Transcranial magnetic stimulation as a therapeutic tool in psychiatry.

Transcranial magnetic stimulation (TMS) is a patient-friendly stimulation technique of the brain with interesting perspectives. In clinical psychiatry, limited data are available on activity in psychosis and anxiety, but much research has been done in depression. Major concerns on published papers are the inconsistency of used parameter settings, the restraint numbers of patients in randomised trials, the lack of real sham controlled studies and the quasi inexistent reproducibility of results. The most stringent meta-analysis of TMS in affective disorders found a modest, statistically significant antidepressant effect after 2 weeks of daily treatment of high frequency repetitive left dorsolateral prefrontal cortex stimulation. Although most results are rather weak and not convincing enough to promote TMS as evidence-based antidepressive therapy, they show a measurable action that should not be ignored. Preclinical and clinical effects were observed analysing heterogeneous data, and results comparing TMS to electroconvulsive therapy (ECT) in affective disorders are encouraging. Efforts should continue with emphasis on increasing homogeneity and reproducibility in data. Further refinement of stimulation parameters should be established, so that new and large double-blind, long-term, sham-controlled trials can bring us to better understanding and standardising TMS procedure, finally leading to definitive conclusions about its efficacy in psychiatry.

Transcranial magnetic stimulation in neurorehabilitation.

In neurorehabilitation, transcranial magnetic stimulation (TMS) offers information regarding prognosis and pathophysiology and could also be useful for therapeutic purposes. Numerous studies have indicated that, after stroke, the absence of motor evoked potentials is associated with a poor motor recovery. In contrast, MEPs obtained in the paretic muscle with low stimulus intensities suggest a good restitution of motor function. TMS studies have shown that the location of a brain lesion determines motor cortex excitability changes: Patients with central somatosensory lesions show a disinhibition in the ipsilesional motor cortex. Lesions in the territory of the superior cerebellar artery are associated with a loss of motor cortex excitability. Stroke patients participating in a Constraint-induced movement therapy show an enlargement of the motor output area in the affected hemisphere after therapy. This enhancement of motor excitability is associated with an improvement of motor function. Some evidence is emerging that the application of low frequency repetitive TMS over the non-lesioned hemisphere improves neglect phenomena by down-regulation of the excitability of the non-lesioned hemisphere.

Antiepileptic effects of repetitive transcranial magnetic stimulation in patients with cortical malformations: an EEG and clinical study.

OBJECTIVE: To study the effects of repetitive transcranial magnetic stimulation (rTMS) on epileptic EEG discharges in patients with refractory epilepsy and malformations of cortical development (MCDs). METHODS: Eight patients with MCD and refractory epilepsy underwent 1 session of low-frequency rTMS (0.5 Hz, 600 pulses) focally targeting the MCD. The number of epileptiform discharges (EDs) in the EEG and seizures were measured before (baseline), immediately after as well as 15 and 30 days after rTMS treatment. RESULTS: Stimulation significantly decreased the number of EDs 15 and 30 days after rTMS treatment (mean reduction of 46.4%, 95% CI 12.7-80.2%, and mean reduction of 42.1%, 95% CI 8.2-75.7%, respectively). This was associated with a significant reduction in the number of seizures reported as compared with the 4-week period preceding rTMS (mean reduction of 57.3%, 95% CI 33.1-80.3%, and mean reduction of 51.2%, 95% CI 27.9-74.9%, respectively). CONCLUSION: This open study shows a significant antiepileptic effect of rTMS based on clinical and electrophysiological criteria and supports the therapeutic utility of rTMS for patients with well-localized epileptogenic cortical malformations.

Transcranial magnetic stimulation for patients with depression.

Transcranial magnetic stimulation (TMS) is a relatively new technique which has been used to treat depression. It delivers magnetic radiation to the head using a hand-held coil. Some studies have indicated clinical remission of depressive symptomatology with use of TMS. Methodological limitations remain, however, and more studies are recommended to determine its efficacy.

Temporoparietal transcranial magnetic stimulation for auditory hallucinations: safety, efficacy and moderators in a fifty patient sample.

