Burden Of Major Depressive Disorder Research Articles

Clinical and sociodemographic features of the Texas resilience against depression (T-RAD) study: Findings from the initial cohort

ObjectiveThe burden of major depressive disorder is compounded by a limited understanding of its risk factors, the limited efficacy of treatments, and the lack of precision approaches to guide treatment selection. The Texas Resilience Against Depression (T-RAD) study was designed to explore the etiology of depression by collecting comprehensive socio-demographic, clinical, behavioral, neurophysiological/neuroimaging, and biological data from depressed individuals (D2K) and youth at risk for depression (RAD). MethodsThis report details the baseline sociodemographic, clinical, and functional features from the initial cohort (D2K N = 1040, RAD N = 365). ResultsOf the total T-RAD sample, n = 1078 (76.73 %) attended ≥2 in-person visits, and n = 845 (60.14 %) attended ≥4 in-person visits. Most D2K (84.82 %) had a primary diagnosis of any depressive disorder, with a bipolar disorder diagnosis being prevalent (13.49 %). RAD participants (75.89 %) did not have a psychiatric diagnosis, but other non-depressive diagnoses were present. D2K participants had 9-item Patient Health Questionnaire scores at or near the moderate range (10.58 ± 6.42 > 24 yrs.; 9.73 ± 6.12 10–24 yrs). RAD participants were in the non-depressed range (2.19 ± 2.65). While the age ranges in D2K and RAD differ, the potential to conduct analyses that compare at-risk and depressed youth is a strength of the study. The opportunity to examine the trajectory of depressive symptoms in the D2K cohort over the lifespan is unique. LimitationsAs a longitudinal study, missing data were common. ConclusionT-RAD will allow data to be collected from multiple modalities on a clinically well-characterized sample. These data will drive important discoveries on diagnosis, treatment, and prevention of depression.

Global, regional, and national temporal trend in burden of major depressive disorder from 1990 to 2019: An analysis of the global burden of disease study

Major depressive disorder (MDD) is one of the leading causes of disability worldwide. Comprehensive description of the global burden of MDD and its attributable risk factors is essential for policymaking but currently lacking. In this study, we aim to estimate the burden of MDD in terms of incidence, prevalence, and years lived with disability (YLDs), along with its attributable risk factors at global, regional, and rational level between 1990 and 2019, using data from the Global Burden of Diseases, Injuries, and Risk Factors Study 2019. Data analysis was completed on July 1, 2023. In 2019, 274.80 million (95 % uncertainty interval [UI], 241.28 to 312.77) new cases of MDD were identified globally, with an increase of 59 % from 1990. A total of 37.20 million (25.65 to 51.22) YLDs were attributable to MDD, accounting for the largest proportion of mental disorder YLDs (29.7 %). Countries in the low sociodemographic index quantile exhibited the highest age-standardized incidence rate of MDD, with Uganda (7836.2, per 100,000 person-years, 6713.7 to 9181.1) and Palestine (7687.7, 6546.1 to 9023.9) reporting the highest rates among them. The United States had the highest increase in age-standardized rates, with an average annual percent change of 0.99. Females had 1.6 times higher age-standardised rates than males, ranging from 1.2 (Oceania) to 2.2 (tropical Latin America) times across 21 regions. Globally, the proportions of YLDs due to MDD attributable to bullying victimization, childhood sexual abuse, and intimate partner violence were 4.86 %, 5.46 %, and 8.43 % in 2019, respectively. The heavy burden of MDD serves as a stark reminder that a coordinated response from governments and health communities is urgently needed to scale up mental health services and implement effective interventions, particularly in low-income countries.

The long-term spatio-temporal trends in burden and attributable risk factors of major depressive disorder at global, regional and national levels during 1990-2019: a systematic analysis for GBD 2019.

