Elsevier

Clinical Neurophysiology

Volume 125, Issue 11, November 2014, Pages 2150-2206
Clinical Neurophysiology

Evidence-based guidelines on the therapeutic use of repetitive transcranial magnetic stimulation (rTMS)

https://doi.org/10.1016/j.clinph.2014.05.021Get rights and content

Highlights

  • Numerous studies have shown that repetitive transcranial magnetic stimulation (rTMS) produced significant clinical effects in patients with various neurological and psychiatric disorders.

  • This review presents guidelines on the therapeutic use of rTMS issued by a group of European experts.

  • Level A or B evidence supports an efficacy of rTMS protocols in depression, pain, motor stroke and schizophrenia.

Abstract

A group of European experts was commissioned to establish guidelines on the therapeutic use of repetitive transcranial magnetic stimulation (rTMS) from evidence published up until March 2014, regarding pain, movement disorders, stroke, amyotrophic lateral sclerosis, multiple sclerosis, epilepsy, consciousness disorders, tinnitus, depression, anxiety disorders, obsessive-compulsive disorder, schizophrenia, craving/addiction, and conversion. Despite unavoidable inhomogeneities, there is a sufficient body of evidence to accept with level A (definite efficacy) the analgesic effect of high-frequency (HF) rTMS of the primary motor cortex (M1) contralateral to the pain and the antidepressant effect of HF-rTMS of the left dorsolateral prefrontal cortex (DLPFC). A Level B recommendation (probable efficacy) is proposed for the antidepressant effect of low-frequency (LF) rTMS of the right DLPFC, HF-rTMS of the left DLPFC for the negative symptoms of schizophrenia, and LF-rTMS of contralesional M1 in chronic motor stroke. The effects of rTMS in a number of indications reach level C (possible efficacy), including LF-rTMS of the left temporoparietal cortex in tinnitus and auditory hallucinations. It remains to determine how to optimize rTMS protocols and techniques to give them relevance in routine clinical practice. In addition, professionals carrying out rTMS protocols should undergo rigorous training to ensure the quality of the technical realization, guarantee the proper care of patients, and maximize the chances of success. Under these conditions, the therapeutic use of rTMS should be able to develop in the coming years.

Section snippets

Principles

In 1831, Michael Faraday stated his law establishing that a time-varying current creates a magnetic field which, in turn, can induce an electric field and hence a secondary current within a nearby conducting medium. One hundred and fifty years later, Barker et al. (1985) proposed the first magnetic stimulator designed to stimulate the human brain transcranially, providing the prerequisite for subsequent clinical use of transcranial magnetic stimulation (TMS) (Barker, 1999). A number of TMS

Clinical applications of rTMS: methodology followed to derive the present guidelines

For each possible indication, bibliographic research was carried out independently by several experts, using 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, used in a previous French version of the guidelines (Lefaucheur et al., 2011a) and derived from those proposed by the European Federation of Neurological Societies (Brainin et al.,

Pain

The present literature review and recommendations exclusively concern ongoing chronic pain and therefore exclude publications on the use of rTMS to relieve provoked acute or experimental pain, which has been reviewed elsewhere (Mylius et al., 2012b). Chronic pain can be neuropathic (originating from a lesion or disease of somatosensory systems, either peripheral or central), non-neuropathic (due to an excess of nociception secondary to inflammation or tissue lesion, or psychogenic), or without

Movement disorders

The bibliography on the use of rTMS in movement disorders is particularly extensive, with more than one hundred references, mainly concerning PD (Edwards et al., 2008). A number of these studies have, however, been discarded for this review due to various methodological limitations. First, the potential application of rTMS has not been considered in this work unless it was supported by at least 2 studies published by 2 independent research groups. Thus, despite the amount of published work, the

Stroke

The use of rTMS for therapeutic purposes or as part of a neurorehabilitation strategy for stroke recovery is relatively recent and the first clinical trials were begun in 2001 (see historical background in Hummel et al., 2008). Application of cortical stimulation in stroke is aimed at either correcting maladaptive brain plasticity induced by the cerebrovascular accident or enhancing adaptive brain plasticity during rehabilitation. This goal may be achieved by locally modifying cortical

Amyotrophic lateral sclerosis

The rationale for using rTMS as a therapeutic tool in amyotrophic lateral sclerosis (ALS) is based on the hypothesis that these protocols are capable of reducing motor cortex excitability and, thus, it would be theoretically possible to antagonize excitoxicity of an enhanced glutamate transmission in the motor corticospinal system. Moreover, it has been demonstrated that rTMS may modulate plasma levels of brain-derived neurotrophic factor (BDNF), a potent survival factor for motor neurons, in

