Evidence-based guidelines on the therapeutic use of transcranial direct current stimulation (tDCS)

https://doi.org/10.1016/j.clinph.2016.10.087Get rights and content

Highlights

  • A group of European experts reviewed current evidence for therapeutic efficacy of tDCS.

  • Level B evidence (probable efficacy) was found for fibromyalgia, depression and craving.

  • The therapeutic relevance of tDCS needs to be further explored in these and other indications.

Abstract

A group of European experts was commissioned by the European Chapter of the International Federation of Clinical Neurophysiology to gather knowledge about the state of the art of the therapeutic use of transcranial direct current stimulation (tDCS) from studies published up until September 2016, regarding pain, Parkinson’s disease, other movement disorders, motor stroke, poststroke aphasia, multiple sclerosis, epilepsy, consciousness disorders, Alzheimer’s disease, tinnitus, depression, schizophrenia, and craving/addiction. The evidence-based analysis included only studies based on repeated tDCS sessions with sham tDCS control procedure; 25 patients or more having received active treatment was required for Class I, while a lower number of 10–24 patients was accepted for Class II studies. Current evidence does not allow making any recommendation of Level A (definite efficacy) for any indication. Level B recommendation (probable efficacy) is proposed for: (i) anodal tDCS of the left primary motor cortex (M1) (with right orbitofrontal cathode) in fibromyalgia; (ii) anodal tDCS of the left dorsolateral prefrontal cortex (DLPFC) (with right orbitofrontal cathode) in major depressive episode without drug resistance; (iii) anodal tDCS of the right DLPFC (with left DLPFC cathode) in addiction/craving. Level C recommendation (possible efficacy) is proposed for anodal tDCS of the left M1 (or contralateral to pain side, with right orbitofrontal cathode) in chronic lower limb neuropathic pain secondary to spinal cord lesion. Conversely, Level B recommendation (probable inefficacy) is conferred on the absence of clinical effects of: (i) anodal tDCS of the left temporal cortex (with right orbitofrontal cathode) in tinnitus; (ii) anodal tDCS of the left DLPFC (with right orbitofrontal cathode) in drug-resistant major depressive episode. It remains to be clarified whether the probable or possible therapeutic effects of tDCS are clinically meaningful and how to optimally perform tDCS in a therapeutic setting. In addition, the easy management and low cost of tDCS devices allow at home use by the patient, but this might raise ethical and legal concerns with regard to potential misuse or overuse. We must be careful to avoid inappropriate applications of this technique by ensuring rigorous training of the professionals and education of the patients.

Section snippets

Principles and mechanisms of action of transcranial direct current stimulation

Alterations of neuroplasticity and cortical excitability are important pathophysiological factors in many neuropsychiatric diseases. Thus, to modify cortical activities by using non-invasive brain stimulation (NIBS) might be a valuable therapeutic approach. One of these NIBS approaches is transcranial direct current stimulation (tDCS). Fifty years ago, it has been demonstrated in anesthetized rats that neural activity and cortical excitability could be modified by the application of direct

Clinical applications of tDCS: literature data analysis

For each potential clinical indication of tDCS, a bibliographic search was carried out by several experts independently, using specific keywords that will be specified at the beginning of each section. Each expert then proceeded to a critical reading of all selected publications in order to classify them according to the following criteria, derived from those proposed by the European Federation of Neurological Societies (Brainin et al., 2004). First, the studies were classified (I–IV) according

Pain

The literature review included studies related to ongoing chronic pain, or acute postoperative pain, and therefore excludes publications on the use of tDCS to relieve pain experimentally induced in healthy subjects, reviewed elsewhere (Mylius et al., 2012). A PubMed search [keywords: tDCS AND (pain OR migraine)] identified 269 papers, including 62 original clinical studies covering 1426 patients. In all indications, we first screened literature data for original clinical trials, excluding any