Caused by multiple risk factors, heavy burden of major depressive disorder (MDD) poses serious challenges to public health worldwide over the past 30 years. Yet the burden and attributable risk factors of MDD were not systematically known. We aimed to reveal the long-term spatio-temporal trends in the burden and attributable risk factors of MDD at global, regional and national levels during 1990-2019. We obtained MDD and attributable risk factors data from Global Burden of Disease Study 2019. We used joinpoint regression model to assess the temporal trend in MDD burden, and age-period-cohort model to measure the effects of age, period and birth cohort on MDD incidence rate. We utilized population attributable fractions (PAFs) to estimate the specific proportions of MDD burden attributed to given risk factors. During 1990-2019, the global number of MDD incident cases, prevalent cases and disability-adjusted life years (DALYs) increased by 59.10%, 59.57% and 58.57%, respectively. Whereas the global age-standardized incidence rate (ASIR), age-standardized prevalence rate (ASPR) and age-standardized DALYs rate (ASDR) of MDD decreased during 1990-2019. The ASIR, ASPR and ASDR in women were 1.62, 1.62 and 1.60 times as that in men in 2019, respectively. The highest age-specific incidence, prevalence and DALYs rate occurred at the age of 60-64 in women, and at the age of 75-84 in men, but the maximum increasing trends in these age-specific rates occurred at the age of 5-9. Population living during 2000-2004 had higher risk of MDD. MDD burden varied by socio-demographic index (SDI), regions and nations. In 2019, low-SDI region, Central sub-Saharan Africa and Uganda had the highest ASIR, ASPR and ASDR. The global PAFs of intimate partner violence (IPV), childhood sexual abuse (CSA) and bullying victimization (BV) were 8.43%, 5.46% and 4.86% in 2019, respectively. Over the past 30 years, the global ASIR, ASPR and ASDR of MDD had decreased trends, while the burden of MDD was still serious, and multiple disparities in MDD burden remarkably existed. Women, elderly and populations living during 2000-2004 and in low-SDI regions, had more severe burden of MDD. Children were more susceptible to MDD. Up to 18.75% of global MDD burden would be eliminated through early preventing against IPV, CSA and BV. Tailored strategies-and-measures in different regions and demographic groups based on findings in this studywould be urgently needed to eliminate the impacts of modifiable risk factors on MDD, and then mitigate the burden of MDD.

EPH239 Incremental Cost Burden of Major Depressive Disorder in Patients with Rheumatoid Arthritis in Korea

EPH239 Incremental Cost Burden of Major Depressive Disorder in Patients with Rheumatoid Arthritis in Korea

The burden of major depressive disorder in the Middle East and North Africa region, 1990-2019.

Major depressive disorder (MDD) is one of the leading causes of disability. We aimed to report the MDD-attributable prevalence, incidence and years lived with disability (YLDs) in the Middle East and North Africa (MENA) region from 1990 to 2019 by age, sex and socio-demographic index (SDI). Publicly available data on the burden of MDD were retrieved from the Global Burden of Disease (GBD) study 2019 for the 21 countries in MENA. The counts and age-standardised rates (per 100,000) were presented, along with their corresponding 95% uncertainty intervals. In 2019, MDD had an age-standardised point prevalence of 3322.1 and an incidence rate of 4921.7 per 100,000 population in MENA. Furthermore, there were 4.1 million YLDs in 2019. However, there were no substantial changes in the MDD burden over the period 1990-2019. In 2019, Palestine had the highest burden of MDD. The highest prevalence, incidence and YLDs attributable to MDD were found in the 35-39 age group. In 2019, the YLD rate in MENA was higher than the global rate for almost all age groups. Furthermore, there was a broadly negative association between the YLD rate and SDI. The study highlights the need to prevent the disorder using a multidisciplinary approach and for the provision of cost-effective treatments for those affected, in order to increase their quality of life.

EE480 Economic Burden of Major Depressive Disorder in the United States in 2019-2020: A Societal Perspective

To provide a comprehensive evaluation of the economic burden of major depressive disorder (MDD) in the United States (US) in 2019 and estimate the early impact that the COVID-19 pandemic in 2020 may have had on the overall disease burden.

EE249 Healthcare Resource Utilization with Adjunctive Cariprazine and Other Atypical Antipsychotics in Patients with Major Depressive Disorder

Patients with major depressive disorder (MDD) often experience inadequate response to antidepressant monotherapy, which contributes to the considerable burden of MDD. Treatment with adjunctive atypical antipsychotics (AA) is a guideline-recommended treatment strategy in patients with inadequate response, yet little is known about healthcare resource utilization (HRU) associated with different AAs. This study evaluated HRU in patients with MDD treated adjunctively with cariprazine versus other AAs.

Sequence Modeling of Passive Sensing Data for Treatment Response Prediction in Major Depressive Disorder.

Major depressive disorder (MDD) is a prevalent mental health condition and has become a pressing societal challenge. Early prediction of treatment response may aid in the rehabilitation engineering of depression, which is of great practical significance for the relief of suffering and burden of MDD. In this paper, we present a sequence modeling approach that uses data collected by passive sensing techniques to predict patients with an outcome of treatment responded defined by the reduction in clinical administrated scales. Hundreds of patients with MDD have been recruited from outpatient clinics at 4 psychiatric sites. Each has been delivered with a self-developed app to passively record their daily phone usage and physical data with minimal human action. An unavoidable dilemma in passive sensing is missing values. To overcome that, the proposed approach combined feature extraction and sequence modeling methods to fully utilize the pattern of missing values from longitudinal data. With no treatment constraints, it enables us to predict the treatment response of MDD 8-10 weeks before the completion of the treatment course, leaving time for preventative measures. Our work explored the feasibility of treatment response prediction using longitudinal passive sensing data and sparse ground truth, and also has the potential for preventing depression by forecasting treatment outcomes weeks in advance.