BACKGROUND: Auditory hallucinations are often resistant to treatment and can produce significant distress and behavioral difficulties. A preliminary report based on 24 patients with schizophrenia or schizoaffective disorder indicated greater improvement in auditory hallucinations following 1-hertz left temporoparietal repetitive transcranial magnetic stimulation (rTMS) compared to sham stimulation. Data from the full 50-subject sample incorporating 26 new patients are now presented to more comprehensively assess safety/tolerability, efficacy and moderators of this intervention. METHODS: Right-handed patients experiencing auditory hallucinations at least 5 times per day were randomly allocated to receive either rTMS or sham stimulation. A total of 132 minutes of rTMS was administered over 9 days at 90% motor threshold using a double-masked, sham-controlled, parallel design. RESULTS: Hallucination Change Score was more improved for rTMS relative to sham stimulation (p = .008) as was the Clinical Global Impressions Scale (p = .0004). Hallucination frequency was significantly decreased during rTMS relative to sham stimulation (p = .0014) and was a moderator of rTMS effects (p = .008). There was no evidence of neurocognitive impairment associated with rTMS. CONCLUSIONS: Left temporoparietal 1-hertz rTMS warrants further study as an intervention for auditory hallucinations. Data suggest that this intervention selectively alters neurobiological factors determining frequency of these hallucinations.

Effect of transcranial magnetic stimulation on voluntary activation in patients with quadriceps weakness.

Joint disease causes weakness and wasting of adjacent muscles, in part because of inability to fully activate these muscles voluntarily. Previous findings suggest that transcranial magnetic stimulation (TMS) paired with muscle contractions enhances maximal voluntary contraction force (MVC) in healthy subjects by improving voluntary activation (VA). The aim of the present study was to evaluate whether such an effect is also present in subjects suffering from diminished muscle force due to decreased VA. Three single TMS over resting motor threshold were applied in 10 patients with a mean age of 62 years after total-knee arthroplasty either during MVC or during muscle relaxation (control experiment) in a blinded randomized crossover study. MVC and VA were determined using a twitch-interpolation technique at 1, 15, 30, and 60 min after stimulation. There was a significant effect of TMS on MVC if applied in synchrony with muscle contraction, and this persisted for at least 60 min beyond stimulation. In patients suffering from joint disease, TMS might make physiotherapy more effective.

Repetitive transcranial magnetic stimulation for treating medication-resistant depression in Taiwan: a preliminary study.

BACKGROUND: We conducted an open trial to evaluate the efficacy of repetitive transcranial magnetic stimulation (rTMS) in medication-resistant depression. This is the first study in Taiwan of rTMS for the treatment of depression. METHODS: A 2-week regimen of rTMS (100% of motor threshold, 5 Hz, 8 sec, 40 trains/20 min/day, 10 weekdays) applied to the left dorsolateral prefrontal cortex was administered to 11 patients with medication-resistant depression. RESULTS: Ten subjects completed 2 weeks' treatment with rTMS. Scores on the 21-item Hamilton Depression Rating Scale (HAM-D21) and Beck Depression Inventory decreased by 48% and 28%, respectively. Five patients were clinical responders (> or = 50% reduction in HAM-D21 score): 2 of these were in complete remission (HAM-D21 score < or = 7). Five patients were less responsive: 2 of these were partial responders (20-49% reduction in HAM-D21 score), whereas 3 did not improve. Younger versus older age was identified as a potential predictor of response to rTMS used as add-on therapy. CONCLUSION: Our preliminary results indicate that rTMS can improve mood in patients with medication-resistant depression, and can also potentially replace electroconvulsive therapy for certain types of medication-resistant depression. Future double-blind, placebo-controlled trials of rTMS are warranted.

[A new method for the treatment of depression: repetitive transcranial magnetic stimulation]. / Ein neues Behandlungsverfahren der Depression: Die repetitive transkranielle Magnetstimulation (rTMS).

