Effects of repetitive transcranial magnetic stimulation in subjects with sleep disorders

In this review, we aimed at identifying the studies that have employed repetitive transcranial magnetic stimulation (rTMS) in patients with sleep disorders. Low-frequency (LF) rTMS stimulating the right dorsolateral prefrontal cortex (DLPFC) or the posterior parietal cortex (PPC) was found to be effective to reduce cortical hyperexcitability and improve the sleep quality in subjects with chronic primary insomnia (PI). Both high-frequency (HF) and LF rTMS applied over the primary motor cortex or the supplementary motor cortex seem to have transient beneficial effects in patients with restless legs syndrome (RLS). Stimulation of upper airway muscles during sleep by isolated TMS and by rTMS twitch can improve airflow dynamics in obstructive sleep apnea syndrome (OSAS) patients without arousal. A single case report study indicates that HF rTMS over the left DLPFC might represent an alternative choice for symptom control in narcoleptic patients with cataplexy, and a pilot study also raises the possibility of therapeutic benefits from rTMS in patients with sleep bruxism. rTMS may also exert intrinsic effects on hypersomnia in depressed adolescents.In conclusion, rTMS may contribute to the development of new non-pharmacological therapeutic options for several sleep disorders. rTMS might be useful as therapeutical tool in particular in patients with PI, RLS, OSAS and narcolepsy, while its effect in other sleep disorders (ie, parasomnias) has not yet been explored. rTMS integrated with clinical, sleep-related, and neuroimaging data may represent an effective tool in modulating cortical excitability and inducing short-term synaptic plasticity. Further studies with larger patient samples, repeated sessions, an optimized rTMS setup, and clinical follow-up warranted to verify the initial findings, and to expand clinical and research interest towards neuromodulation in the different sleep disorders.     

Impaired short-term plasticity in restless legs syndrome: a pilot rTMS study

BackgroundPrevious studies showed an impairment of the LTP-like plasticity to TMS in restless legs syndrome (RLS). Clinically, repetitive TMS (rTMS) was effective in alleviating the sensory-motor complaints of patients, although the effects induced by low-frequency (inhibitory) rTMS have not yet been investigated. An impaired LTD-like mechanism of cortical plasticity has been hypothesized, which we have directly assessed in this pilot study.MethodsMotor evoked potentials (MEPs) from the right first dorsal interosseus muscle were recorded at the stimulus intensity of 110% of the resting motor threshold (rMT) from 13 right-handed patients and ten age-matched right-handed healthy controls. Median peak-to-peak amplitudes were calculated in all participants at baseline (T₀), after the first train of a single evening session of low-frequency (1 Hz) rTMS over the left primary motor cortex (T₁), and after the whole rTMS procedure (T₂), which consists of 20 trains with 50 stimuli per train and intertrain interval of 30 s (1000 stimuli in total).ResultsNo differences were found for rMT and MEPs size between the two groups at T₀. Smaller MEPs amplitudes at both T₁ and T₂ were observed in all subjects, although this was significantly more pronounced in controls than in patients.ConclusionsCompared to normal individuals, patients exhibited an impairment of the LTD-like mechanisms induced by inhibitory rTMS, thus adding support to the involvement of GABA in RLS pathophysiology. Although future studies with a larger population are needed, TMS is confirmed to be effective in noninvasive probing of the neurophysiology and neurochemistry of RLS.     

Transcranial magnetic stimulation studies in complex regional pain syndrome type I: A review

The sensory and motor cortical representation corresponding to the affected limb is altered in patients with complex regional pain syndrome (CRPS). Transcranial magnetic stimulation (TMS) represents a useful non‐invasive approach for studying cortical physiology. If delivered repetitively, TMS can also modulate cortical excitability and induce long‐lasting neuroplastic changes. In this review, we performed a systematic search of all studies using TMS to explore cortical excitability/plasticity and repetitive TMS (rTMS) for the treatment of CRPS. Literature searches were conducted using PubMed and EMBASE. We identified 8 articles matching the inclusion criteria. One hundred fourteen patients (76 females and 38 males) were included in these studies. Most of them have applied TMS in order to physiologically characterize CRPS type I. Changes in motor cortex excitability and brain mapping have been reported in CRPS‐I patients. Sensory and motor hyperexcitability are in the most studies bilateral and likely involve corresponding regions within the central nervous system rather than the entire hemisphere. Conversely, sensorimotor integration and plasticity were found to be normal in CRPS‐I. TMS examinations also revealed that the nature of motor dysfunction in CRPS‐I patients differs from that observed in patients with functional movement disorders, limb immobilization, or idiopathic dystonia. TMS studies may thus lead to the implementation of correct rehabilitation strategies in CRPS‐I patients. Two studies have begun to therapeutically use rTMS. This non‐invasive brain stimulation technique could have therapeutic utility in CRPS, but further well‐designed studies are needed to corroborate initial findings.     