Parkinson’s disease

In advanced Parkinson’s disease (PD), the emergence of fluctuations, dyskinesias, difficulties with gait and postural control, cognitive impairment and non-motor symptoms refractory to conventional therapy poses therapeutic challenges. The success of deep brain stimulation (DBS) and advances in the understanding of the pathophysiology of PD have raised interest in NIBS techniques as alternative therapeutic tool. The rationale for the use of NIBS draws from the concept that reversing

Other movement disorders

Actually, published tDCS studies on movement disorders other than PD are rare and have been recently reviewed (Ferrucci et al., 2016). There are only two sham-controlled crossover studies using repeated tDCS sessions. The first study concerned 8 patients with essential tremor who completed a tDCS protocol for 10 days with two cathodes placed over both cerebellar hemispheres and two anodes positioned over both prefrontal areas (Gironell et al., 2014). In this study, any short- or long-lasting

Motor stroke

The recovery of motor function after stroke is one of the most important issues addressed in neurorehabilitation medicine. The rationale of cortical stimulation following stroke is to promote adaptive neuroplasticity, taking place in the perilesional region as well as in the homologous area of the contralesional hemisphere. Functional magnetic resonance imaging (fMRI) studies have revealed an initial decrease in ipsilesional activity in the first 3 days after stroke followed by an increase in

Aphasia

Aphasia is a highly disabling language disorder frequently caused by a left-lateralized hemispheric stroke (Laska et al., 2001). Even if traditional linguistic-based therapies have been proved to induce an adequate clinical improvement (Basso et al., 2011, Code and Petheram, 2011, Brady et al., 2012), a large percentage of patients are left with some degree of language impairment (Lazar et al., 2010). It has been suggested that one of the key predictors for positive language outcomes is

Multiple sclerosis

Multiple sclerosis (MS) is one of the most common neurological diseases and a serious cause of disability in young adults. Its natural course is characterized by recurrent relapses or progressive functional decline. With disease evolution, patients could accumulate several neurological dysfunctions or disease-related complications including motor deficit, fatigue, tremor, spasticity, sensory disturbances, pain, genital or urinary symptoms, and psychiatric or cognitive disorders. Many of these

Epilepsy

Although NIBS techniques aimed at modifying cortical excitability, the study of their therapeutic potential in epilepsy remains underdeveloped. This is the case for rTMS (Lefaucheur et al., 2014) and even more for tDCS. Actually, a PubMed search (keywords: tDCS AND Epilepsy) identified 65 papers, including only 10 original clinical studies and 147 patients. Moreover, 5 of these studies were case reports of 1–5 patients, while 5 sham-controlled studies with crossover or parallel-arm design

Disorders of consciousness

Disorders of consciousness, such as minimally conscious state (MCS) and vegetative state (VS), are highly challenging clinical conditions for treatment. A PubMed search (keywords: tDCS AND vegetative state OR disorders of consciousness) identified 23 papers, including 4 original clinical studies and 79 patients. These four studies included 10, 30, 25, and 14 patients, respectively (Angelakis et al., 2014, Thibaut et al., 2014, Naro et al., 2015, Naro et al., 2016). The left DLPFC was targeted

Alzheimer’s disease

Since its updating in the early 2000s, tDCS has been widely used in neuropsychological studies to act on cognitive and behavioural features, e.g., attention, memory and working memory, computation, decision-making, and so on, in either healthy humans or patients with various neuropsychiatric diseases (Shin et al., 2015, Hill et al., 2016). Therefore, there are a lot of expectations regarding the therapeutic potential of tDCS to modulate psychological processes in cognitive disorders, such as

Tinnitus

Tinnitus is a phantom perception of a sound in the absence of a corresponding external sound source and occurs in 5–15% of the population (Axelsson and Ringdahl, 1989, Heller, 2003, Gallus et al., 2015). Whereas many patients can habituate to this sound, quality of life is severely disrupted in about 25% of the patients who cannot cope with the tinnitus (Axelsson and Ringdahl, 1989). In these patients, tinnitus is frequently associated with anxiety, depression, cognitive impairment, and sleep

