Treatment-Resistant Depression Cohort in Europe

Study Overview
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Brief Summary
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The purpose of this study is to assess the participants socio-demographics and disease-related characteristics, long-term naturalistic treatment patterns and the clinical, social and economic outcomes of routine clinical practice in the treatment of participants with treatment-resistant depression (TRD) in a variety of European countries.

Detailed Description
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This TRD cohort study will collect critically important data from routine clinical practice in Europe which will further substantiate the understanding of TRD in European clinical practice, with the aim of improving guidance and informing the development of better treatment strategies for this medically important condition. All data recorded in the case report form (CRF) should be documented in participants' medical records, that will be the primary data source of each participant. Participants who meet the diagnostic criteria for Major Depressive Disorder (MDD) and the diagnostic criteria for TRD, and are initiating or planned to initiate a new antidepressive treatment regimen will participate in the study. The end of the entire study will be 6 months after enrollment of the last participant in the study.

Official Title
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Treatment-Resistant Depression Cohort in Europe

Conditions
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Depressive Disorder, Treatment-Resistant

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Meets the diagnostic criteria for single episode or recurrent MDD, without psychotic features, according to either the International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) or the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) Is considered to suffer from a moderate or severe depressive syndrome, as defined by a Montgomery-Asberg Depression Rating Scale (MADRS) total score greater than or equal to (>=) 20 at baseline Meets/has met the TRD criteria, defined as lack of clinically meaningful improvement, as indicated by a Clinical Global Impression-Change (CGI-C) score >= 4 and/or less than or equal to (<=) 25 percent (%) improvement in MADRS total score (lack of tolerability is not an indicator of non-response), with at least 2 different oral antidepressant treatments (of the same class, of a different class, or a combination of antidepressants or antidepressant with adjunctive antipsychotics) in the current episode of depression, prescribed in adequate dosages (as defined in the Massachusetts General Hospital - Antidepressant Treatment Response Questionnaire [MGH ATRQ]) for adequate duration (at least 6 weeks) with adequate treatment adherence assessed by physicians Is initiating a new antidepressive treatment to treat the current depressive episode Must be capable of providing informed consent, based on the opinion of the participating physician Exclusion Criteria: Has a current or prior diagnosis of a psychotic disorder, MDD with psychotic features, bipolar or related disorders, or intellectual disability, according to DSM-5 or ICD-10 Has homicidal ideation/intent or has suicidal ideation with some intent to act, within 1 month prior to enrollment (per the physician's clinical judgment or based on the Columbia-Suicide Severity Rating Scale [C-SSRS] corresponding to a response of Yes on Item 4 [active suicidal ideation with some intent to act, without specific plan] or Item 5 [active suicidal ideation with specific plan and intent]) or a history of suicidal behavior within 1 year prior to enrollment Has a history of moderate or severe substance use disorder or severe alcohol use disorder according to DSM 5 criteria, except for nicotine and caffeine, within 6 months prior to enrollment Has a lifetime history of hallucinogen-related substance use disorder, with ketamine, phencyclidine (PCP), lysergic acid diethylamide (LSD), or 3,4 methylenedioxy-methamphetamine (MDMA) Has participated in or is currently enrolled in any clinical trial or observational study within the current episode Has previously received esketamine at any time