A randomized controlled comparison of electroconvulsive therapy and repetitive transcranial magnetic stimulation in severe and resistant nonpsychotic major depression.

BACKGROUND: Studies published over the past few years suggest that transcranial magnetic stimulation (TMS) may have significant antidepressant actions. In a previous report, we compared electroconvulsive therapy (ECT) and repetitive TMS (rTMS) and found ECT to be superior for psychotic major depression (MD); however, ECT and rTMS had similar results in nonpsychotic MD. We now report on a controlled randomized comparison of ECT and rTMS in patients with nonpsychotic MD. METHODS: Forty patients with nonpsychotic MD referred for ECT were included. Electroconvulsive therapy was performed according to established protocols. Repetitive TMS was performed over the left dorsolateral prefrontal cortex at 90% motor threshold. Patients were treated with 20 sessions (five times per week for 4 weeks) of 10-Hz treatments (1200 pulses per treatment-day) at 90% motor threshold. Response to treatment was defined as a decrease of at least 50% in the Hamilton Rating Scale for Depression (HRSD) score, with a final HRSD equal or less than 10 points and a final Global Assessment of Function Scale rating of 60 or more points. RESULTS: The overall response rate was 58% (23 out of 40 patients responded to treatment). In the ECT group, 12 responded and eight did not; in the rTMS group, 11 responded and nine did not (chi2 =.10, ns). Thus, patients responded as well to either ECT or rTMS. CONCLUSIONS: This study adds to the growing literature supporting an antidepressant effect for rTMS. This study is particularly relevant because it suggests that rTMS and ECT reach similar results in nonpsychotic major depressive disorder.     

Dopamine agonists restore cortical plasticity in patients with idiopathic restless legs syndrome

In the present work, we aimed at assessing whether patients with idiopathic restless legs syndrome (RLS) showed alterations of sensory‐motor plasticity, an indirect probe for motor learning, within the motor cortex (M1). Previous findings suggest that learning in human M1 occurs through LTP‐like mechanisms. To test our hypothesis, we employed the paired associative stimulation (PAS) protocol by transcranial magnetic stimulation (TMS), which is able to induce LTP‐like effects in the motor cortex of normal subjects. Twelve patients with idiopathic RLS and 10 age‐ and sex‐matched control subjects were recruited. PAS protocol consisted of 0.05 Hz electrical median nerve stimulation (90 stimuli), paired with 0.05 Hz TMS (90 stimuli) over the hot spot for stimulating the abductor pollicis brevis (APB) muscle given 25 milliseconds after the onset of the electrical stimulus. Corticospinal excitability recorded in APB muscle, as indexed by MEP obtained after single stimulus, was tested before and up to 30 minutes after PAS protocol. Eight of 12 patients were studied before and after 4 weeks of dopaminergic treatment. PAS protocol increased significantly corticospinal excitability as long as 30 minutes in healthy subjects. On the contrary, PAS protocol did not change the amplitude of MEPs in patients with idiopathic RLS without treatment. PAS associative plasticity was restored after 4 weeks of dopaminergic treatment. Our data demonstrated that associative sensory‐motor plasticity, an indirect probe for motor learning, is impaired in idiopathic RLS patients but may be reverted to normal after dopaminergic treatment. © 2008 Movement Disorder Society     

Transcranial magnetic stimulation in hereditary ataxias: Diagnostic utility,pathophysiological insight and treatment

Transcranial magnetic stimulation (TMS) is a valuable technique to assess and modulate human brain function in normal and pathological conditions. This critical review surveys the contributions of TMS to the diagnosis, insight into pathophysiology and treatment of genetically confirmed hereditary ataxias, a heterogeneous group of neurodegenerative disorders that can affect motor cortex and the corticospinal tract. Most studies were conducted on small sample sizes and focused on diagnostic approaches. The available data demonstrate early involvement of the corticospinal tract and motor cortex circuitry, and support the possible efficacy of cerebellar repetitive TMS (rTMS) as therapeutic approach. Further TMS-based studies are warranted, to establish biomarkers for early diagnosis and disease monitoring, explore the involvement of the cerebello-dentato-thalamo-cortical projection, study the effects of rTMS-induced plasticity, and utilize rTMS for treatment.     

