BackgroundCognitive 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. ObjectiveThe 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. MethodsA 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. ResultsParticipants 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). ConclusionsThe 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.

Background: Antidepressants (ADs) are the mainstay of treatment for patients with major depressive disorder (MDD). Insufficient efficacy of ADs and tolerability issues/side effects, such as treatment-emergent sexual dysfunction (TESD), can lead to treatment discontinuation, symptom persistence, and diminished quality of life. Methods: In this cross-sectional, internet-based survey, patients with MDD (aged 18–64 years) treated with ADs were categorized as continuers, switchers, or discontinuers based on their current oral AD use and any prior oral AD use in the last 12 months. The Carelon Research Healthcare Integrated Research Database was used as a sampling frame to identify survey-eligible adult patients. The survey fielding was conducted from May 29–October 1, 2020. Results: Overall, 900 patients completed the survey (554 [62%] continuers, 298 [33%] switchers, and 48 [5%] discontinuers). The 852 patients currently using ADs reported current use of 1178 ADs (mean: 1.4 AD per patient), while the 294 respondents who either switched or discontinued ADs reported using a total of 534 ADs in the past 12 months (mean: 1.8 AD per patient). Provider recommendations, treatment efficacy, and medication side effects played an important role in AD continuation, switching, or discontinuation. Furthermore, 19% of respondents (continuers and switchers) with no history of sexual problems reported sexual problems with use of at least one current or prior AD. Limitations: The discontinuer cohort was small with few respondents; thus, the between-group statistical comparisons were limited. Conclusions: These findings highlight the importance of patient-physician shared decision-making for MDD management, including minimization of side effects.

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.

Introduction Effective treatment of major depressive disorder (MDD) involves addressing both depressive and functional symptoms, increasing patients’ overall sense of well-being and quality of life (QoL). Methods RELIEVE was an international observational, prospective study in patients ≥18 years with a current diagnosis of a major depressive episode (MDE) initiating vortioxetine in routine clinical practice; outcomes for the cohort of participants from the United States are presented here. Functioning was assessed at weeks 12 and 24 versus baseline using the Sheehan Disability Scale (SDS). Secondary effectiveness analyses assessed changes from baseline to weeks 12 and 24 in functioning, depression severity, cognitive symptoms, sexual function, and QoL. Results 244 participants had an average of 8.2 previous MDEs; mean duration of their current MDE at baseline was 93.5 weeks. Vortioxetine was used as second- or later-line treatment for 80.5% of participants. Least-squares mean (SE) SDS total score significantly decreased from baseline by 7.19 (0.52) points at week 12 and 8.19 (0.56) points at week 24 (p < 0.0001 for both). Significant improvements were also reflected across SDS subscores, depression severity, cognitive function, sexual function, and QoL. Healthcare resource utilization and productivity parameters also improved. Adverse events were observed in 21.8% of patients, with nausea being the most common (7.3%). Conclusion This real-world study demonstrated improvements in functioning, depressive symptoms, and cognitive function in patients with MDD treated with vortioxetine in routine clinical practice in the cohort of patients enrolled in the United States. Outcomes were consistent with the efficacy and safety profile of vortioxetine in randomized controlled trials.

Context: Mobile-based apps have potential to assist primary care clinicians and patients in the shared decision-making (SDM) process for the management of major depressive disorder (MDD). Primary Care Path is a program that includes a patient-facing mobile app and an accompanying care team-facing web interface for supporting depression management in primary care. Objective: Evaluate use of Primary Care Path for MDD management in primary care clinical settings and its impact on SDM, treatment, symptoms, and goal setting and attainment. Study Design and Analysis: Practices were randomized to program use (intervention) or usual care (control). Setting: Four primary care clinical practices in the US. Population Studied: Patient participants were aged ≥18, being treated for MDD, and smartphone users. Clinical care team participants were engaged from all study sites. Intervention/Instrument: Intervention was 18-week use of Primary Care Path program. Patient participants completed online surveys at baseline, 6, 12, and 18 weeks. A subset of care team member participants and intervention patient participants completed interviews at study end. Outcome Measures: SDM-9, treatment changes, PHQ-9, and goal setting and attainment. Results: 76 patients (34 intervention; 42 control) were enrolled; majority were female (79%; 76%), White (91%; 95%), non-Hispanic/Latino/a (85%; 100%), and employed (77%; 81%). No significant differences were observed in SDM-9 between intervention and control; however, in interviews, care team and patient participants reported using the program data to assist in the SDM process. More intervention participants initiated antidepressant medication by weeks 12 (P=0.030) and 18 (P=0.040) and switched medications by weeks 6 (P=0.009) and 12 (P=0.040) versus control. Both groups demonstrated significant improvement in PHQ-9 scores over the study (P<0.001), with no difference in change by group. At week 18, intervention patient participants felt more successful than control participants in achieving their personalized treatment goals (P=0.048). Conclusions: Use of this program in the primary care setting may enhance MDD management, leading to earlier medication optimization and helping patients achieve treatment goals that matter most to them. The results of this study will inform development and uptake of technology-based depression management in primary care to improve patient-centered approaches to care.