Recent data suggest that repetitive transcranial magnetic stimulation (rTMS) is effective in treating depressive symptoms to a lesser extent compared with classical electroconvulsive therapy. However, rTMS represents an economical and well tolerable procedure in relation to the expenditure of electroconvulsive therapy with anaesthesia. Usually, rTMS is applicated as an add-on-therapy accompanying psychopharmacological treatment. So far, it has predominantly been used for patients with long-standing and so called treatment-refractory symptoms. However, even in the early phase of a depressive episode rTMS would be possibly more effective. In many cases, the standard procedure-application of up to 10 rTMS-sessions will not be enough to produce therapeutic benefit. Therefore rTMS series including up to 20 sessions are recommended. Long-term studies are needed to clarify the role of rTMS for relapse prevention and to determine the optimal frequency and duration of rTMS in such an indication. Although numerous results of newer studies suggest a moderate antidepressive effect of rTMS, its application in daily clinical routine practice cannot be recommended yet. Larger, accurate designed and controlled studies, especially involving patients of old age, are needed to evaluate the true tolerability and effectiveness of rTMS as a new treatment option for depressive symptoms.

Long-term effects of repetitive transcranial magnetic stimulation (rTMS) in patients with chronic tinnitus.

OBJECTIVES: The pathophysiologic mechanisms of idiopathic tinnitus remain unclear. Recent studies demonstrated focal brain activation in the auditory cortex of patients with chronic tinnitus. Low-frequency repetitive transcranial magnetic stimulation (rTMS) is able to reduce cortical hyperexcitability. STUDY DESIGN: Fusing of the individual PET-scan with the structural MRI-scan (T1, MPRAGE) allowed us to identify exactly the area of increased metabolic activity in the auditory cortex of patients with chronic tinnitus. With the use of a neuronavigational system, this target area was exactly stimulated by the figure 8-shaped magnetic coil. In a prospective study, rTMS (110% motor threshold; 1 Hz; 2000 stimuli/day over 5 days) was performed using a placebo controlled cross-over design. Patients were blinded regarding the stimulus condition. For the sham stimulation a specific sham-coil system was used. Fourteen patients were followed for 6 months. Treatment outcome was assessed with a specific tinnitus questionnaire (Goebel and Hiller). SETTING: Tertiary referral medical center. RESULTS: Increased metabolic activation in the auditory cortex was verified in all patients. After 5 days of verum rTMS, a highly significant improvement of the tinnitus score was found whereas the sham treatment did not show any significant changes. The treatment outcome after 6 months still demonstrated significant reduction of tinnitus score. CONCLUSION: These preliminary results demonstrate that neuronavigated rTMS offers new possibilities in the understanding and treatment of chronic tinnitus.

Transcranial magnetic stimulation for central pain.

Transcranial magnetic stimulation recently has emerged as a therapeutic tool in neurology and psychiatry, with contradictory results. Central pain, a major chronic pain syndrome affecting millions of people worldwide, has been the focus of a few studies. Although transcranial magnetic stimulation has no role in the chronic management of such pain, it has potential as a screening procedure for the much more effective extradural cortical stimulation, a minimally invasive neurosurgical procedure that has emerged as the technique of choice in treating these patients.

Transcranial magnetic stimulation accelerates the antidepressant effect of amitriptyline in severe depression: a double-blind placebo-controlled study.

BACKGROUND: Transcranial magnetic stimulation (TMS) is a noninvasive method to stimulate the cortex, and the treatment of depression is one of its potential therapeutic applications. Three recent meta analyses strongly suggest its benefits in the treatment of depression. The present study investigates whether repetitive TMS (rTMS) accelerates the onset of action and increases the therapeutic effects of amitriptyline. METHODS: Forty-six outpatients meeting DSM-IV criteria for nonpsychotic depressive episode were randomly assigned to receive rTMS (n = 22) or sham repetitive TMS (sham) (n = 24) during 4 weeks over dorsolateral prefrontal cortex (DLPFC) in this double-blind controlled trial. All patients were concomitantly taking amitriptyline (mean dose 110 mg/d). The rTMS group received 20 sessions (5 sections per week) of 5 Hz rTMS (120% of motor threshold and 1250 pulses per session). Sham stimulation followed the same schedule, however, using a sham coil. The efficacy variables were the Hamilton Depression Rating Scale-17 items (HAM-D/17), the Montgomery-Asberg Depression Rating Scale (MADRS), a Visual Analogue Scale (VAS), and the Clinical Global Impression (CGI). Tolerability was assessed by clinical examination and a safety screening of TMS side effects. RESULTS: Repetitive TMS had a significantly faster response to amitriptyline. There was a significant decrease in HAM-D/17 scores, already after the first week of treatment (p < .001 compared with baseline and p < .001 compared with sham). The decrease in HAM-D/17 scores in the rTMS group was significantly superior compared with the sham group throughout the study (p < .001 at fourth week). CONCLUSIONS: Repetitive TMS at 5 Hz accelerated the onset of action and augmented the response to amitriptyline.