Depression

The rationale for the use of tDCS in the treatment of depressive disorders is based on the knowledge of functional and structural abnormalities in the left and right dorsolateral and ventromedial prefrontal cortex, amygdala and hippocampus in depressed patients (Campbell et al., 2004, Hamilton et al., 2008, Koenigs and Grafman, 2009). The aim of the NIBS techniques is to normalize the interhemispheric imbalance of neuronal activity between the both DLPFC areas, which was highlighted in this

Schizophrenia

Despite advances in psychopharmacology, the majority of treated patients with schizophrenia retain disabling symptoms. The most frequent drug-resistant symptoms are auditory verbal hallucinations (AVH) and various negative symptoms (e.g., avolition, alogia, or emotional withdrawal). Neuroimaging and neurophysiological studies have highlighted that these refractory symptoms may be linked to a fronto-temporal dysconnectivity. Negative symptoms and AVH have been related to a reduced brain activity

Substance abuse, addiction and craving

Addiction to substances such as alcohol, drugs, nicotine, or food, is a major health issue, because of the difficulty to achieve a permanent cure with a high rate of relapses, despite detoxification and pharmacological or psychological interventions (Fant et al., 2009, Heinz et al., 2009). The rationale of using tDCS as a treatment for substance addiction and craving is that the DLPFC, which plays a major role in top-down inhibitory control mechanisms and reward mechanisms, was claimed to be

Other psychiatric disorders

Regarding clinical applications of tDCS in psychiatric disorders other than depression, schizophrenia and addiction, there are only very limited data available in the literature. A PubMed search (keywords: tDCS AND obsessive compulsive disorder) identified 17 papers, including 5 original clinical studies and 12 patients. There were 4 single case reports and only one open-label study performed on 8 patients with the cathode placed over the left orbitofrontal cortex and the anode placed over the

At-home do-it-yourself DCS and neural enhancement

One of the main advantages of tDCS as a therapeutic device is to be a low-cost, small-size, and patient-wearable equipment. Also, it allows distribution of machines for home use, which is not the case for rTMS. Although therapeutic effects may last beyond the time of stimulation when using NIBS techniques because of neural plasticity processes, the treatment of a chronic disease always requires repeated sessions in a maintenance protocol. Considering rTMS, this is resulting in multiple trips

Perspectives of targets other than cortical (cerebellum and spinal cord)

Although this work is intended to be a guideline on the indications of tDCS applied to the cerebral cortex, readers should be informed that research currently develops to explore the possibility of using transcutaneous DC stimulation on other neural targets, such as cerebellum and spinal cord, in order to promote functional neural changes (Priori et al., 2014). This issue will be briefly addressed.

Perspectives of treatment by transcranial electrical stimulation methods other than tDCS (tACS, tRNS)

Although the present work addresses tDCS results, we should also mention that future developments with potential therapeutic application might regard other non-invasive neuromodulation techniques using low-intensity transcranial electrical stimulation. We briefly present these other techniques, namely tACS and tRNS, which are for now the subject of relatively few clinical studies. Taking into account all physical possibilities, an indefinite number of transcranial electrical stimulation

Summary of recommendations

This work presents for the first time a comprehensive evidence-based analysis of the reported clinical efficacy of various tDCS montages that could lead to therapeutic applications in the neurological, otorhinolaryngological, and psychiatric domains. According to this synthesis, there is a sufficient level of evidence to make recommendations for the efficacy of specific tDCS montages in several clinical indications, as summarized in Table 11.

To date, a Level A recommendation has not been

Conflict of interest

Michael A. Nitsche is member of the advisory board of Neuroelectrics, Barcelona, Spain. Simone Rossi have received grants from EBNeuro S.p.A, Florence, Italy and travel support from MagVenture, Farum, Denmark and Magstim Co., Whitland, Carmarthenshire, UK, respectively. Walter Paulus is on the scientific advisory board of EBS technologies, Berlin, Germany. Frank Padberg has received speaker honorarium from Mag&More GmbH, Munich, Germany and equipment support from neuroConn GmbH, Ilmenau,

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