Study protocol of DIVERGE, the first genetic epidemiological study of major depressive disorder in Pakistan.

Globally, 80% of the burdenof major depressive disorder (MDD) pertains to low- and middle-income countries. Research into genetic and environmental risk factors has the potential to uncover disease mechanisms that may contribute to better diagnosis and treatment of mental illness, yet has so far been largely limited to participants with European ancestry from high-income countries. The DIVERGE study was established to help overcome this gap and investigate genetic and environmental risk factors for MDD in Pakistan. DIVERGE aims to enrol 9000 cases and 4000 controls in hospitals across the country. Here, we provide the rationale for DIVERGE, describe the study protocol and characterise the sample using data from the first 500cases. Exploratory data analysis is performed to describe demographics, socioeconomic status, environmental risk factors, family history of mental illness and psychopathology. Many participants had severe depression with 74% of patients who experienced multiple depressive episodes. It was a common practice to seek help for mental health struggles from faith healers and religious leaders. Socioeconomic variables reflected the local context with a large proportion of women not having access to any education and the majority of participants reporting no savings. DIVERGE is a carefully designed case-control study of MDD in Pakistan that captures diverse risk factors. As the largest genetic study in Pakistan, DIVERGE helps address the severe underrepresentation of people from South Asian countries in genetic as well as psychiatric research.

Annual costs among patients with major depressive disorder and the impact of key clinical events.

BACKGROUND: The economic burden of major depressive disorder (MDD) is substantial and increasing; however, the impact of key clinical events (eg, hospitalization, suicide attempt/ideation, and treatment changes) on health care resource use and costs are less established. OBJECTIVE: To evaluate the health care utilization and costs among patients with MDD, particularly for those with key clinical events. METHODS: In this retrospective analysis, administrative health care claims from the IBM MarketScan Commercial Claims and Encounters Database were used to identify adults with a new diagnosis of MDD (January 1, 2009, to December 31, 2017). Patients with 12 months or more of continuous health care coverage before and after the initial medical claim with an MDD diagnosis (index date) and 1 or more pharmacy claims for an antidepressant within 60 days of any qualifying medical claim were included. The effect of post-index date key clinical events (eg, treatment changes, moderate to severe MDD, MDD-related emergency department [ED] visits, MDD-related hospitalizations, suicide attempt/ideation, severe mental health disorder, use of brain stimulation therapies) on all-cause total costs was assessed. Actual allcause costs were summarized descriptively and reported per patient per year (PPPY). Multivariable analyses compared differences in all-cause costs during follow-up, depending on whether patients experienced a key clinical event. RESULTS: A total of 455,082 patients met eligibility criteria. The average age was 41 years and 64% of patients were female. Mean (SD) all-cause PPPY costs during the follow-up period were $10,074 ($25,694). The most common key clinical events were treatment changes, moderate to severe MDD diagnosis, and MDD-related ED visits. The majority of patients (90.1%) experienced at least 1 treatment change, which was most commonly treatment discontinuation. Generally, mean costs for up to 90 days following an event were higher than those preceding the event. In multivariable analyses, patients with any key clinical events had 51% higher PPPY allcause health care costs compared with those who did not have any key clinical events. Compared with patients without key clinical events, follow-up costs were more than 2 times higher among patients with severe mental health disorder, MDD-related hospitalization, and suicide attempt/ideation. The most impactful key clinical event was treatment with electroconvulsive therapy, vagal nerve stimulation, or transcranial magnetic stimulation, in which patients incurred 4.3 times higher follow-up costs than those who did not receive one of these treatments. CONCLUSIONS: Key clinical events exacerbate health care resource use and costs among patients with MDD. Effective therapeutic regimens initiated optimally in the course of treatment may mitigate costly clinical events associated with MDD. DISCLOSURES: This study was sponsored by Allergan plc (prior to its acquisition by AbbVie). The sponsor was involved in the study design, data collection, data analysis, manuscript preparation, and publication decisions. All authors met the ICMJE authorship criteria. Neither honoraria nor payments were made for authorship. Dr Cutler is a consultant for AbbVie, Acadia Pharmaceuticals, Akili Interactive, Alfasigma, Alkermes, Allergan (now AbbVie), Avanir, BioXcel Therapeutics, BlackThorn Therapeutics, Intra-Cellular Therapies, Ironshore, Janssen, Karuna Therapeutics, Lundbeck, Neurocrine Biosciences, Noven, Otsuka, Sage Therapeutics, Sunovion, Supernus Pharmaceuticals, Takeda, Teva and Tris Pharma; has received speaker/promotional honoraria from AbbVie, Acadia Pharmaceuticals, Alfasigma, Alkermes, Allergan, Avanir, Intra-Cellular Therapies, Ironshore, Janssen, Lundbeck, Neurocrine Biosciences, Noven, Otsuka, Sunovion, Takeda, Teva, and Tris Pharma; and has received research grants from Aevi Genomics, Akili Interactive, Alkermes, Allergan (now AbbVie), Arbor Pharmaceuticals, Biohaven, Ironshore, KemPharm, Lilly, Lundbeck, Neos Therapeutics, Novartis, Otsuka, Purdue Canada, Sunovion, Supernus Pharmaceuticals, Takeda and Tris Pharma. Drs Keyloun and Gillard are AbbVie employees and may hold stock. Dr Higa was an employee of AbbVie at the time of the study and may hold stock. Ms Park is an employee of Merative, formerly IBM Watson Health, which received funding from Allergan (prior to its acquisition by AbbVie) to conduct this analysis. Dr Bonafede was an employee of IBM Watson Health, now Merative, which received funding from Allergan (prior to its acquisition by AbbVie) to conduct this analysis. Dr Jain has served as a consultant to Addrenex, Allergan (now AbbVie), Avanir, Janssen, Lilly, Lundbeck, Merck, Neos Therapeutics, Neurocrine Biosciences, Otsuka, Pamlab, Pfizer, Shionogi, Shire, Sunovion, Supernus, Takeda, and Teva; has been a paid speaker for Addrenex, Alkermes, Allergan (now AbbVie), Lilly, Lundbeck, Merck, Neos Therapeutics, Otsuka, Pamlab, Pfizer, Rhodes, Shionogi, Shire, Sunovion, Takeda, and Tris Pharmaceuticals; has received research support from Allergan (now AbbVie), AstraZeneca, Lilly, Lundbeck, Otsuka, Pfizer, Shire, and Takeda; and has served on the advisory boards for Addrenex, Alkermes, Avanir, Forum, Janssen, Lilly, Lundbeck, Merck, Neos Therapeutics, Neurocrine Biosciences, Otsuka, Pamlab, Pfizer, Shionogi, Shire, Sunovion, Supernus, Takeda, and Teva.

