Treatment resistant depression (TRD) is a frequent, debilitating condition mostly treated by antidepressants. Repeated magnetic transcranial stimulation (rTMS) has proven adjuvant efficacy in TRD in the acute phase of treatment with a very good tolerance and acceptability. Maintenance rTMS (mTMS) is a strategy consisting in adding regular single TMS sessions after response to an acute course in order to keep the benefit of initial treatment over several month or years. Demonstrating that rTMS is efficient to improve long-term prognosis and decrease economic burden would have a tremendous impact in clinical practice in psychiatry. Thus the investigator's aim is to analyze the long term impact of mTMS treatment on costs, but also quality of life and clinical issues.
TRD is associated with enormous social, economic, and personal costs. In literature, psychosocial and pharmacological interventions showed limited one year long-term efficacy in terms of relapse (only 10% of sustained remission at one-year follow-up actually) and quality of life due to refractoriness, observance and adverse effects. In the recent years the field of non-invasive brain stimulation became more mature with an increasing level of evidence reaching Level 1 for rTMS as curative treatment for depression in international guidelines. It is a safe and well tolerated treatment but with still high relapse rate at 6 month and one year (comparable to those former described for ECT). mTMS is a promising tool (as it was proven for ECT) to achieve sustained response several month after treatment in a significant proportion of patients. Little is known about its long-term economic and social benefit which is a crucial question given its time consuming nature. To date there is no large Randomized Clinical Trial (RCT) assessing the long-term health economic interest or adjuvant mTMS compared to treatment as usual (TAU) alone in unipolar TRD . This study is a double-blind randomized controlled trial aiming at determining a 12 month cost-utility analysis, according to collective perspective, of two different modalities of rTMS (systematic mTMS or curative rTMS in case of relapse) for TRD compared to TAU alone. The secondary aims are to describe 24 month cost-utility, longitudinal clinical issues in terms of mood and quality of life, prognosis factors, as well as TAU actual strategies in that population.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
OTHER
Masking
TRIPLE
Enrollment
119
Same parameters as the initial course (session of 8,5 minutes, at 1 Hz, on the right dorsolateral prefrontal cortex (DLPFC) targeting with either neuronavigation or the Beam). The frequency is : 2 sessions / week during 1 month, then 1 session / week during 2 months and finally 1 session every 2 weeks during 8 months.
Same parameters as the initial course. The frequency is the same as the initial course: one daily session on 5 consecutive working days from Monday to Friday for at least 20 to 30 sessions over 4 to 6 weeks.
The sham stimulation consists of the identical rTMS procedure at the identical location using a commercial figure-eight sham coil. However, it does not produce the identical tactile sensation. A local electrical stimulation will be delivered with two disposable Electromyogram (EMG) electrodes using a transcutaneous electrical nerve stimulation (TENS) Stimulator.
CHU d'Angers
Angers, France
CHRU de Besançon
Besançon, France
CH le Vinatier Lyon
Bron, France
CHU de Caen
Caen, France
CHU de Clermont-Ferrand
Clermont-Ferrand, France
CHU de Dijon
Dijon, France
Clinique de Vontes
Esvre-sur-Indre, France
EPSM de Lille
Lille, France
CH Esquirol - Limoges
Limoges, France
CHU de Montpellier
Montpellier, France
...and 9 more locations
Cost-utility ratio, according to collective perspective of rTMS use in TRD compared to conventional therapeutic approaches without active rTMS.
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, 3 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.
Time frame: 12 months
Cost-utility ratio, according to collective perspective of rTMS use in TRD compared to conventional therapeutic approaches without active rTMS.
Quality Adjusted Life Year (QALYs) as estimated from responses to the Euroqol-5 Dimensions (EQ-5D) health-related quality of life questionnaire The costs will be measured by the additional of the following costs: Drugs dispensing via Health insurance database SNIIRAM, hospitalizations, work stoppages and care consumption collected in a declarative patient questionnaire
Time frame: 24 months
Budget impact analysis of spreading the most efficient strategy for using rTMS (systematic mTMS or rTMS course in case of relapse).
