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.

Hospital production cost of transcranial direct current stimulation (tDCS) in the treatment of depression.

OBJECTIVES: Due to its ease of use, tolerance, and cost of acquisition, transcranial direct current stimulation (tDCS) could constitute a credible therapeutic option for non-resistant depression in primary care, when combined with drug management. This indication has yet to receive official recognition in France. The objective of this study is to evaluate the production cost of tDCS for the treatment of depression in hospitals, under realistic conditions. METHODS: The methodology adopted is based on cost accounting and was validated by a multidisciplinary working group. It includes equipment, staff, and structural costs to obtain the most realistic estimate possible. We first estimated the cost of producing a tDCS session, based on our annual activity objective, and then estimated the cost of a 15-session treatment program. This was followed up with a sensitivity analysis applying appropriate parameters. RESULTS: The hospital production cost of a tDCS depression treatment program for a single patient was estimated at €1555.60 euros: €99 in equipment costs, €1076.95 in staff costs, and €379.65 in structural costs. CONCLUSION: This cost analysis should make it possible to draw up pricing proposals in compliance with regulations and health policy choices and to develop health-economic studies. This would ultimately lead to official recognition of tDCS treatment for depression in France and pave the way for studying various scenarios of coverage by the French national health insurance system.

Brain and spinal stimulation therapies for phantom limb pain: a systematic review.

BACKGROUND: Although many treatments exist for phantom limb pain (PLP), the evidence supporting them is limited and there are no guidelines for PLP management. Brain and spinal cord neurostimulation therapies are targeted at patients with chronic PLP but have yet to be systematically reviewed. OBJECTIVE: To determine which types of brain and spinal stimulation therapy appear to be the best for treating chronic PLP. DESIGN: Systematic reviews of effectiveness and epidemiology studies, and a survey of NHS practice. POPULATION: All patients with PLP. INTERVENTIONS: Invasive interventions - deep brain stimulation (DBS), motor cortex stimulation (MCS), spinal cord stimulation (SCS) and dorsal root ganglion (DRG) stimulation. Non-invasive interventions - repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS). MAIN OUTCOME MEASURES: Phantom limb pain and quality of life. DATA SOURCES: Twelve databases (including MEDLINE and EMBASE) and clinical trial registries were searched in May 2017, with no date limits applied. REVIEW METHODS: Two reviewers screened titles and abstracts and full texts. Data extraction and quality assessments were undertaken by one reviewer and checked by another. A questionnaire was distributed to clinicians via established e-mail lists of two relevant clinical societies. All results were presented narratively with accompanying tables. RESULTS: Seven randomised controlled trials (RCTs), 30 non-comparative group studies, 18 case reports and 21 epidemiology studies were included. Results from a good-quality RCT suggested short-term benefits of rTMS in reducing PLP, but not in reducing anxiety or depression. Small randomised trials of tDCS suggested the possibility of modest, short-term reductions in PLP. No RCTs of invasive therapies were identified. Results from small, non-comparative group studies suggested that, although many patients benefited from short-term pain reduction, far fewer maintained their benefits. Most studies had important methodological or reporting limitations and few studies reported quality-of-life data. The evidence on prognostic factors for the development of chronic PLP from the longitudinal studies also had important limitations. The results from these studies suggested that pre-amputation pain and early PLP intensity are good predictors of chronic PLP. Results from the cross-sectional studies suggested that the proportion of patients with severe chronic PLP is between around 30% and 40% of the chronic PLP population, and that around one-quarter of chronic PLP patients find their PLP to be either moderately or severely limiting or bothersome. There were 37 responses to the questionnaire distributed to clinicians. SCS and DRG stimulation are frequently used in the NHS but the prevalence of use of DBS and MCS was low. Most responders considered SCS and DRG stimulation to be at least sometimes effective. Neurosurgeons had mixed views on DBS, but most considered MCS to rarely be effective. Most clinicians thought that a randomised trial design could be successfully used to study neurostimulation therapies. LIMITATION: There was a lack of robust research studies. CONCLUSIONS: Currently available studies of the efficacy, effectiveness and safety of neurostimulation treatments do not provide robust, reliable results. Therefore, it is uncertain which treatments are best for chronic PLP. FUTURE WORK: Randomised crossover trials, randomised N-of-1 trials and prospective registry trials are viable study designs for future research. STUDY REGISTRATION: The study is registered as PROSPERO CRD42017065387. FUNDING: The National Institute for Health Research Health Technology Assessment programme.

Noninvasive Brain Stimulation: Challenges and Opportunities for a New Clinical Specialty.

Noninvasive brain stimulation refers to a set of technologies and techniques with which to modulate the excitability of the brain via transcranial stimulation. Two major modalities of noninvasive brain stimulation are transcranial magnetic stimulation (TMS) and transcranial current stimulation. Six TMS devices now have approved uses by the U.S. Food and Drug Administration and are used in clinical practice: five for treating medication refractory depression and the sixth for presurgical mapping of motor and speech areas. Several large, multisite clinical trials are currently underway that aim to expand the number of clinical applications of noninvasive brain stimulation in a way that could affect multiple clinical specialties in the coming years, including psychiatry, neurology, pediatrics, neurosurgery, physical therapy, and physical medicine and rehabilitation. In this article, the authors review some of the anticipated challenges facing the incorporation of noninvasive brain stimulation into clinical practice. Specific topics include establishing efficacy, safety, economics, and education. In discussing these topics, the authors focus on the use of TMS in the treatment of medication refractory depression when possible, because this is the most widely accepted clinical indication for TMS to date. These challenges must be thoughtfully considered to realize the potential of noninvasive brain stimulation as an emerging specialty that aims to enhance the current ability to diagnose and treat disorders of the brain.

Transcranial direct current stimulation in post-stroke sub-acute aphasia: study protocol for a randomized controlled trial.

BACKGROUND: Transcranial direct current stimulation (tDCS) is a promising new technique to optimize the effect of regular Speech and Language Therapy (SLT) in the context of aphasia rehabilitation. The present study focuses on the effect of tDCS provided during SLT in the sub-acute stage after stroke. The primary aim is to evaluate the potential effect of tDCS on language functioning, specifically on word-finding, as well as generalization effects to verbal communication. The secondary aim is to evaluate its effect on social participation and quality of life, and its cost-effectiveness. METHODS: We strive to include 58 stroke patients with aphasia, enrolled in an inpatient or outpatient stroke rehabilitation program, in a multicenter, double-blind, randomized controlled trial with two parallel groups and 6 months' follow-up. Patients will participate in two separate intervention weeks, with a pause of 2 weeks in between, in the context of their regular aphasia rehabilitation program. The two intervention weeks comprise daily 45-minute sessions of word-finding therapy, combined with either anodal tDCS over the left inferior frontal gyrus (1 mA, 20 minutes; experimental condition) or sham-tDCS over the same region (control condition). The primary outcome measure is word-finding. Secondary outcome measures are verbal communication, social participation, quality of life, and cost-effectiveness of the intervention. DISCUSSION: Our results will contribute to the discussion on whether tDCS should be implemented in regular aphasia rehabilitation programs for the sub-acute post-stroke population in terms of (cost-)effectiveness. TRIAL REGISTRATION: Nederlands Trail Register: NTR4364 . Registered on 21 February 2014.