OBJECTIVES:The relationship between employee wage status and mental health care utilization has not been characterized in large-scale analyses. This study assessed health care utilization and cost patterns for mental health diagnoses according to wage category among employees with health insurance.STUDY DESIGN:This was an observational, retrospective cohort study for the year 2017 among 2,386,844 adult full-time employees (254,851 with mental health disorders; subgroup of 125,247 with depression) enrolled in self-insured plans in the IBM Watson Health MarketScan research database.METHODS:Participants were stratified into annual wage categories: $34,000 or less; more than $34,000 to $45,000; more than $45,000 to $69,000; more than $69,000 to $103,000; and more than $103,000. Health care utilization and costs were analyzed via regression analyses.RESULTS:Prevalence of diagnosed mental health disorders was 10.7% (9.3% in the lowest-wage category); prevalence of depression was 5.2% (4.2% in the lowest-wage category). Severity of mental health, and specifically depression episodes, was greater in lower-wage categories. All-cause utilization of health care services was higher in patients with mental health diagnoses vs the total population. Among patients with mental health diagnoses, specifically depression, utilization was highest in the lowest- vs highest-wage category for hospital admissions, emergency department visits, and prescription drug supply (all P < .0001). All-cause health care costs were higher in the lowest- vs highest-wage category among patients with mental health diagnoses ($11,183 vs $10,519; P < .0001), specifically depression ($12,206 vs $11,272; P < .0001).CONCLUSIONS:Lower mental health condition prevalence and greater use of high-intensity health care resources highlight the need to more effectively identify and manage mental health conditions among lower-wage workers.

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.

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. This study aims to use qualitative research methods for the user-centered design of a digitally enabled MDD care platform, Pathway Platform, intended to enhance patient engagement, MBC, and SDM. 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. 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. 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.

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.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.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.

Abstract Background Relapse is common in major depressive disorder (MDD). In this study, we evaluated the incremental health care burden of relapse in patients with MDD. Methods This real-world retrospective cohort study used administrative medical and pharmacy claims data to identify commercially insured adult patients in the United States diagnosed with MDD who initiated a new antidepressant between January 1, 2012, and September 30, 2017. All-cause health care resource utilization, total costs, and medication adherence were evaluated in two cohorts: patients with and patients without relapse. Relapse was defined as suicide attempts, psychiatric hospitalization, mental health–related emergency department (ED) visit, use of electroconvulsive therapy, or reinitiation of treatment after a gap ≥6 months. Results The study population included 14,186 patients (7093 baseline-matched patients per cohort). The mean follow-up period was 27.5 and 26.0 months for patients with and patients without relapse, respectively. Patients with relapse had significantly higher rates of hospitalization (16.6% vs 8.5%; p < .0001) and ED visits (54.8% vs 34.7%; p < .0001) than patients without relapse. The total costs for patients with relapse were significantly higher ($12,594 vs $10,445; p < .0001). Patients with relapse were also less adherent to antidepressants (mean proportion of days covered, 0.43 vs 0.49; p < .0001). Conclusions Relapse of MDD was associated with increased total costs and health care utilization and lower adherence to antidepressants. Reducing the risk of relapse may result in a reduction of the associated health care burden; however, findings may only be generalizable to patients with commercial insurance.

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

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.