Slow transcranial magnetic stimulation can rapidly reduce resistant auditory hallucinations in schizophrenia.

BACKGROUND: Almost a quarter of patients with schizophrenia present with resistant auditory verbal hallucinations (AVH), a phenomenon that may relate to activation of brain areas underlying speech perception. Repetitive transcranial magnetic stimulation (rTMS) at 1 Hz reduces cortical activation, and recent results have shown that 1-Hz left temporoparietal rTMS may reduce AVH. The aim of this study was to replicate recent data and investigate whether low-frequency rTMS with a high total stimulation number delivered in a shorter 5-day block produces similar benefit. METHODS: Ten right-handed schizophrenia patients with resistant AVH received 5 days of active rTMS and 5 days of sham rTMS (2,000 stimulations per day at 90% of motor threshold) over the left temporoparietal cortex in a double-blind crossover design. The two weeks of stimulation were separated by a 1-week washout period. RESULTS: AVH were robustly improved (56%) by 5 days active rTMS, whereas no variation was observed after sham. Seven patients were responders to active treatment, five of whom maintained improvement for at least 2 months. CONCLUSIONS: These data confirm the efficiency of low-frequency rTMS applied to the left temporoparietal cortex, compared with sham stimulation, in reducing resistant AVH. This improvement can be obtained in only 5 days without serious initial adverse events.

[Vagus nerve stimulation, repetitive transcranial magnetic stimulation, and electroconvulsive therapy in the treatment of depressive disorders]. / Antidepressive Stimulationsverfahren Vagusnervstimulation, repetitive transkranielle Magnetstimulation und Elektrokonvulsionstherapie zur Behandlung depressiver Störungen.

Affective disorders, especially major depression, are the most common psychiatric disorders. Although well treatable, a number of patients do not or do not sufficiently respond to antidepressant pharmacotherapy. Therefore there is a need for safe and efficient alternative therapeutic strategies. Neurostimulatory therapies such as electroconvulsive therapy, repetitive transcranial magnetic stimulation, and vagus nerve stimulation belong to these alternatives. In this article we review their mechanisms of action and summarize efficacy and adverse effects.

Effect of electroconvulsive therapy on cortical excitability in patients with major depression: a transcranial magnetic stimulation study.

OBJECTIVE: The antidepressant action of electro-convulsive therapy (ECT) and repetitive transcranial magnetic stimulation (rTMS) may be related to their ability to modulate cortical excitability. The aim of this study was to investigate changes in cortical excitability following ECT in patients with major depression (MD) and to compare therapeutic efficacy of ECT combined with rTMS to that of ECT alone. METHODS: Twenty-two patients with MD were assigned to receive ECT and right prefrontal 1 Hz rTMS (n=12) or ECT with sham rTMS (n=10). ECT was given twice weekly and rTMS was applied on the remaining 4 days, throughout 3 weeks. The resting motor threshold (rMT) and motor evoked potential (MEP)/M-wave area ratio were evaluated before and 6 h after the first, third and sixth ECT session. The active motor threshold (aMT), intra-cortical inhibition (ICI) and intra-cortical facilitation (ICF) were measured at baseline and 24 h after the last ECT. RESULTS: There were no significant differences in the degree of clinical improvement and measures of cortical excitability in the ECT+active rTMS group as compared to the ECT+sham rTMS group. Marked clinical improvement observed in 19 out of the 22 patients was associated with a significant increase of the MEP/M-wave area ratio, decrease of the aMT and reduction of the ICI in the left hemisphere. CONCLUSIONS: The antidepressant effect of ECT was associated with an enhancement of left hemispheric excitability. rTMS did not add to the beneficial effect of ECT. However, the small sample size and the robust effect of ECT might have obscured a potential therapeutic effect of rTMS. SIGNIFICANCE: Measures of cortical excitability may provide insight to our understanding of the mechanism of action of ECT and might be useful for the assessment of treatment response.