Multiple sclerosis

A PubMed search (keywords: rTMS/TBS AND multiple sclerosis) identified 15 papers, but only 3 papers addressed therapeutic issues. In these 3 studies, performed by the same group, the effects of a 2-week protocol of 5 Hz rTMS delivered over the motor cortex were found to be beneficial for: (i) hand dexterity in a series of 8 multiple sclerosis patients with cerebellar symptoms (Koch et al., 2008c); (ii) lower limb spasticity in a series of 19 patients with relapsing-remitting multiple sclerosis (

Epilepsy

About 20% of patients with primary generalized epilepsy and up to 60% of patients with focal epilepsy do not respond adequately to antiepileptic drugs and develop drug-resistant epilepsy (Pati and Alexopoulos, 2010). Some of these patients may benefit from surgical treatment based on the resection of the epileptogenic zone. For the rest of the patients, it is important to develop alternative treatments, including neurostimulation techniques. Since rTMS modulates cortical excitability, which

Disorders of consciousness

An emerging, clinical application of rTMS focuses on chronic disorders of consciousness, a term currently used in the literature to indicate either a vegetative state (VS) or a minimally conscious state. A PubMed search (keywords: rTMS/TBS AND vegetative state OR disorders of consciousness) identified 9 papers, but no sham-controlled studies were found. Two case reports suggested the possibility that HF rTMS might produce some arousal in permanent VS patients, associated with an improvement of

Alzheimer’s disease

A PubMed search (keywords: rTMS/TBS AND Alzheimer’s disease) identified 48 papers. While several rTMS studies addressed the question of cortical excitability changes in patients with Alzheimer’s disease, only few data are available on the possible clinical impact of rTMS protocols in these patients. First, the effect of HF rTMS delivered to the right or left DLPFC on language abilities, especially naming accuracy, and sentence comprehension has been assessed, showing positive results (Cotelli

Tinnitus

The use of rTMS in the treatment of tinnitus stems from the development of models of central generation and maintenance of disabling subjective tinnitus (Langguth et al., 2003, Plewnia et al., 2003). Tinnitus usually follows acute or chronic cochlear injury or disease (acoustic trauma, drug toxicity, presbyacusis) and its neural correlates reflect central changes induced by auditory deafferentation (neural plasticity with hypersynchrony or hyperactivity of cortical and subcortical auditory and

rTMS and psychiatry: general considerations

For 20 years, many studies have suggested that rTMS could be efficacious in the treatment of major depression and other psychiatric indications. This literature has gradually expanded and the methodological quality of work has improved along with the changes in stimulation protocols. Given its potential efficacy and its ease-of-use, the place of this technique in the therapeutic armamentarium at our disposal is an important issue, especially since several countries outside Europe (USA, Canada,

Depression

According to studies conducted in the general population, depression is a common mental condition with an annual prevalence ranging between 5% and 15%. Unfortunately, not all patients respond to the available pharmacological treatment algorithms (Fava, 2003, Nemeroff, 2007). The French Agency for Sanitary Safety of Health Products (AFSSAPS) indicated that about one-third of patients do not respond to an initial antidepressant treatment after 4–8 weeks of treatment (”On the good use of

Anxiety disorders

Anxiety disorders such as posttraumatic stress disorder (PTSD) and panic disorder (PaD) are currently treated by antidepressant drugs or psychotherapy, including cognitive behavioral therapies that have proven their efficacy. However, in some patients, these treatments are insufficient to control symptoms. Thus, rTMS could, on theoretical grounds, be a potential second-line technique to treat residual anxiety symptoms.

Obsessive compulsive disorder

Several therapeutic studies have been conducted in this indication. Published studies to date employed very heterogeneous methodologies, reflecting the various hypotheses on the underlying pathophysiological mechanisms. A PubMed search (keywords: rTMS/TBS AND obsessive-compulsive disorder) identified 48 papers, including 9 original placebo-controlled studies with at least 10 patients who received active rTMS of the DLPFC (Table 11). The analyzed results cover 215 patients.

The results of these

Auditory hallucinations

During auditory hallucinations, brain areas involved in the perception of speech (primary auditory cortex and associative areas of language in the left hemisphere) show pathological hyperactivity, as determined by neuroimaging studies (Silbersweig et al., 1995, Shergill et al., 2000). Decreasing the excitability of the TPC by LF rTMS became therefore an interesting line of research for the treatment of drug-resistant auditory hallucinations (Hoffman et al., 1999).