Economic burden of major depressive disorder: a case study in Southern Iran

BackgroundDepression disorders are a leading cause of disability in the world which imposes a significant economic burden on patients and societies The present study aimed to determine the economic burden of Major Depressive Disorder (MDD) on the patients referred to the reference psychiatric single-specialty hospitals in southern Iran in 2020.MethodsThis cross-sectional research is a partial economic evaluation and a cost-of-illness study conducted in southern Iran in 2020. A total of 563 patients were enrolled through the census method, and a researcher-made data collection form was used to gather the required information. The prevalence-based and the bottom-up approaches were also used to collect the cost information and calculate the costs, respectively. The data on direct medical, direct non-medical, and indirect costs were obtained using the information in the patients’ medical records and insurance bills as well as their self-reports or those of their companions. To calculate the indirect costs, the human capital approach was used as well.ResultsThe results showed that the annual cost of MDD was $ 2717.41 Purchasing Power Parity (PPP) (USD 2026.13) per patient in 2020. Direct medical costs accounted for the largest share of the costs (73.68%), of which hoteling and regular beds expenses were the highest (57.70% of the total direct medical costs). The shares of direct non-medical and indirect costs were 7.52 and 18.80%, respectively, and the economic burden of the disease in the country was estimated at $7,120,456,596 PPP (USD 5,309,088,699).ConclusionIn general, due to the high prevalence of MDD and the chronicity of the disease, the costs of its treatment can impose a heavy economic burden on the society, healthcare system, insurance system, and the patients themselves. Therefore, it is suggested that health policymakers and managers should take appropriate measures to increase the basic and supplemental insurance coverage of these patients. In addition, in order to reduce the costs, proper and equitable distribution of psychiatrists and psychiatric beds, expansion of home care services, and use of Internet-based technologies and the cyberspace to follow up the treatment of these patients are recommended.

