Transcranial Direct Current Stimulation (tDCS) Cost-utility-analysis in Medical Care on Depressive Episode With One Drug Therapy Failure.

Study Overview
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Brief Summary
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The purpose of this study is to determine the transcranial direct current stimulation (tDCS) cost-utility in the depression therapy. This is a 3 years medico-economics study with 1 year follow-up period involving patients with 1 or 2 depression treatment(s) failed. Eligible subject will be randomized in 2 groups, usual care with tDCS cure (arm A) or only usual care (arm B).

Detailed Description
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Transcranial direct current stimulation is a non-invasive brain neuromodulation technique. tDCS can be a new therapy in depression. This study focuses on tDCS cost-utility-analysis. Each patient is following during 12 months. Patients are randomized in 2 arms. Arm A usual care with tDCS cure or arm B usual care without tDCS. Patient in arm A get a initial tDCS cure one week after randomization. If these patients are answering to the treatment, they can have a new cure in case of relapse. This new cure can start from the second month following initial treatment.

Official Title
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Transcranial Direct Current Stimulation (tDCS) Cost-utility-analysis in Medical Care on Depressive Episode With One Drug Therapy Failure.

Conditions
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Depression

Intervention / Treatment
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* Other: tDCS associated with usual care
* Other: Usual care


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Depression according to Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-V) with 1 or 2 failed antidepressant treatments for the current episode. MADRS score superior or equal to 15. Patient agreeing to participate in the study Patient able to answer questionnaires and able to go at research center for follow-up visit. Patient with social insurance Exclusion Criteria: Electroconvulsive therapy or repetitive transcranial magnetic stimulation for current depressive episode. Depressive episode with psychotic symptoms or mixed. Schizophrenia or addiction to another substance than nicotine Severe neurological disorder (like epilepsy, neurological affect, neurological disease) Severe and / or progressive somatic pathology (leave to the investigator judgment) preventing from participation in the study. tDCS specific contraindications (intracerebral metallic implant, pacemaker) Pregnancy or breast feeding. Woman of childbearing age without contraception (hormonal or with medical device). Participation in another interventional clinical trial legal protection Persons incarcerated or in obligation of treatment / medical treatment order.

