Clinical trial NCT03701724: Cost-utility Analysis of Maintenance rTMS for Treatment-resistant Depression
Official title: Cost-utility Analysis of Maintenance rTMS for Treatment-resistant Depression
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Treatment-resistant Depression
Keywords: Major Depressive Disorder
Unipolar depression
Chronic depression
Recurrent depression
Depressive disorder
Magnetic stimulation
Non-invasive brain stimulation
1 Hertz (Hz) rTMS
Maintenance rTMS
Cost-utility
Efficiency
Medico-economic
Antidepressants
Lead sponsor: Nantes University Hospital
Sponsor class: OTHER
First posted: 2018-10-10
Enrollment: 119
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

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.

Eligibility criteria: 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)

Primary outcomes:
measure: Cost-utility ratio, according to collective perspective of rTMS use in TRD compared to conventional therapeutic approaches without active rTMS.
timeFrame: 12 months
Secondary outcomes:
measure: Cost-utility ratio, according to collective perspective of rTMS use in TRD compared to conventional therapeutic approaches without active rTMS.
timeFrame: 24 months
measure: Budget impact analysis of spreading the most efficient strategy for using rTMS (systematic mTMS or rTMS course in case of relapse).
timeFrame: 5 years
measure: Major depressive disorder history
timeFrame: Baseline
measure: Level of depression treatment-resistance
timeFrame: Baseline
measure: professional status
timeFrame: Baseline,12 months and 24 months
measure: marital status
timeFrame: Baseline,12 months and 24 months
measure: Response rate
timeFrame: 12 months and 24 months
measure: Remission rate
timeFrame: 12 months and 24 months
measure: Relapse-free survival
timeFrame: 12 months and 24 months
measure: MADRS score
timeFrame: Baseline, 2 months, 6 months , 9 months, 12 months, 18 months, 24 months
measure: Beck Depression Inventory (BDI) score
timeFrame: Baseline, 2 months, 6 months , 9 months, 12 months, 18 months, 24 months
measure: Clinical Global Impression (CGI) score
timeFrame: Baseline, 2 months, 6 months , 9 months, 12 months, 18 months, 24 months
measure: Adverse events linked to the medical treatment for depression
timeFrame: 24 months
measure: Declarative drug compliance via the MARS (Medication Adherence Report Scale)
timeFrame: baseline, 12 months and 24 months
measure: Declarative drug compliance via the CRS (Clinician Rating Scale)
timeFrame: baseline, 12 months and 24 months
measure: Treatment(s) switch(es)
timeFrame: Baseline, 2 months, 6 months , 9 months, 12 months, 18 months, 24 months
measure: Treatment(s) dose increase
timeFrame: Baseline, 2 months, 6 months , 9 months, 12 months, 18 months, 24 months
measure: Treatments combination(s)
timeFrame: Baseline, 2 months, 6 months , 9 months, 12 months, 18 months, 24 months
measure: Rate of suicide attempts and suicides
timeFrame: 12 months and 24 months
measure: Patient's quality of life
timeFrame: baseline,12 months and 24 months
measure: Response rate at the end of rTMS courses
timeFrame: 1 month after each rTMS treatments
measure: Remission rate at the end of rTMS courses
timeFrame: 1 month after each rTMS treatments
measure: Number of days between the successive rTMS courses
timeFrame: 24 months
measure: Total number of rTMS sessions
timeFrame: 24 months
measure: Time between relapses
timeFrame: 24 months
measure: Compliance with rTMS
timeFrame: 24 months
measure: Patient acceptability of the rTMS technique: Analog Visual Scale
timeFrame: 24 months
Other outcomes:
Locations:
city: Angers
country: France
facility: CHU d'Angers
city: Besançon
country: France
facility: CHRU de Besançon
city: Bron
country: France
facility: CH le Vinatier Lyon
city: Caen
country: France
facility: CHU de Caen
city: Clermont-Ferrand
country: France
facility: CHU de Clermont-Ferrand
city: Dijon
country: France
facility: CHU de Dijon
city: Esvre-sur-Indre
country: France
facility: Clinique de Vontes
city: Lille
country: France
facility: EPSM de Lille
city: Limoges
country: France
facility: CH Esquirol - Limoges
city: Montpellier
country: France
facility: CHU de Montpellier
city: Nantes
country: France
facility: Nantes University Hospital
city: Neuilly-sur-Marne
country: France
facility: EPS de Ville-Evrard
city: Paris
country: France
facility: GH PItié Salpétrière
city: Paris
country: France
facility: GHU Psychiatrie Ste Anne
city: Poitiers
country: France
facility: CH Henri Laborit (Poitiers)
city: Rennes
country: France
facility: Centre hospitalier Guillaume Regnier Rennes
city: Rouen
country: France
facility: CH du Rouvray - Rouen
city: Toulouse
country: France
facility: CHU de Toulouse
city: Tours
country: France
facility: CHU de Tours / CHRU de Tours
Study officials:
affiliation: Nantes University Hospital
name: Samuel Bulteau, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Bulteau S, Laurin A, Volteau C, Dert C, Lagalice L, Schirr-Bonnans S, Bukowski N, Guitteny M, Simons L, Cabelguen C, Pichot A, Tessier F, Bonnin A, Lepage A; ACOUSTIM Investigators Group; HUGOPSY Network; Vanelle JM, Sauvaget A, Riche VP. Cost-utility analysis of curative and maintenance repetitive transcranial magnetic stimulation (rTMS) for treatment-resistant unipolar depression: a randomized controlled trial protocol. Trials. 2020 Apr 5;21(1):312. doi: 10.1186/s13063-020-04255-9.