Cabergoline reverses cortical hyperexcitability in patients with restless legs syndrome

OBJECTIVE: To reverse the profile of abnormal intracortical excitability in patients with restless legs syndrome (RLS) by administering the dopaminergic agonist cabergoline. METHODS: The effects of this drug on motor cortex excitability were examined with a range of transcranial magnetic stimulation (TMS) protocols before and after administration of cabergoline over a period of 4 weeks in 14 patients with RLS and in 15 healthy volunteers. Measures of cortical excitability included central motor conduction time; resting and active motor threshold to TMS; duration of the cortical silent period; short latency intracortical inhibition (SICI) and intracortical facilitation using a paired-pulse TMS technique. RESULTS: Short latency intracortical inhibition was significantly reduced in RLS patients compared with the controls and this abnormal profile was reversed by treatment with cabergoline; the other TMS parameters did not differ significantly from the controls and remained unaffected after treatment with cabergoline. Cabergoline had no effect on cortical excitability of the normal subjects. CONCLUSIONS: As dopaminergic drugs are known to increase SICI, our findings suggest that RLS may be caused by a central nervous system dopaminergic dysfunction. This study demonstrates that the cortical hyperexcitability of RLS is reversed by cabergoline, and provides physiological evidence that this dopamine agonist may be a potentially efficacious option for the treatment of RLS.     

Cortical and subcortical brain effects of transcranial magnetic stimulation (TMS)-induced movement: an interleaved TMS/functional magnetic resonance imaging study.

BACKGROUND: To date, interleaved transcranial magnetic stimulation and functional magnetic resonance imaging (TMS/fMRI) studies of motor activation have not recorded whole brain patterns. We hypothesized that TMS would activate known motor circuitry with some additional regions plus some areas dropping out. METHODS: We used interleaved TMS/fMRI (11 subjects, three scans each) to elucidate whole brain activation patterns from 1-Hz TMS over left primary motor cortex. RESULTS: Both TMS (110% motor threshold) and volitional movement of the same muscles excited by TMS caused blood oxygen level-dependent (BOLD) patterns encompassing known motor circuitry. Additional activation was observed bilaterally in superior temporal auditory areas. Decreases in BOLD signal with unexpected post-task "rebounds" were observed for both tasks in the right motor area, right superior parietal lobe, and in occipital regions. Paired t test of parametric contrast maps failed to detect significant differences between TMS- and volition-induced effects. Differences were detectable, however, in primary data time-intensity profiles. CONCLUSIONS: Using this interleaved TMS/fMRI technique, TMS over primary motor cortex produces a whole brain pattern of BOLD activation similar to known motor circuitry, without detectable differences from mimicked volitional movement. Some differences may exist between time courses of BOLD intensity during TMS circuit activation and volitional circuit activation.     

Impact of 5‐Hz rTMS over the primary sensory cortex is related to white matter volume in individuals with chronic stroke

Repetitive transcranial magnetic stimulation (rTMS) is a non‐invasive brain stimulation technique that may facilitate mechanisms of motor learning. In a recent single‐blind, pseudo‐randomized study, we showed that 5‐Hz rTMS over ipsilesional primary somatosensory cortex followed by practice of a skilled motor task enhanced motor learning compared with sham rTMS + practice in individuals with chronic stroke. However, the beneficial effect of stimulation was inconsistent. The current study examined how differences in sensorimotor cortex morphology might predict rTMS‐related improvements in motor learning in these individuals. High‐resolution T1‐weighted magnetic resonance images were acquired and processed in FreeSurfer using a newly developed automated, whole brain parcellation technique. Gray matter and white matter volumes of the ipsilesional primary somatosensory and motor cortices were extracted. A significant positive association was observed between the volume of white matter in the primary somatosensory cortex and motor learning‐related change, exclusively in the group that received active 5‐Hz rTMS. A regression model with age, gray matter and white matter volumes as predictors was significant for predicting motor learning‐related change in individuals who received active TMS. White matter volume predicted the greatest amount of variance (47.6%). The same model was non‐significant when volumes of the primary motor cortex were considered. We conclude that white matter volume in the cortex underlying the TMS coil may be a novel predictor for behavioral response to 5‐Hz rTMS over the ipsilesional primary somatosensory followed by motor practice.     