Clinical and economic burden of major depressive disorder with acute suicidal ideation or behavior in a US Veterans Health Affairs database

Objective Although a high incidence of major depressive disorder (MDD) and an increased risk of suicide are observed among the veteran population, there are yet limited real-world data characterizing patients with MDD with acute suicidal ideation/behavior (MDSI) in the Veterans Health Administration (VHA) system. We assessed the clinical and economic burden, including comorbidities, treatment patterns, health care resource utilization, and health care costs, among veterans and their family members with MDSI within the VHA system. Methods This retrospective, longitudinal analysis of VHA datasets (10/1/2015–3/31/2018) evaluated the clinical and economic burden associated with MDSI and compared this population with matched MDD alone (ie, MDD diagnosis without acute suicidal ideation/behavior) and non-MDD (ie, neither MDD nor acute suicidal ideation/behavior) cohorts. Results Among 11,203 patients with MDSI, the proportions of patients who filled a prescription for ≥1 antidepressant during the 12-month pre- and 6-month post-periods were significantly higher compared with patients with MDD alone (53.7% vs 28.8%; P <0.05, and 72.3% vs 44.1%; P <0.05, respectively). During the 12-month pre-period, the MDSI cohort had the highest proportion of patients with ≥1 mental health–related inpatient visit compared with the MDD alone and non-MDD cohorts (13.2% vs 2.3% vs 1.4%, respectively; P <0.05), and the highest mental health–related costs per patient ($8,853 vs $1913 vs $1079, respectively). For the 6-month post-period, the MDSI cohort had the highest proportion of patients with ≥1 mental health–related inpatient visit compared with the MDD alone and non-MDD cohorts (60.4% vs 7.9% vs 0.8%, respectively; P <0.05), and had the highest mental health–related costs per patient ($20,334 vs $4803 vs $545, respectively). Conclusions Findings demonstrate significant clinical and economic burden for those in the VHA system diagnosed with MDSI and highlight unmet needs and opportunities for improving the care of this vulnerable group.

Sex Difference in Global Burden of Major Depressive Disorder: Findings From the Global Burden of Disease Study 2019.

ObjectivesGlobally, major depressive disorder (MDD) is considered to be a leading cause of disability. In this article, we aim to investigate the sex difference in global burden of MDD by year, age, and socioeconomic development, utilizing disability-adjusted life-years (DALYs).MethodsGlobal and national sex-specific DALY estimates caused by MDD from 1990 to 2019 and in different age groups were obtained from the Global Burden of Disease (GBD) Study 2019. Human development index (HDI) was used as an indicator of national socioeconomic development. Spearman correlation and linear regression analyses were performed to explore the relationship between national socioeconomic development and sex difference in MDD burden.ResultsSex difference in global burden of MDD persisted between 1990 and 2019, with age-standardized DALY rates being 352 among males vs. 593 among females in 1990 and 354 vs. 564 in 2019. Females had higher burden of MDD than males at the same age. Disability-adjusted life-years numbers and rates among both sexes rapidly increased with age for those aged 10–24 years, along with gradually enlarging sex difference. Age-standardized DALY rates among females were higher than that among males for each HDI-based country group (P < 0.001). National age-standardized DALY rates among both sexes were negatively related to HDI. However, female-to-male age-standardized DALY rate ratios were positively associated with HDI (Spearman r = 0.383, P < 0.001; standardized β = 0.300, P < 0.001).ConclusionAlthough some improvement in sex difference in global burden of MDD has been achieved, it still persists in the past three decades, with females bearing more burden than males. To reduce sex difference in global MDD burden, more attention should be paid to young people and people in developed countries. The findings highlight the importance of making sex-specific health policy to manage mental impairment caused by MDD.

Treating Insomnia with High Risk of Depression Using Therapist-Guided Digital Cognitive, Behavioral, and Circadian Rhythm Support Interventions to Prevent Worsening of Depressive Symptoms: A Randomized Controlled Trial

Introduction: The global disease burden of major depressive disorder urgently requires prevention in high-risk individuals, such as recently discovered insomnia subtypes. Previous studies targeting insomnia with fully automated eHealth interventions to prevent depression are inconclusive: dropout was high and likely biased, and depressive symptoms in untreated participants on average improved rather than worsened. Objective: This randomized controlled trial aimed to efficiently prevent the worsening of depressive symptoms by selecting insomnia subtypes at high risk of depression for internet-based circadian rhythm support (CRS), cognitive behavioral therapy for insomnia (CBT-I), or their combination (CBT-I+CRS), with online therapist guidance to promote adherence. Methods: Participants with an insomnia disorder subtype conveying an increased risk of depression (n = 132) were randomized to no treatment (NT), CRS, CBT-I, or CBT-I+CRS. The Inventory of Depressive Symptomatology – Self Report (IDS-SR) was self-administered at baseline and at four follow-ups spanning 1 year. Results: Without treatment, depressive symptoms indeed worsened (d = 0.28, p = 0.041) in high-risk insomnia, but not in a reference group with low-risk insomnia. Therapist-guided CBT-I and CBT-I+CRS reduced IDS-SR ratings across all follow-up assessments (respectively, d = –0.80, p = 0.001; d = –0.95, p < 0.001). Only CBT-I+CRS reduced the 1-year incidence of clinically meaningful worsening (p = 0.002). Dropout during therapist-guided interventions was very low (8%) compared to previous automated interventions (57–62%). Conclusions: The findings tentatively suggest that the efficiency of population-wide preventive strategies could benefit from the possibility to select insomnia subtypes at high risk of developing depression for therapist-guided digital CBT-I+CRS. This treatment may provide effective long-term prevention of worsening of depressive symptoms. Trial registration: the Netherlands Trial Register (NL7359).