Ages Eligible for Study
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Minimum Age: 18 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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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Usual care and tDCS (Arm A)<br>Arm A patient receives a first tDCS treatment in association with usual care (medication, psychotherapy...). If the patient is responding to tDCS, he can have other tDCS treatments in case of relapse. | Other: tDCS associated with usual care<br>* A tDCS cure will be given to the group tDCS, one week after their randomization. This will be done in association with usual care: medication and psychotherapy Parameters: Anodal stimulation on dorso-lateral prefrontal cortex left, 2mA current. Treatment will consist of 15 days with 30 minutes stimulation per day, 5 days a week for 3 weeks.<br>|
| Active Comparator: Usual care without tDCS (Arm B)<br>Arm B patient receives usual care: medication management and psychotherapy. | Other: Usual care<br>* Medication and psychotherapy as prescribed in usual care<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cost-utility ratio, according to collective perspective of tDCS use in depression compared to usual care without active tDCS. | The utility will be measured by : Quality Adjusted Life Year (QALYs) as estimated from responses to the Euroqol-5 Dimensions (EQ-5D) health-related quality of life questionnaire. The questionnaire focuses on 5 dimensions: mobility, personal autonomy, current activities, pain/discomfort and anxiety/depression. For each of these dimensions, 5 answers are possible. The costs will be measured by the addition of the following costs: Drugs dispensing via Health insurance database National system of information of the French health insurance (SNIIRAM), hospitalizations, work stoppages and care consumption collected in a declarative patient questionnaire. | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Budget impact analysis of spreading the most efficient strategy for using tDCS | Comparison of intervention costs on the study sample and projection of these costs over 5 years, from the health insurance and hospital perspectives | 5 years | 
| Response rate | Response is defined as follows: decrease of the MADRS score by at least 50% compared to baseline score. MADRS stands for Montgomery-Asberg Depression Rating Scale. It is used to measure the severity of depressive episodes in patients with mood disorders. The questionnaire includes questions on the following symptoms 1. Apparent sadness 2. Reported sadness 3. Inner tension 4. Reduced sleep 5. Reduced appetite 6. Concentration difficulties 7. Lassitude 8. Inability to feel 9. Pessimistic thoughts 10. Suicidal thoughts and each item yields a score of 0 to 6. The overall score ranges from 0 to 60. A score from 0 to 6 being normal/symptom absent and a score >34 being severe depression. | at baseline, at the end of each tDCS cure (for Arm A patients) through study completion (12 months) and at 12 months for all patients | 
| Remission rate | Remission rate is defined as follows: MADRS score < 10 (see detailed description of MADRS in outcome 3) | 12 months | 
| Relapse-free survival | Number of patients with no relapse. Relapse is defined as follows: MADRS ≥ 20 (see detailed description of MADRS in outcome 3) | 12 months | 
| MADRS score | MADRS score (see detailed description of MADRS in outcome 3) | At Baseline, one month, 2 months, 6 months and 12 months. | 
| Beck Depression Inventory (BDI) score | The BDI is 13-item multiple-choice self-report inventory, for measuring the severity of depression. The global score is an addition of each item's score and ranges from 0 (minimal depression) to 39 (severe depression). | At Baseline, one month, 2 months, 6 months and 12 months. | 
| Clinical Global Impression (CGI) score | The Clinical Global Impression (CGI) rating scales are measures of symptom severity, treatment response and the efficacy of treatments in treatment studies of patients with mental disorders. Each scale is rated from 0 to 7. 0 being the best level and 7 the worst level. | At Baseline, one month, 2 months, 6 months and 12 months. | 
| MOCA Score (Montreal Cognitive Assessment) | Thirty items assessing multiple cognitive domains are contained in the MoCA: short-term memory (5 points); visuospatial abilities via clock drawing (3 points), and a cube copy task (1 point); executive functioning via an adaptation of Trail Making Test Part B (1 point), phonemic fluency (1 point), and verbal abstraction (2 points); attention, concentration, and working memory via target detection (1 point), serial subtraction (3 points), digits forward (1 point), and digits backward (1 point); language via confrontation naming with low-familiarity animals (3 points), and repetition of complex sentences (2 points); and orientation to time and place (6 points) | At Baseline, one month, 2 months, 6 months and 12 months. | 
| Adverse events linked to the medical treatment for depression | Number and types of adverse events linked to the medical treatment for depression | 12 months | 
| Rate of suicide attempts | number of suicide attempts per patient | 12 months | 
| Rate of suicides | number of suicides | 12 months | 
| Treatment(s) switch(es) | Number of treatment switches per patient | At Baseline, one month, 2 months, 6 months and 12 months. | 
| Treatment(s) dose increase | Number of drug(s) dose(s) increases prescribed to the patient | At Baseline, one month, 2 months, 6 months and 12 months. | 
| Treatments combination(s) | List of drugs (name) prescribed to the patient | at Baseline, one month, 2 months, 6 months and 12 months. | 
| Declarative drug compliance via the MARS (Medication Adherence Report Scale) | MARS is the Medication Adherence Report Scale, including 10 questions, the global score ranges from 0 to 10, 0 corresponds to the worst drug compliance and 10 to an excellent drug compliance | at baseline and at 12 months | 
| Declarative drug compliance via the CRS (Clinician Rating Scale) | CRS is the Clinician Rating Scale , including 7 questions, the global score ranges from 1 to 7, 7 being the worst level of drug compliance. | at baseline and at 12 months | 
| Total number of tDCS sessions | total number of tDCS sessions per patient | 12 months | 
| Number of days between the successive tDCS cures | Number of days between end of tDCS cure X and beginning of cure X+1, for each patient | 12 months | 
| Adverse events linked to tDCS | Number and types of adverse events linked to the tDCS | 12 months | 
| Compliance with tDCS | number of missed sessions over the number of planned sessions, per patient | 12 months | 
| Patient acceptability of the tDCS technique: Analog Visual Scale | Analog Visual Scale of acceptability of the tDCS completed by the patient, ranging from 0 to 10. 0 being not acceptable and 10 being totally acceptable | at the end of the first tDCS cure (up to one month) | 
| professional status | patient's professional status (active, unemployed, retired...) | At baseline | 
| Impact of the implementation of the tDCS on the organization of care | The organizational impact of the tDCS will be evaluated from the point of view of doctors, nurse and patients: staff, equipment, maintenance, location and mobilization time of these resources, using a specific questionnaire | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Depression, psychiatry, health economics, Neurostimulation, tDCS