Interhemispheric effects of high and low frequency rTMS in healthy humans.

OBJECTIVE: We investigated whether repetitive transcranial magnetic stimulation (rTMS) applied to the right motor cortex modified the excitability of the unstimulated left motor cortex. METHODS: Interhemispheric effects of 0.5 and 5 Hz subthreshold rTMS over the right motor cortex were examined by single pulse and paired pulse TMS and by transcranial electrical stimulation (TES) applied to the unstimulated left motor cortex. The effects of (a) 1800 pulses real and sham rTMS with 5 Hz, (b) 180 pulses real and sham rTMS with 0.5 Hz and (c) 1800 pulses real rTMS with 0.5 Hz were studied. RESULTS: Following 5 Hz right motor rTMS motor evoked potential (MEP) amplitudes induced by single pulse TMS over the left motor cortex increased significantly. Intracortical inhibition (ICI) and facilitation (ICF) and MEP amplitudes evoked by TES were unchanged. Sham stimulation had no influence on motor cortex excitability. After 180 pulses right motor cortex rTMS with 0.5 Hz a significant decrease of left motor ICF, but no change in single pulse MEP amplitudes was found. A similar trend was observed with 1800 pulses rTMS with 0.5 Hz. CONCLUSIONS: High frequency right motor rTMS can increase left motor cortex excitability whereas low frequency right motor rTMS can decrease it. These effects outlast the rTMS by several minutes. The underlying mechanisms mediating interhemispheric excitability changes are likely to be frequency dependent.     

Mechanisms underlying mirror movements in Parkinson's disease: a transcranial magnetic stimulation study.

The neural mechanisms underlying unintended mirror movements (MMs) of one hand during unimanual movements of the other hand in patients with Parkinson's disease (PD) are largely unexplored. Here we used surface electromyographic (EMG) analysis and focal transcranial magnetic stimulation (TMS) to investigate the pathophysiological substrate of MMs in four PD patients. Surface EMG was recorded from both abductor pollicis brevis (APB) and first dorsal interosseous (FDI) muscles. Cross-correlation EMG analysis revealed no common motor drive to the two APBs during intended unimanual tasks. Focal TMS of either primary motor cortex (M1) elicited normal motor-evoked potentials (MEPs) in the contralateral APB, whereas MEPs were not seen in the ipsilateral hand. During either mirror or voluntary APB contraction, focal TMS of the contralateral M1 produced a long-lasting silent period (SP), whereas stimulation of the ipsilateral M1 produced a short-lasting SP. During either mirror or voluntary finger tapping, 5 Hz repetitive TMS (rTMS) of the contralateral M1 disrupted EMG activity in the target FDI, whereas the effects of rTMS of the ipsilateral M1 were by far slighter. During either mirror or voluntary APB contraction, paired-pulse TMS showed a reduction of short-interval intracortical inhibition in the contralateral M1. These findings provide converging evidence that, in PD, MMs do not depend on unmasking of ipsilateral projections but are explained by motor output along the crossed corticospinal projection from the mirror M1.     

Effects of rTMS on grip force control following subcortical stroke

Within the concept of interhemispheric competition we tested the effect of inhibitory 1 Hz repetitive transcranial magnetic stimulation (rTMS), applied over the primary motor cortex of the unaffected hemisphere, upon dexterity of the affected hand in subcortical stroke patients. Subjects grasped, lifted and held an instrumented object between the index finger and thumb with both the affected and unaffected hand prior to (baseline) and following 1 Hz rTMS applied over (i) the vertex (control stimulation) and (ii) the primary motor cortex of the unaffected hemisphere. Compared to baseline, 1 Hz rTMS applied over the unaffected primary motor cortex, but not the vertex, improved the efficiency and timing of grasping and lifting with the affected hand. Our data support the interhemispheric competition concept and furthermore reinforce current efforts to implement rTMS in novel approaches to stroke rehabilitation.     