Global prevalence and burden of depressive and anxiety disorders in 204 countries and territories in 2020 due to the COVID-19 pandemic

SummaryBackgroundBefore 2020, mental disorders were leading causes of the global health-related burden, with depressive and anxiety disorders being leading contributors to this burden. The emergence of the COVID-19 pandemic has created an environment where many determinants of poor mental health are exacerbated. The need for up-to-date information on the mental health impacts of COVID-19 in a way that informs health system responses is imperative. In this study, we aimed to quantify the impact of the COVID-19 pandemic on the prevalence and burden of major depressive disorder and anxiety disorders globally in 2020.MethodsWe conducted a systematic review of data reporting the prevalence of major depressive disorder and anxiety disorders during the COVID-19 pandemic and published between Jan 1, 2020, and Jan 29, 2021. We searched PubMed, Google Scholar, preprint servers, grey literature sources, and consulted experts. Eligible studies reported prevalence of depressive or anxiety disorders that were representative of the general population during the COVID-19 pandemic and had a pre-pandemic baseline. We used the assembled data in a meta-regression to estimate change in the prevalence of major depressive disorder and anxiety disorders between pre-pandemic and mid-pandemic (using periods as defined by each study) via COVID-19 impact indicators (human mobility, daily SARS-CoV-2 infection rate, and daily excess mortality rate). We then used this model to estimate the change from pre-pandemic prevalence (estimated using Disease Modelling Meta-Regression version 2.1 [known as DisMod-MR 2.1]) by age, sex, and location. We used final prevalence estimates and disability weights to estimate years lived with disability and disability-adjusted life-years (DALYs) for major depressive disorder and anxiety disorders.FindingsWe identified 5683 unique data sources, of which 48 met inclusion criteria (46 studies met criteria for major depressive disorder and 27 for anxiety disorders). Two COVID-19 impact indicators, specifically daily SARS-CoV-2 infection rates and reductions in human mobility, were associated with increased prevalence of major depressive disorder (regression coefficient [B] 0·9 [95% uncertainty interval 0·1 to 1·8; p=0·029] for human mobility, 18·1 [7·9 to 28·3; p=0·0005] for daily SARS-CoV-2 infection) and anxiety disorders (0·9 [0·1 to 1·7; p=0·022] and 13·8 [10·7 to 17·0; p<0·0001]. Females were affected more by the pandemic than males (B 0·1 [0·1 to 0·2; p=0·0001] for major depressive disorder, 0·1 [0·1 to 0·2; p=0·0001] for anxiety disorders) and younger age groups were more affected than older age groups (−0·007 [–0·009 to −0·006; p=0·0001] for major depressive disorder, −0·003 [–0·005 to −0·002; p=0·0001] for anxiety disorders). We estimated that the locations hit hardest by the pandemic in 2020, as measured with decreased human mobility and daily SARS-CoV-2 infection rate, had the greatest increases in prevalence of major depressive disorder and anxiety disorders. We estimated an additional 53·2 million (44·8 to 62·9) cases of major depressive disorder globally (an increase of 27·6% [25·1 to 30·3]) due to the COVID-19 pandemic, such that the total prevalence was 3152·9 cases (2722·5 to 3654·5) per 100 000 population. We also estimated an additional 76·2 million (64·3 to 90·6) cases of anxiety disorders globally (an increase of 25·6% [23·2 to 28·0]), such that the total prevalence was 4802·4 cases (4108·2 to 5588·6) per 100 000 population. Altogether, major depressive disorder caused 49·4 million (33·6 to 68·7) DALYs and anxiety disorders caused 44·5 million (30·2 to 62·5) DALYs globally in 2020.InterpretationThis pandemic has created an increased urgency to strengthen mental health systems in most countries. Mitigation strategies could incorporate ways to promote mental wellbeing and target determinants of poor mental health and interventions to treat those with a mental disorder. Taking no action to address the burden of major depressive disorder and anxiety disorders should not be an option.FundingQueensland Health, National Health and Medical Research Council, and the Bill and Melinda Gates Foundation.