A PubMed search (keywords:

Substance abuse, addiction and craving

Abuse and addiction to substances, such as alcohol, nicotine, cocaine, or other drugs, are major health issues. These disorders are difficult to treat and the relapse rate is high, even following detoxification, pharmacological and psychological interventions (Fant et al., 2009, Heinz et al., 2009). The rationale to use rTMS 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, is

Conversion

Regarding functional neurological symptoms such as motor conversion disorder, a PubMed search (keywords: rTMS/TBS AND conversion) identified 23 papers, but no blinded or placebo-controlled study. There were mostly case reports following the pioneering work of Schönfeldt-Lecuona et al., 2003, Schönfeldt-Lecuona et al., 2006, and less than 10 studies have been published to date (reviewed in Pollak et al., 2014). Stimulation sites were essentially the motor cortex and the vertex, targeted using a

Summary of recommendations

This work presents for the first time an extensive evidence-based synthesis of established and potential therapeutic applications of rTMS in the neurological, ENT, and psychiatric domains. According to this synthesis, there is a sufficient level of evidence to recommend specific rTMS protocols in clinical practice for several indications, as summarized in Table 15.

It should be emphasized that a Level A recommendation has only been achieved so far for the beneficial effect of HF rTMS on

Acknowledgments

Massimo Cincotta and Simone Rossi have received grants from EBNeuro S.p.A, Florence, Italy. Hartwig Siebner and Simone Rossi have received travel support from MagVenture, Farum, Denmark and Magstim Co., Whitland, Carmarthenshire, UK, respectively. The other authors have no conflicting interests related to this article to declare.

Sasa Filipovic was supported by the Project Grant (OI 175012) from the Ministry for Education, Science, and Technological Development of the Republic of Serbia. Josep

References (761)

  • D.H. Avery et al.

    A controlled study of repetitive transcranial magnetic stimulation in medication-resistant major depression

    Biol Psychiatry

    (2006)
  • F. Awiszus

    TMS and threshold hunting

    Suppl Clin Neurophysiol

    (2003)
  • E.H. Bae et al.

    Safety and tolerability of repetitive transcranial magnetic stimulation in patients with epilepsy: a review of the literature

    Epilepsy Behav

    (2007)
  • E.H. Bae et al.

    An estimate of placebo effect of repetitive transcranial magnetic stimulation in epilepsy

    Epilepsy Behav

    (2011)
  • C. Baeken et al.

    Intensive HF-rTMS treatment in refractory medication-resistant unipolar depressed patients

    J Affect Disord

    (2013)
  • M. Bajbouj et al.

    Repetitive transcranial magnetic stimulation of the dorsolateral prefrontal cortex and cortical excitability in patients with major depressive disorder

    Exp Neurol

    (2005)
  • H. Barbas

    Connections underlying the synthesis of cognition, memory, and emotion in primate prefrontal cortices

    Brain Res Bull

    (2000)
  • M. Bares et al.

    Low frequency (1-Hz), right prefrontal repetitive transcranial magnetic stimulation (rTMS) compared with venlafaxine ER in the treatment of resistant depression: a double-blind, single-centre, randomized study

    J Affect Disord

    (2009)
  • A. Barker et al.

    Non invasive magnetic stimulation of the human motor cortex

    Lancet

    (1985)
  • M.S. Barr et al.

    A randomized controlled trial of sequentially bilateral prefrontal cortex repetitive transcranial magnetic stimulation in the treatment of negative symptoms in schizophrenia

    Brain Stimul

    (2012)
  • C.H. Barwood et al.

    Improved receptive and expressive language abilities in nonfluent aphasic stroke patients after application of rTMS: an open protocol case series

    Brain Stimul

    (2012)
  • S. Baudic et al.

    Unilateral repetitive transcranial magnetic stimulation of the motor cortex does not affect cognition in patients with fibromyalgia

    J Psychiatr Res

    (2013)
  • M.F. Bear et al.

    Neocortical long-term potentiation

    Curr Opin Neurobiol

    (1993)
  • F. Benedetti

    No prefrontal control, no placebo response

    Pain

    (2010)
  • D.H. Benninger

    Parkinson’s disease

    Handb Clin Neurol

    (2013)
  • D.H. Benninger et al.

    Safety study of 50 Hz repetitive transcranial magnetic stimulation in patients with Parkinson’s disease

    Clin Neurophysiol

    (2009)
  • M.T. Berlim et al.