High-frequency repetitive transcranial magnetic stimulation over the hand area of the primary motor cortex disturbs predictive grip force scaling

When we repetitively lift an object, our grip force is influenced by the mechanical object properties of the preceding lift, irrespective of whether the subsequent lift is performed with the same hand or the hand opposite to the preceding lift. This study investigates if repetitive high-frequency transcranial magnetic stimulation (rTMS) over the dominant primary motor cortex affects this relationship. After completion of 10 lifts of an object using the dominant hand, rTMS was applied over the dominant primary motor cortex for 20 s. On the first lift following rTMS, the peak grip force was significantly higher than on the lift preceding rTMS. Moreover, this measure remained elevated throughout the following set of lifts after rTMS. rTMS did not change the peak lift force generated by more proximal arm muscles. The same effect was observed when the lifts following rTMS over the dominant motor cortex were performed with the ipsilateral hand. These effects were not observed when subjects rested both hands on their lap or when a sham stimulation was applied for the same period of time. These preliminary data suggest that rTMS over the sensorimotor cortex disturbs predictive grip force planning.     

Depressed intracortical inhibition after long trains of subthreshold repetitive magnetic stimuli at low frequency

OBJECTIVE: Repetitive transcranial magnetic stimulation (rTMS) modulates cortical excitability. These effects outlast the rTMS train, and range from inhibition to facilitation according to the variables used for rTMS. Several studies have demonstrated short and long-term effects on motor evoked potential (MEP) size, whereas the effects on intracortical inhibition (ICI) and facilitation (ICF) are still unclear. We investigated short- (1-15 min), intermediate- (16-30 min), and long-term (6 h) effects on intracortical excitability. METHODS: Fourteen healthy subjects were stimulated with rTMS trains of 900 pulses (1 Hz, 90% resting motor threshold (rMTh)), delivered over the primary motor cortex and the occipital area. MTh, MEP size, silent period, intracortical inhibition at short (ICI) and long inter-stimulus intervals, and ICF were tested before and after rTMS. RESULTS: ICI was reduced 16-30 min after 1 Hz rTMS trains over the primary motor area, whereas the other response variables remained unchanged. The ICI reduction at 16-30 min was reproducible on different days in the same subjects; it was absent at 6 h and after stimulation of the occipital area. CONCLUSIONS: Subthreshold 1 Hz rTMS decreases ICI by reducing the excitability of intracortical inhibitory interneurones or by altering the electrical properties of the facilitatory chain of neurons responsible for the I waves.     

Dissociating the role of prefrontal and premotor cortices in controlling inhibitory mechanisms during motor preparation

Top-down control processes are critical to select goal-directed actions in flexible environments. In humans, these processes include two inhibitory mechanisms that operate during response selection: one is involved in solving a competition between different response options, the other ensures that a selected response is initiated in a timely manner. Here, we evaluated the role of dorsal premotor cortex (PMd) and lateral prefrontal cortex (LPF) of healthy subjects in these two forms of inhibition by using an innovative transcranial magnetic stimulation (TMS) protocol combining repetitive TMS (rTMS) over PMd or LPF and a single pulse TMS (sTMS) over primary motor cortex (M1). sTMS over M1 allowed us to assess inhibitory changes in corticospinal excitability, while rTMS was used to produce transient disruption of PMd or LPF. We found that rTMS over LPF reduces inhibition associated with competition resolution, whereas rTMS over PMd decreases inhibition associated with response impulse control. These results emphasize the dissociable contributions of these two frontal regions to inhibitory control during motor preparation. The association of LPF with competition resolution is consistent with the role of this area in relatively abstract aspects of control related to goal maintenance, ensuring that the appropriate response is selected in a variable context. In contrast, the association of PMd with impulse control is consistent with the role of this area in more specific processes related to motor preparation and initiation.     

Acute left prefrontal transcranial magnetic stimulation in depressed patients is associated with immediately increased activity in prefrontal cortical as well as subcortical regions

Background

Focal prefrontal cortex repetitive transcranial magnetic stimulation (rTMS) was originally investigated as a potential antidepressant under the assumption that in depressed patients, prefrontal cortex stimulation would produce changes in connected limbic regions involved in mood regulation.