STUDY OBJECTIVESDepression is an important cause of disability in the United States (US). The care experience of major depressive disorder (MDD) is highly variable and has only been documented to a limited degree. This study examines the prevalence incidence and treatment patterns for MDD in the US general population.METHODSIn this longitudinal study 2 interview waves were conducted between 2002 and 2015. The initial wave (W1) was carried out with 12,218 individuals from the general population in 8 US states with participants aged 18 years or older. In the second wave (W2) 10,931 of the initial participants agreed to be interviewed again 3 years later; the analyses were carried out for individuals who participated in both interviews (N=10,931). Diagnosis of MDD was confirmed according to Diagnostic and Statistical Manual of Mental Disorders Fifth Edition (DSM-5) criteria.RESULTSThe 3-year incidence of MDD was 3.4% (95% CI 3.1%-3.7%). The prevalence of MDD was 5.1% (95% CI 4.7%-5.5%) and 4.2% (95% CI 3.8%-4.6%) in W1 and W2, respectively. The percentages of participants who achieved partial and complete remission were 4.4% (95% CI 4.0%-4.8%) and 3.9% (95% CI 3.5%-4.3%) in W1 compared with 7.9% (95% CI 7.4%-8.4%) and 4.4% (95% CI 4.0%-4.8%) in W2, respectively. The prevalence of MDD was 13.4% and 16.5% in W1 and W2, respectively, when including participants with MDD partial and complete remission episodes. 61.9% of participants with an MDD diagnosis in W1 had at least one associated comorbidity. 41.8% of participants with an MDD diagnosis at W1 still reported significant depressive symptoms at W2. 19.9% of participants in partial remission and 5.5% of participants in complete remission in W1 did not achieve remission in W2. 52.2% and 42.9% of participants with MDD were treated with an antidepressant (AD) in W1 and W2, respectively; selective serotonin reuptake inhibitors (SSRIs) were the most commonly prescribed (34.7% in W1 vs 28.3% in W2). ADs were mainly prescribed by primary care physicians (45.7%) followed by psychiatrists (31.4%), neurologists (2.5%), and other specialties (7.9%). The average duration of treatment was 36.9 (SE 2.4) months. More than one-third of AD users in W1 expressed dissatisfaction with their AD treatment which translated into changes in types of antidepressant in W2.CONCLUSIONDepression affects a sizable part of the general population in the US with a prevalence of MDD at 13.4%-16.5%; yet MDD remains largely undertreated as shown by the finding that only about half (52%) of individuals in this study who met the diagnostic criteria for MDD were treated with an antidepressant (SSRI being the most common treatment). In addition, more than a quarter of patients with MDD in this study did not achieve remission after initial treatment underscoring the challenges in successful antidepressant treatment of MDD.FUNDINGTakeda Pharmaceuticals U.S.A. Inc. and Lundbeck LLC.

BACKGROUND:Major depressive disorder (MDD) is predominantly managed in primary care. However, primary care providers (PCPs) may not consistently follow evidence-based treatment algorithms, leading to variable patient management that can impact outcomes. METHODS:We retrospectively analyzed adult patients with MDD seen at Geisinger, an integrated health system. Utilizing electronic health record (EHR) data, we classified patients as having MDD based on International Classification of Disease (ICD)-9/10 codes or a Patient Health Questionnaire (PHQ)-9 score ≥5. Outcomes assessed included time to first visit with a PCP or behavioral health specialist following diagnosis, antidepressant medication switching, persistence, healthcare resource utilization (HRU), and treatment costs. RESULTS:Among the 38,321 patients with MDD managed in primary care in this study, significant delays between diagnosis with antidepressant prescribing and follow-up PCP visits were observed. There was also considerable variation in care following diagnosis. Overall, 34.9% of patients with an ICD-9/10 diagnosis of MDD and 41.3% with a PHQ-9 score ≥15 switched antidepressants. An ICD-9/10 diagnosis, but not moderately severe to severe depression, was associated with higher costs and HRU. More than 75% of patients with MDD discontinued antidepressant medication within 6 months. LIMITATIONS:The study population was comparable with other real-world studies of MDD, but study limitations include its retrospective nature and reliance on the accuracy of EHRs. CONCLUSIONS:Management of patients with MDD in a primary care setting is variable. Addressing these gaps will have important implications for ensuring optimal patient management, which may reduce HRU and treatment medication costs, and improve treatment persistence.

Background The estimated prevalence of comorbid major depressive disorder (. MDD) is 11% in patients with type 2 diabetes (T2D) and 15–20% in those with cardiovascular disease (CVD). Comorbid MDD continues to be a significant source of economic burden to the healthcare system. Methods We assessed the incremental healthcare burden of comorbid MDD in patients with T2D or CVD. This real-world, retrospective, administrative claims study analyzed commercially insured adults with T2D or CVD diagnosed on at least 2 separate claims within 12 months of each other (between January 1, 2011, and September 30, 2018). CVD included congestive heart failure, peripheral vascular disease, coronary heart disease, and cerebrovascular disease. The study compared patients with and without MDD with either T2D or CVD. Study assessments included all-cause healthcare resource utilization (proportion of patients with hospitalization, emergency department [ED] visits, and outpatient visits) and cost. Results Patients were matched by propensity score for demographics and baseline characteristics, resulting in similar baseline characteristics for the respective subcohorts. After matching, 22,892 patients with T2D (11,446 each with and without MDD) and 28,298 patients with CVD (14,149 each with and without MDD) were included. At follow-up, patients with T2D and MDD had significantly higher rates of hospitalization (26.1% vs 17.4%, P < 0.0001) and ED visits (55.3% vs 43.0%, P < 0.0001) than those observed in patients without MDD. The total cost for patients with T2D and MDD at follow-up was significantly higher than for those without MDD ($16,511 vs $11,550, P < 0.0001). Similarly, at follow-up, patients with CVD and MDD had significantly higher rates of hospitalization (45.4% vs 34.1%, P < 0.0001) and ED visits (66.5% vs 55.4%, P < 0.0001) than those observed in patients without MDD. Total cost at follow-up for patients with CVD and MDD was significantly higher than for those without MDD ($25,546 vs $18,041, P < 0.0001). Conclusions Patients with either T2D or CVD and comorbid MDD have higher total all-cause healthcare utilization and cost than similar patients without MDD. Study findings reinforce the need for appropriate management of MDD in patients with these comorbid diseases, which in turn may result in cost reductions for payers. Trial registration Not applicable.