    Repetitive transcranial magnetic stimulation (rTMS) for obsessive-compulsive disorder (OCD): an exploratory meta-analysis of randomized and sham-controlled trials

    J Psychiatr Res

    (2013)
  • R.M. Berman et al.

    A randomized clinical trial of repetitive transcranial magnetic stimulation in the treatment of major depression

    Biol Psychiatry

    (2000)
  • S. Bestmann et al.

    BOLD MRI responses to repetitive TMS over human dorsal premotor cortex

    Neuroimage

    (2005)
  • A. Beuter et al.

    Closed-loop cortical neuromodulation in Parkinson’s disease: An alternative to deep brain stimulation?

    Clin Neurophysiol

    (2014)
  • D.M. Blumberger et al.

    MRI-targeted repetitive transcranial magnetic stimulation of Heschl’s gyrus for refractory auditory hallucinations

    Brain Stimul

    (2012)
  • J.J. Borckardt et al.

    Significant analgesic effects of one session of postoperative left prefrontal cortex repetitive transcranial magnetic stimulation: a replication study

    Brain Stimul

    (2008)
  • M. Bortolomasi et al.

    Long-lasting effects of high frequency repetitive transcranial magnetic stimulation in major depressed patients

    Psychiatry Res

    (2007)
  • D. Bouhassira et al.

    Prevalence of chronic pain with neuropathic characteristics in the general population

    Pain

    (2008)
  • N.N. Boutros et al.

    Lack of a therapeutic effect of a 2-week sub-threshold transcranial magnetic stimulation course for treatment-resistant depression

    Psychiatry Res

    (2002)
  • L.S. Boylan et al.

    Repetitive transcranial magnetic stimulation to SMA worsens complex movements in Parkinson’s disease

    Clin Neurophysiol

    (2001)
  • F. Brighina et al.

    1 Hz repetitive transcranial magnetic stimulation of the unaffected hemisphere ameliorates contralesional visuospatial neglect in humans

    Neurosci Lett

    (2003)
  • F. Brighina et al.

    rTMS of the prefrontal cortex in the treatment of chronic migraine: a pilot study

    J Neurol Sci

    (2004)
  • F. Brighina et al.

    Hemispheric cerebellar rTMS to treat drug-resistant epilepsy: case reports

    Neurosci Lett

    (2006)
  • M. Abo et al.

    Effectiveness of low-frequency rTMS and intensive speech therapy in poststroke patients with aphasia: a pilot study based on evaluation by fMRI in relation to type of aphasia

    Eur Neurol

    (2012)
  • S.J. Ackerley et al.

    Combining theta burst stimulation with training after subcortical stroke

    Stroke

    (2010)
  • B.O. Adeyemo et al.

    Systematic review of parameters of stimulation, clinical trial design characteristics, and motor outcomes in non-invasive brain stimulation in stroke

    Front Psychiatry

    (2012)
  • R. Ahdab et al.

    Reappraisal of the anatomical landmarks of motor and premotor cortical regions for image-guided brain navigation in TMS practice

    Hum Brain Mapp

    (2014)
  • M.A. Ahmed et al.

    Long-term antalgic effects of repetitive transcranial magnetic stimulation of motor cortex and serum beta-endorphin in patients with phantom pain

    Neurol Res

    (2011)
  • M.A. Ahmed et al.

    Effects of low versus high frequencies of repetitive transcranial magnetic stimulation on cognitive function and cortical excitability in Alzheimer’s dementia

    J Neurol

    (2012)
  • A. Aleman et al.

    Efficacy of slow repetitive transcranial magnetic stimulation in the treatment of resistant auditory hallucinations in schizophrenia: a meta-analysis

    J Clin Psychiatry

    (2007)
  • N. Allam et al.

    Relief of primary cervical dystonia symptoms by low frequency transcranial magnetic stimulation of the premotor cortex: case report

    Arq Neuropsiquiatr

    (2007)
  • P. Alonso et al.

    Right prefrontal repetitive transcranial magnetic stimulation in obsessive-compulsive disorder: a double-blind, placebo-controlled study

    Am J Psychiatry

    (2001)
  • M. Ameli et al.

    Differential effects of high-frequency repetitive transcranial magnetic stimulation over ipsilesional primary motor cortex in cortical and subcortical middle cerebral artery stroke

    Ann Neurol

    (2009)
  • R. Amiaz et al.

    Repeated high-frequency transcranial magnetic stimulation over the dorsolateral prefrontal cortex reduces cigarette craving and consumption

    Addiction

    (2009)
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