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 74 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Participants With Diagnosis of Depression<br>This study will evaluate participant's socio-demographic, disease-related and treatment-related characteristics along with outcomes in routine clinical practice across the European region. Only data available within clinical practice, through routine therapeutic procedures and diagnostic assessments, will be recorded. Individual participant information will be recorded from participant's medical records or by use of specific questionnaires. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Treatment Resistant Depression (TRD) Participants With Change From Baseline in Socio-demographic Characteristics | Number of TRD participants with change from baseline in socio-demographic characteristics (education, occupational status, living status, economic status, marital status, legal status) will be assessed. | Baseline up to 21 months (end of study) | 
| Treatment Patterns Over Time for TRD Participants | Treatment patterns (pharmacological and/or non-pharmacological) of TRD participants will be assessed over time. | Baseline up to 21 months (end of study) | 
| Percentage of Participants With Disease-Related Characteristics | Percentage of participants with disease-related characteristics for TRD among Major Depressive Disorder (MDD) participants will be assessed. | Up to 21 months | 
| Severity of Symptoms as Measured by Montgomery-Asberg Depression Rating Scale (MADRS) | The MADRS is a clinician-rated scale designed to measure changes in depression severity due to antidepressant treatment.The MADRS consists of 10 items, each of which is scored from 0 (item not present or normal) to 6 (severe or continuous presence of the symptoms) for a total possible score of 60. Higher scores represent a more severe condition. | Up to 21 months | 
| Participant's Clinical Global Impression-Severity (CGI-S) Score | The CGI-S evaluates the severity of psychopathology on a scale of 0 to 7. Considering total clinical experience, a participant is assessed on severity of mental illness at the time of rating according to: 0=not assessed; 1=normal (not at all ill); 2=borderline mentally ill; 3=mildly ill; 4=moderately ill; 5=markedly ill; 6=severely ill; 7=among the most extremely ill participants. The CGI-S permits a global evaluation of the participant's condition at a given time. | Up to 21 months | 
| Participant's Clinical Global Impression-Change Scale (CGI-C) | The CGI-C is a clinician-rated 7 point scale, ranging from 1 (very much improved) to 7 (very much worse). The CGI C scale will be used in this study to assess any improvement or worsening in a participant's condition versus previous assessments. | Up to 21 months | 
| Healthcare Resource Utilization in TRD Participants | Healthcare resources utilized in TRD participants will be estimated. | Up to 21 months | 
| European Quality of Life (EuroQol) 5-Dimension 5-Level Questionnaire | The EQ-5D-5L descriptive system comprises 5 dimensions - mobility, self-care, usual activities, pain/discomfort, and anxiety/depression - each of which is divided into 5 levels of perceived problems (Level 1 indicating no problem, Level 2 indicating slight problems, Level 3 indicating moderate problems, Level 4 indicating severe problems, and Level 5 indicating extreme problems). | Up to 21 months | 
| Quality of Life in Depression Scale (QLDS) | The QLDS is a disease-specific PRO used to document the impact that depression has on a participant's quality of life. The QLDS is a 34-item self-rated questionnaire consisting of dichotomous response questions, with responses being either True/Not True or Yes/No. It is scored binomially (that is, 0 or 1), with high scores on the QLDS indicating a lower quality of life. | Up to 21 months | 
| Work Productivity and Activity Impairment (WPAI) | The WPAI produces 4 types of scores: absenteeism (work time missed), presenteeism (impairment at work/reduced on-the-job effectiveness), work productivity loss (overall work impairment/absenteeism plus presenteeism), and activity impairment. The WPAI outcomes are expressed as impairment percentages, with higher numbers indicating greater impairment and less productivity, that is, worse outcomes. | Up to 21 months | 
| Level of Disability as Sheehan Disability Scale (SDS) | Participant-reported outcome of functional impact and associated disability will be documented by use of the SDS, a 5-item questionnaire. The first 3 items of the SDS document disruption of work/school, social life, and family life/home responsibilities, each using a rating from 0 to 10. The scores for the first 3 items are summed to create a total score of between 0 and 30, a higher score indicative of greater impairment. It also has 1 item on days lost from school or work and 1 item on days when underproductive. | Up to 21 months | 
| Sequence of Treatments in Participants with TRD | Treatment sequences for participants with TRD within routine clinical care in Europe will be assessed. | Up to 21 months | 
| Demographic Characteristics of TRD Participants | Demographic characteristics (such as age and gender) of TRD participants will be assessed at baseline. | Baseline | 
| Suicidality Risk (Ideation and Attempts) as Measured by Columbia-Suicide Severity Rating Scale (C-SSRS) Score | Suicidal ideation or behavior will be measured using C-SSRS score. C-SSRS is a clinician rated assessment of suicidal behavior and/ or intent. Scale consists of 28 items in 4 sections: suicide behavior, actual attempts, suicidal ideation, and intensity of ideation. Suicidal ideation consists of 5 yes/no items: wish to be dead, non-specific active suicidal thoughts, active suicidal ideation with any methods (not plan) without intention to act, active suicidal ideation with some intent to act without specific plan, active suicidal ideation with specific plan and intent. Worsening of suicidal ideation was an increase in severity of suicidal ideation from baseline. | Baseline |