Added burden of major depressive disorder on cardiovascular morbidity and mortality among patients with cardiovascular disease and the modifying effects of antidepressants: A national retrospective cohort study

Background: To evaluate the likelihood of a future cardiovascular event (i.e., in-hospital mortality or cardiovascular disease [CVD] complications/interventions) among patients with CVD and major depressive disorder (MDD) compared to those without MDD, and the antidepressant use on future cardiovascular events between the two groups. MethodsThis is a retrospective cohort with propensity score matching with 8941 patients with CVD and MDD, and 8941 non-MDD patients using data from the Longitudinal Health Insurance Database from 1999 to 2013 in Taiwan. The outcome was in-hospital mortality and the incidence of revascularization (i.e., percutaneous transluminal coronary angioplasty [PTCA] and coronary artery bypass graft surgery [CABG]). Results: Patients with CVD and MDD were more likely to need revascularization (an adjusted hazard ratio [aHR]: 1.26 and 95% CI: 1.12-1.43) than those without MDD, regardless of whether PTCA (aHR: 1.23 and 95% CI: 1.07-1.40) or CABG (aHR: 1.60 and 95% CI: 1.16-2.21) had occurred. Antidepressant use was associated with a tendency of reduced risk of mortality (aHR: 0.92 and 95% CI: 0.84-1.00). Although the magnitude of aHR ranged from 0.92 to 0.95 with revascularization, they did not reach significant levels. LimitationsSome covariates could not be controlled because they were not included in the national register dataset, and the causality is limited in an observational study. ConclusionsPatients with CVD with MDD are more likely to experience a cardiovascular complication requiring intervention than CVD patients without MDD. Antidepressant use is associated with reduced in-hospital mortality.

PMH9 Economic Burden of Major Depressive Disorder with Acute Suicidal Ideation or Behavior in the United States

This study assessed healthcare resource utilization (HRU) and costs of patients with major depressive disorder (MDD) and acute suicidal ideation or behavior (MDSI) compared to MDD without suicidal ideation (MDD) and without MDD (non-MDD). Adults were identified in the MarketScan® Databases (10/2015-02/2020). The MDSI cohort received an MDD diagnosis on the same day or within 6 months before a claim for acute suicidal ideation or behavior (index date). Index date was a random date with an MDD claim in the MDD cohort, and a random date in the non-MDD cohort. All patients had continuous eligibility ≥12 months pre- and ≥1 month post-index. HRU and costs (2020 US$) were compared during 1- and 12-month post-index periods between the MDSI and control cohorts matched 1:1. The MDSI cohort included 73,242 patients (mean age 35 years, 60.6% female, 37.2% Medicaid coverage) matched to controls in each cohort. During 1 month post-index, the MDSI cohort had 12.8 times more inpatient admissions and 3.3 times more emergency room (ER) visits versus the MDD cohort, as well as 67.2 times more inpatient admissions, 8.9 times more ER visits, and 2.9 times more outpatient visits versus the non-MDD cohort (all p<0.001). During 12 months post-index, HRU remained higher in the MDSI versus control cohorts. During 1 and 12 months post-index, respectively, the MDSI cohort had higher mean healthcare costs per-patient-month ($7,272 and $2,068) vs the MDD ($2,017 and $1,122) and non-MDD ($598 and $696) cohorts (all p<0.001). During 1 and 12 months post-index, inpatient costs drove 89.5% and 77.8% of cost differences versus the MDD cohort, and 81.1% and 63.6% versus the non-MDD cohort, respectively. MDSI is associated with substantial economic burden driven by inpatient costs. The economic burden of MDSI is concentrated in the first month post-index, persisting during the following year.

Hallucinogenic/psychedelic 5HT2A receptor agonists as rapid antidepressant therapeutics: Evidence and mechanisms of action.

Major depressive disorder (MDD) is among the most prevalent mental health disorders worldwide, and it is associated with a reduced quality of life and enormous costs to health care systems. Available drug treatments show low-to-moderate response in most patients, with almost a third of patients being non-responders (treatment-resistant). Furthermore, most currently available medications need several weeks to achieve therapeutic effects, and the long-term use of these drugs is often associated with significant unwanted side effects and resultant reductions in treatment compliance. Therefore, more effective, safer, and faster-acting antidepressants with enduring effects are needed. Together with ketamine, psychedelics (or classic or serotoninergic hallucinogens) such as lysergic acid diethylamide (LSD), psilocybin, and ayahuasca are among the few compounds with recent human evidence of fast-acting antidepressant effects. Several studies in the 1950s to 1970s reported antidepressive and anxiolytic effects of these drugs, which are being confirmed by modern trials (LSD, one trial; psilocybin, five trials; ayahuasca, two trials). The effects of these drugs appear to be produced primarily by their agonism at serotonin (5-hydroxytryptamine, 5-HT) receptors, especially the 5-HT2A receptor. Considering the overall burden of MDD and the necessity of new therapeutic options, the promising (but currently limited) evidence of safety and efficacy of psychedelics has encouraged the scientific community to explore more fully their beneficial effects in MDD.