Methods

Fourteen adult patients with depression were scanned in a 1.5-T scanner using interleaved rTMS (1 Hz) applied on the left prefrontal cortex over 7.35 min. Images were analyzed with Statistical Parametric Mapping 2b and principal component analysis.

Results

Over the left prefrontal cortex, 1-Hz TMS was associated with increased activity at the site of stimulation as well as in connected limbic regions: bilateral middle prefrontal cortex, right orbital frontal cortex, left hippocampus, mediodorsal nucleus of the thalamus, bilateral putamen, pulvinar, and insula (t = 3.85, p < .001). Significant deactivation was found in the right ventromedial frontal cortex.

Conclusions

In depressed patients, 1-Hz TMS at 100% motor threshold over the left prefrontal cortex induces activation underneath the coil, activates frontal-subcortical neuronal circuits, and decreases activity in the right ventromedial cortex. Further work is needed to understand whether these immediate changes vary as a function of TMS use parameters (intensity, frequency, location) and whether they relate to neurobiologic effects and antidepressant mechanisms of TMS.     

Left prefrontal transcranial magnetic stimulation (TMS) treatment of depression in bipolar affective disorder: a pilot study of acute safety and efficacy

Objectives:  Repetitive transcranial magnetic stimulation (rTMS) has been shown to improve depressive symptoms. We designed and carried out the following left prefrontal rTMS study to determine the safety, feasibility, and potential efficacy of using TMS to treat the depressive symptoms of bipolar affective disorder (BPAD).
Methods:  We recruited and enrolled 23 depressed BPAD patients (12 BPI depressed state, nine BPII depressed state, two BPI mixed state). Patients were randomly assigned to receive either daily left prefrontal rTMS (5 Hz, 110% motor threshold, 8 sec on, 22 sec off, over 20 min) or placebo each weekday morning for 2 weeks. Motor threshold and subjective rating scales were obtained daily, and blinded Hamilton Rating Scale for Depression (HRSD) and Young Mania Rating Scales (YMRS) were obtained weekly.
Results:  Stimulation was well tolerated with no significant adverse events and with no induction of mania. We failed to find a statistically significant difference between the two groups in the number of antidepressant responders (>50% decline in HRSD or HRSD <10 – 4 active and 4 sham) or the mean HRSD change from baseline over the 2 weeks ( t =−0.22, p=0.83). Active rTMS, compared with sham rTMS, produced a trend but not statistically significant greater improvement in daily subjective mood ratings post-treatment ( t =1.58, p=0.13). The motor threshold did not significantly change after 2 weeks of active treatment ( t =1.11, p=0.28).
Conclusions:  Daily left prefrontal rTMS appears safe in depressed BPAD subjects, and the risk of inducing mania in BPAD subjects on medications is small. We failed to find statistically significant TMS clinical antidepressant effects greater than sham. Further studies are needed to fully investigate the potential role, if any, of TMS in BPAD depression.     

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.     

THETA‐BURST STIMULATION: A NEW FORM OF TMS TREATMENT FOR DEPRESSION?

Major depressive disorder (MDD) is a common debilitating condition where only one third of patients achieve remission after the first antidepressant treatment. Inadequate efficacy and adverse effects of current treatment strategies call for more effective and tolerable treatment options. Transcranial magnetic stimulation (TMS) is a noninvasive approach to manipulate brain activity and alter cortical excitability. There has been more than 15 years of research on the use of repetitive form of TMS (rTMS) for the treatment of patients with depression, which has shown it to be an effective antidepressant treatment. Even though rTMS treatment has shown efficacy in treating depression, there is a high degree of interindividual variability in response. A newer form of rTMS protocol, known as theta‐burst stimulation (TBS), has been shown to produce similar if not greater effects on brain activity than standard rTMS. TBS protocols have a major advantage over standard rTMS approaches in their reduced administration duration. Conventional rTMS procedures last between 20 and 45 min, as compared to TBS paradigms that require 1 to 3 min of stimulation. Recently, a small number of studies have suggested that TBS has similar or better efficacy in treating depression compared to rTMS. Optimization, identification of response predictors, and clarification of neurobiological mechanisms of TBS is required if it is to be further developed as a less time intensive, safe, and effective treatment for MDD.