Cost-utility analysis of transcranial direct current stimulation (tDCS) in non-treatment-resistant depression: the DISCO randomised controlled study protocol.

INTRODUCTION: Depression is among the most widespread psychiatric disorders in France. Psychiatric disorders are associated with considerable social costs, amounting to €22.6 billion for treatment and psychotropic medication in 2011. Treatment as usual (TAU), mainly consisting of pharmacotherapy and psychotherapy, is effective for only a third of patients and in most cases fails to prevent treatment resistance and chronicity. Transcranial direct current stimulation (tDCS) consists in a non-invasive and painless application of low-intensity electric current to the cerebral cortex through the scalp. Having proved effective in depressed patients, it could be used in combination with TAU to great advantage. The objective is to compare, for the first time ever, the cost-utility of tDCS-TAU and of TAU alone for the treatment of a depressive episode that has been refractory to one or two drug treatments. METHODS AND ANALYSIS: This paper, based on the DISCO study protocol, focuses on the design of a prospective, randomised, controlled, open-label multicentre economic study to be conducted in France. It will include 214 patients with unipolar or bipolar depression, assigning them to two parallel arms: group A (tDCS-TAU) and group B (TAU alone). The primary outcome is the incremental cost-effectiveness ratio, that is, the ratio of the difference in cost between each strategy to the difference in their effects. Their effects will be expressed as numbers of quality-adjusted life-years, determined through administration of the EuroQol Five-Dimension questionnaire over a 12-month period to patients (EQ-5D-5L). Expected benefits are the reduction of treatment resistance and suicidal ideation as well as social and professional costs of depression. Should depression-related costs fall significantly, tDCS might be considered an efficient treatment for depression. ETHICS AND DISSEMINATION: This protocol has been approved by a French ethics committee, the CPP--Est IV (Comité de Protection des Personnes-Strasbourg). Data are to be published in peer-reviewed medical journals. TRIAL REGISTRATION NUMBER: RCB 2018-A00474-51; NCT03758105.

Efficacy of intermittent Theta Burst Stimulation (iTBS) and 10-Hz high-frequency repetitive transcranial magnetic stimulation (rTMS) in treatment-resistant unipolar depression: study protocol for a randomised controlled trial.

BACKGROUND: The treatment of depression remains a challenge since at least 40% of patients do not respond to initial antidepressant therapy and 20% present chronic symptoms (more than 2 years despite standard treatment administered correctly). Repetitive transcranial magnetic stimulation (rTMS) is an effective adjuvant therapy but still not ideal. Intermittent Theta Burst Stimulation (iTBS), which has only been used recently in clinical practice, could have a faster and more intense effect compared to conventional protocols, including 10-Hz high-frequency rTMS (HF-rTMS). However, no controlled study has so far highlighted the superiority of iTBS in resistant unipolar depression. METHODS/DESIGN: This paper focuses on the design of a randomised, controlled, double-blind, single-centre study with two parallel arms, carried out in France, in an attempt to assess the efficacy of an iTBS protocol versus a standard HF- rTMS protocol. Sixty patients aged between 18 and 75 years of age will be enrolled. They must be diagnosed with major depressive disorder persisting despite treatment with two antidepressants at an effective dose over a period of 6 weeks during the current episode. The study will consist of two phases: a treatment phase comprising 20 sessions of rTMS to the left dorsolateral prefrontal cortex, localised via a neuronavigation system and a 6-month longitudinal follow-up. The primary endpoint will be the number of responders per group, defined by a decrease of at least 50% in the initial score on the Montgomery and Asberg Rating Scale (MADRS) at the end of rTMS sessions. The secondary endpoints will be: response rate 1 month after rTMS sessions; number of remissions defined by a MADRS score of <8 at the endpoint and 1 month after; the number of responses and remissions maintained over the next 6 months; quality of life; and the presence of predictive markers of the therapeutic response: clinical (dimensional scales), neuropsychological (evaluation of cognitive functions), motor (objective motor testing) and neurophysiological (cortical excitability measurements). DISCUSSION: The purpose of our study is to check the assumption of iTBS superiority in the management of unipolar depression and we will discuss its effect over time. In case of a significant increase in the number of therapeutic responses with a prolonged effect, the iTBS protocol could be considered a first-line protocol in resistant unipolar depression. TRIAL REGISTRATION: ClinicalTrials.gov, Identifier NCT02376491 . Registered on 17 February 2015 at http://clinicaltrials.gov .