Identification of Crucial Genes and Diagnostic Value Analysis in Major Depressive Disorder Using Bioinformatics Analysis.

Despite the prevalence and burden of major depressive disorder (MDD), our current understanding of the pathophysiology is still incomplete. Therefore, this paper aims to explore genes and evaluate their diagnostic ability in the pathogenesis of MDD. Firstly, the expression profiles of mRNA and microRNA were downloaded from the gene expression database and analyzed by the GEO2R online tool to identify differentially expressed genes (DEGs) and differentially expressed microRNAs (DEMs). Then, the DAVID tool was used for functional enrichment analysis. Secondly, the comprehensive protein-protein interaction (PPI) network was analyzed using Cytoscape, and the network MCODE was applied to explore hub genes. Thirdly, the receiver operating characteristic (ROC) curve of the core gene was drawn to evaluate clinical diagnostic ability. Finally, mirecords was used to predict the target genes of DEMs. A total of 154 genes were identified as DEGs, and 14 microRNAs were identified as DEMs. Pathway enrichment analysis showed that DEGs were mainly involved in hematopoietic cell lineage, PI3K-Akt signaling pathway, cytokine-cytokine receptor interaction, chemokine signaling pathway, and JAK-STAT signaling pathway. Three important modules are identified and selected by the MCODE clustering algorithm. The top 12 hub genes, including CXCL16, CXCL1, GNB5, GNB4, OPRL1, SSTR2, IL7R, MYB, CSF1R, GSTM1, GSTM2, and GSTP1, were identified as important genes for subsequent analysis. Among these important hub genes, GSTM2, GNB4, GSTP1 and CXCL1 have the good diagnostic ability. Finally, by combining these four genes, the diagnostic ability of MDD can be improved to 0.905, which is of great significance for the clinical diagnosis of MDD. Our results indicate that GSTM2, GNB4, GSTP1 and CXCL1 have potential diagnostic markers and are of great significance in clinical research and diagnostic application of MDD. This result needs a large sample study to further confirm the pathogenesis of MDD.

PMH11 Quantifying the Real-World Economic Burden of Major Depressive Disorder and Treatment-Resistant Depression in England: National and Regional Estimates

Treatment-Resistant Depression (TRD) refers to a subtype of Major Depressive Disorder (MDD), an episodic psychiatric illness, in which patients have not responded to at least two successive antidepressant treatments in a single episode. This research assessed healthcare resource utilisation (HCRU) and direct healthcare costs associated with MDD and TRD in England, of which limited data currently exist, particularly by geographic region. Adult patients (aged 18yrs+) were indexed on first antidepressant prescription, requiring MDD diagnosis (Read/ICD-10 code) within 90 days, from Jan 2011-May 2015 using linked primary, secondary and specialist mental healthcare data in England from the Clinical Practice Research Datalink (Protocol: 19_019R). Failure of 2+ adequate oral antidepressant regimens within the index episode (i.e. substitution, addition or augmentation of antidepressant treatments) constituted TRD. HCRU/cost outcomes (primary care, medication, outpatient, inpatient) were assessed from indexing by treatment resistance and region. 40,686 patients with MDD were included (mean age 43yrs, 62% female); 1,301 (3%) were classified as TRD during follow-up (median follow-up: TRD 40mths, non-treatment-resistant MDD 28mths). Mean total healthcare costs per-patient [per-patient per-month] of £2,650 [£113] observed for non-treatment-resistant MDD (range: East Midlands £1,101 [£76], South East Coast £3,065 [£119]) and £4,715 [£121] observed for TRD (range: East Midlands £2,170 [£79], North East £5,784 [£166]). Total costs were primarily driven by inpatient stays (non-treatment-resistant MDD: £1,368 [£61] vs. TRD: £2,259 [£59]) and primary care visits (non-treatment-resistant MDD: £786 [£32] vs. TRD: £1,431 [£37]), with similar regional trends. Total direct healthcare costs were numerically higher for TRD compared with non-treatment-resistant MDD, with substantial geographical variations. Inpatient stays and primary care visits accounted for ≈80% of all costs; outpatient costs were negligible in comparison. Further research in a larger sample of patients with TRD is warranted to fully understand regional differences observed, and to explore reasons for these differences.