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

NCT ID: NCT03701724

Last Updated: 2022-09-16

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: NA
• Total Enrollment: 119 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-11-05
• Study Completion Date: 2023-12-30

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.

Conditions

Treatment-resistant Depression

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: OTHER
• Blinding Strategy: TRIPLE

Study Groups

Systematic maintenance rTMS (arm A)

Active rTMS treatment followed, for responders, by systematic maintenance rTMS Depression usual medical treatment (psychosocial approach and/or pharmacotherapy and/or, ECT…)

Group Type: EXPERIMENTAL

Systematic maintenance rTMS

Intervention Type: DEVICE

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.

rTMS course in case of relapse (arm B)

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…)

Group Type: EXPERIMENTAL

rTMS course in case of relapse

Intervention Type: DEVICE

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.

Sham rTMS (arm C)

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…)

Group Type: SHAM_COMPARATOR

sham rTMS

Intervention Type: DEVICE

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.

Interventions

Systematic maintenance rTMS

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.

Intervention Type: DEVICE

rTMS course in case of relapse

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.

Intervention Type: DEVICE

sham rTMS

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.

Intervention Type: DEVICE

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)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Nantes University Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Samuel Bulteau, MD

Role: PRINCIPAL_INVESTIGATOR

Nantes University Hospital

Locations

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

Nantes University Hospital

Nantes, , France

EPS de Ville-Evrard

Neuilly-sur-Marne, , France

GH PItié Salpétrière

Paris, , France

GHU Psychiatrie Ste Anne

Paris, , France

CH Henri Laborit (Poitiers)

Poitiers, , France

Centre hospitalier Guillaume Regnier Rennes

Rennes, , France

CH du Rouvray - Rouen

Rouen, , France

CHU de Toulouse

Toulouse, , France

CHU de Tours / CHRU de Tours

Tours, , France

Countries

France

References

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.

Reference Type: DERIVED

PMID: 32248820 (View on PubMed)

Other Identifiers

RC17_0494

Identifier Type: -

Identifier Source: org_study_id