelteon 8 mg. RESEARCH DESIGN AND METHODS: This pooled analysis examined four randomized, double-blind, placebo-controlled clinical trials of ramelteon in subjects with chronic insomnia. The analysis included adults (age 18-83 years) with chronic insomnia who took ramelteon 8 mg or placebo. The primary endpoint of each trial was mean LPS, measured by polysomnography (PSG) on nights 1 and 2. Adverse events were collected for all subjects for the duration of each trial. RESULTS: Efficacy data were available for 566 subjects who took ramelteon 8 mg (mean age 46.7 years) and 556 subjects who took placebo (mean age 47.8 years). Mean LPS at baseline was 66.6 min for the placebo group and 66.9 min for the ramelteon group. At nights 1 and 2, mean LPS for the ramelteon 8 mg group (30.2 min) was significantly less than the mean LPS for the placebo group (43.3 min). The least squares mean difference from placebo was -13.1 min (p < 0.001). Headache (8.9% ramelteon 8 mg, 8.8% placebo) and somnolence (3.5% ramelteon 8 mg, 0.7% placebo) were the most common adverse events. CONCLUSIONS: Ramelteon 8 mg, on average, reduced LPS by approximately 13 min more than placebo on nights 1 and 2 of treatment in adults with chronic insomnia. Ramelteon was well tolerated with a low incidence of adverse events. This mean reduction in LPS versus placebo is similar to what has been reported for other classes of insomnia medications. However, these results reflect nights 1 and 2 of treatment and may not be representative of longer treatments.