The safety and tolerability of vortioxetine in adults with major depressive disorder was assessed. Tolerability was based on the nature, incidence and severity of treatment-emergent adverse events (TEAEs) during acute (6/8) week treatment in 11 randomized, double-blind placebo-controlled short-term studies in major depressive disorder: six with an active reference. Symptoms following discontinuation were assessed through the Discontinuation-Emergent Signs and Symptoms checklist in three studies. Long-term (⩽52 weeks) tolerability was evaluated in five open-label extension studies. Patients (n =5701) were acutely treated with either placebo (n=1817), vortioxetine (5–20mg/day; n=3018), venlafaxine XR (225mg/day; n=113) or duloxetine (60mg/day; n=753). The withdrawal rate due to TEAEs during treatment with vortioxetine (5–20mg/day) was 4.5–7.8%, compared with placebo (3.6%), venlafaxine XR (14.2%) or duloxetine (8.8%). Common TEAEs (incidence ⩾5% and >2 × placebo) with vortioxetine (5–20mg/day) were nausea (20.9–31.2%) and vomiting (2.9–6.5%). For vortioxetine (5–20mg/day), the incidence of TEAEs associated with insomnia was 2.0–5.1% versus 4.0% for placebo, and with sexual dysfunction 1.6–1.8% versus 1.0% for placebo. Discontinuation symptoms as assessed by the mean Discontinuation-Emergent Signs and Symptoms total score after abrupt discontinuation were comparable to placebo in the first and second week. Vortioxetine had no effect relative to placebo on clinical laboratory parameters, body weight, heart rate or blood pressure. Vortioxetine showed no clinically relevant effect on ECG parameters, including the QTcF interval. In long-term treatment, no new types of TEAEs were seen; the mean weight gain was 0.7–0.8kg. Thus, vortioxetine (5–20mg/day) appears safe and generally well tolerated in the treatment of major depressive disorder.

Vortioxetine is approved for the treatment of adults with major depressive disorder. This open-label extension (OLE) study evaluated the safety and tolerability of vortioxetine in the long-term treatment of major depressive disorder patients, as well as evaluated its effectiveness using measures of depression, anxiety, and overall functioning. This was a 52-week, flexible-dose, OLE study in patients who completed one of three randomized, double-blind, placebo-controlled, 8-week vortioxetine trials. All patients were switched to 10mg/day vortioxetine for week 1, then adjusted between 15 and 20mg for the remainder of the study, but not downtitrated below 15mg. Safety and tolerability were assessed on the basis of treatment-emergent adverse events (TEAEs), vital signs, laboratory values, physical examination, and the Columbia-Suicide Severity Rating Scale. Efficacy measures included the Montgomery-angstrom sberg Depression Rating Scale, the Hamilton Anxiety Scale, the Clinical Global Impression Scale-Severity of Illness, and the Sheehan Disability Scale. Of the 1075 patients enrolled, 1073 received at least one dose of vortioxetine and 538 (50.0%) completed the study. A total of 537 patients withdrew early, with 115 (10.7% of the original study population) withdrawing because of TEAEs. Long-term treatment with vortioxetine was well tolerated; the most common TEAEs (10%) were nausea and headache. Laboratory values, vital signs, and physical examinations revealed no trends of clinical concern. The mean Montgomery-angstrom sberg Depression Rating Scale total score was 19.9 at the start of the extension study and 9.0 after 52 weeks of treatment (observed cases). Similar improvements were observed with the Hamilton Anxiety Scale (-4.2), the Clinical Global Impression Scale-Severity of Illness (-1.2), and the Sheehan Disability Scale (-4.7) total scores after 52 weeks of treatment (observed case). In this 52-week, flexible-dose OLE study, 15 and 20mg vortioxetine were safe and well tolerated. After entry into this study, patients continued to show improvement in depression and anxiety symptoms, as well as overall functioning, throughout the treatment period.