Comparison of intervention costs on the study sample and projection of these costs over 5 years, from the health insurance and hospital perspectives
Time frame: 5 years
Major depressive disorder history
This outcome will be assessed by patient interview, with the following data (not exhaustive): date of initial symptoms, length of the current episode, family antecedents of mood disorders.
Time frame: Baseline
Level of depression treatment-resistance
Maudsley Staging model score: a multidimensional tool to quantify treatment resistance in depression. It evaluates 5 dimensions: 1) length of the current depressive episode, 2) symptomatic intensity, 3) failure of the antidepressant drugs, 4) Increase treatment 5) use of Electro-convulsive therapy. The total score ranges from 3 to 15. 15 being the highest level of treatment resistance.
Time frame: Baseline
professional status
patient's professional status (active, unemployed, retired...)
Time frame: Baseline,12 months and 24 months
marital status
patient's marital status (married, widow, single...)
Time frame: Baseline,12 months and 24 months
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.
Time frame: 12 months and 24 months
Remission rate
Remission is defined as follows: MADRS score ≤ 10 (see detailed description of MADRS in outcome 8)
Time frame: 12 months and 24 months
Relapse-free survival
Number of patients with no relapse. Relapse is defined as follows: MADRS ≥ 20 (see detailed description of MADRS in outcome 8)
Time frame: 12 months and 24 months
MADRS score
MADRS score (see detailed description of MADRS in outcome 8)
Time frame: Baseline, 2 months, 6 months , 9 months, 12 months, 18 months, 24 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).
Time frame: Baseline, 2 months, 6 months , 9 months, 12 months, 18 months, 24 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.
Time frame: Baseline, 2 months, 6 months , 9 months, 12 months, 18 months, 24 months
Adverse events linked to the medical treatment for depression
Number and types of adverse events linked to the medical treatment for depression
Time frame: 24 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
Time frame: baseline, 12 months and 24 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.
Time frame: baseline, 12 months and 24 months
Treatment(s) switch(es)
Number of treatment switches per patient
Time frame: Baseline, 2 months, 6 months , 9 months, 12 months, 18 months, 24 months
Treatment(s) dose increase
Number of drug(s) dose(s) increases prescribed to the patient
Time frame: Baseline, 2 months, 6 months , 9 months, 12 months, 18 months, 24 months
Treatments combination(s)
List of drugs (name) prescribed to the patient
Time frame: Baseline, 2 months, 6 months , 9 months, 12 months, 18 months, 24 months
Rate of suicide attempts and suicides
number of suicide attempts and suicides per patient
Time frame: 12 months and 24 months
Patient's quality of life
Short-Form 36 (SF 36) questionnaire: instrument used to assess multidimensional health-related quality of life, which measures 8 health related parameters: physical function, social function, physical role, emotional role, mental health, energy, pain, general health perceptions
Time frame: baseline,12 months and 24 months
Response rate at the end of rTMS courses
Response is defined as follows: decrease of the MADRS score by at least 50% compared to baseline score (see detailed description of MADRS in outcome 8)
Time frame: 1 month after each rTMS treatments
Remission rate at the end of rTMS courses
Remission is defined as follows: MADRS score ≤ 10 (see detailed description of MADRS in outcome 8)
Time frame: 1 month after each rTMS treatments
Number of days between the successive rTMS courses
Number of days between end of rTMS course X and beginning of course X+1, for each patient
Time frame: 24 months
Total number of rTMS sessions
total number of rTMS sessions per patient
Time frame: 24 months
Time between relapses
Number of days between relapses, per patient
Time frame: 24 months
Compliance with rTMS
number of missed sessions over the number of planned sessions, per patient
Time frame: 24 months
Patient acceptability of the rTMS technique: Analog Visual Scale
Analog Visual Scale of acceptability of the rTMS completed by the patient, ranging from 0 to 10. 0 being "not acceptable" and 10 being "totally acceptable"
Time frame: 24 months
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