Cost-utility Analysis of Maintenance rTMS for Treatment-resistant Depression

Not Applicable

Active, not recruiting

• Conditions: Treatment-resistant Depression
• Interventions: Device: rTMS course in case of relapse; Device: Systematic maintenance rTMS; Device: sham rTMS

• Registration Number: NCT03701724
• Lead Sponsor: Nantes University Hospital

Brief Summary

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.

Detailed Description

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 Timeline

• Study First Submitted: 2018-09-17
• Study First Submitted QC: 2018-10-09
• Study First Posted: 2018-10-10
• Study Start: 2018-11-05
• Status Verified: 2022-09
• Last Update Submitted: 2022-09-15
• Last Update Posted: 2022-09-16
• Primary Completion: 2022-12-15
• Study Completion: 2023-12-30

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 119

Inclusion Criteria

• Major depressive disorder according to Diagnostic and Statistical Manual of Mental Disorders (DSM) 5 MADRS >19
• Episode duration: 12 weeks to 3 years.
• 2 to 4 unsuccessful treatment lines (including antidepressants, and potentialization agents lithium and quetiapine) despite adequate dosage and duration (6 weeks stable posology)
• Ability to consent and express informed consent, to answer questionnaires and to go to follow-up visits.
• Affiliation to social security

Exclusion Criteria

• Bipolar disorder
• Schizophrenia and other psychotic disorders
• Mental retardation or developmental disorder
• Substance abuse or dependence
• Depression symptoms better explained by medical conditions
• Neurologic conditions (e.g.,previous epilepsy or unexplained seizures, stroke, trauma, infection, metabolic disease, severe migraines, multiple sclerosis, brain tumor)
• Presence of at least one contra-indication to rTMS
• Pregnancy/breast-feeding
• Patient who previously received 5 lines or more pharmacological treatment for the current episode (excluding symptomatic psychotropic drugs, e.g. benzodiazepines and hypnotics)
• Former use of electroconvulsive therapy or rTMS within the current episode.
• Previous failure of adequate ECT (at least 12 well conducted sessions) or rTMS course (at least 20 well conducted sessions) in the medical history.
• History of at least two courses of ECT, previous need for maintenance ECT.
• Protection measure : maintenance of justice, tutelage, legal guardianship
• Woman of childbearing age without effective contraception
• Liberty deprivation (e.g. incarceration, therapeutic injunction)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
rTMS course in case of relapse (arm B)	rTMS course in case of relapse	Active rTMS treatment followed, for responders, by additional rTMS courses, in case of relapse Depression usual medical treatment (psychosocial approach and/or pharmacotherapy and/or, ECT...)
Systematic maintenance rTMS (arm A)	Systematic maintenance rTMS	Active rTMS treatment followed, for responders, by systematic maintenance rTMS Depression usual medical treatment (psychosocial approach and/or pharmacotherapy and/or, ECT...)
Sham rTMS (arm C)	sham rTMS	sham rTMS followed, for responders, by either systematic sham mTMS (50%) or additional sham rTMS course in case of relapse(50%) Depression usual medical treatment (psychosocial approach and/or pharmacotherapy and/or, ECT...)

Primary Outcome Measures

Name	Time	Method
Cost-utility ratio, according to collective perspective of rTMS use in TRD compared to conventional therapeutic approaches without active rTMS.	12 months	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.

Secondary Outcome Measures

Name	Time	Method
marital status	Baseline,12 months and 24 months	patient's marital status (married, widow, single...)
Level of depression treatment-resistance	Baseline	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.
Cost-utility ratio, according to collective perspective of rTMS use in TRD compared to conventional therapeutic approaches without active rTMS.	24 months	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
Relapse-free survival	12 months and 24 months	Number of patients with no relapse. Relapse is defined as follows: MADRS ≥ 20 (see detailed description of MADRS in outcome 8)
professional status	Baseline,12 months and 24 months	patient's professional status (active, unemployed, retired...)
Remission rate	12 months and 24 months	Remission is defined as follows: MADRS score ≤ 10 (see detailed description of MADRS in outcome 8)
MADRS score	Baseline, 2 months, 6 months , 9 months, 12 months, 18 months, 24 months	MADRS score (see detailed description of MADRS in outcome 8)
Clinical Global Impression (CGI) score	Baseline, 2 months, 6 months , 9 months, 12 months, 18 months, 24 months	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.
Budget impact analysis of spreading the most efficient strategy for using rTMS (systematic mTMS or rTMS course in case of relapse).	5 years	Comparison of intervention costs on the study sample and projection of these costs over 5 years, from the health insurance and hospital perspectives
Major depressive disorder history	Baseline	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.
Response rate	12 months and 24 months	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.
Beck Depression Inventory (BDI) score	Baseline, 2 months, 6 months , 9 months, 12 months, 18 months, 24 months	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).
Treatment(s) dose increase	Baseline, 2 months, 6 months , 9 months, 12 months, 18 months, 24 months	Number of drug(s) dose(s) increases prescribed to the patient
Treatments combination(s)	Baseline, 2 months, 6 months , 9 months, 12 months, 18 months, 24 months	List of drugs (name) prescribed to the patient
Adverse events linked to the medical treatment for depression	24 months	Number and types of adverse events linked to the medical treatment for depression
Number of days between the successive rTMS courses	24 months	Number of days between end of rTMS course X and beginning of course X+1, for each patient
Patient acceptability of the rTMS technique: Analog Visual Scale	24 months	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"
Declarative drug compliance via the CRS (Clinician Rating Scale)	baseline, 12 months and 24 months	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.
Treatment(s) switch(es)	Baseline, 2 months, 6 months , 9 months, 12 months, 18 months, 24 months	Number of treatment switches per patient
Response rate at the end of rTMS courses	1 month after each rTMS treatments	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)
Total number of rTMS sessions	24 months	total number of rTMS sessions per patient
Time between relapses	24 months	Number of days between relapses, per patient
Declarative drug compliance via the MARS (Medication Adherence Report Scale)	baseline, 12 months and 24 months	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
Rate of suicide attempts and suicides	12 months and 24 months	number of suicide attempts and suicides per patient
Patient's quality of life	baseline,12 months and 24 months	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
Remission rate at the end of rTMS courses	1 month after each rTMS treatments	Remission is defined as follows: MADRS score ≤ 10 (see detailed description of MADRS in outcome 8)
Compliance with rTMS	24 months	number of missed sessions over the number of planned sessions, per patient

Trial Locations

Locations (19)

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

CH Esquirol - Limoges; 🇫🇷 Limoges, France

EPSM de Lille; 🇫🇷 Lille, France

CHU de Montpellier; 🇫🇷 Montpellier, France

Nantes University Hospital; 🇫🇷 Nantes, France

GH PItié Salpétrière; 🇫🇷 Paris, France

EPS de Ville-Evrard; 🇫🇷 Neuilly-sur-Marne, France

Centre hospitalier Guillaume Regnier Rennes; 🇫🇷 Rennes, France

CHU de Tours / CHRU de Tours; 🇫🇷 Tours, France

CHU de Toulouse; 🇫🇷 Toulouse, France

CH Henri Laborit (Poitiers); 🇫🇷 Poitiers, France

GHU Psychiatrie Ste Anne; 🇫🇷 Paris, France

CH du Rouvray - Rouen; 🇫🇷 Rouen, France