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

BACKGROUND: Repetitive transcranial magnetic stimulation (TMS) as a treatment for depression has shown statistically significant effects, but the clinical significance of these effects has been questioned. METHODS: Patients with medication-resistant depression were randomized to receive 15 sessions of active or sham repetitive TMS delivered to the left dorsolateral prefrontal cortex at 110% the estimated prefrontal cortex threshold. Each session consisted of 32 trains of 10 Hz repetitive TMS delivered in 5-second trains. The primary end point was treatment response defined as a >or=50% decrease in Hamilton Depression Rating Scale (HDRS) score at both 1 and 2 weeks following the final repetitive TMS treatment. Remission was defined as a HDRS score < 8. RESULTS: The response rate for the TMS group was 30.6% (11/35), significantly (p = .008) greater than the 6.1% (2/33) rate in the sham group. The remission rate for the TMS group was 20% (7/35), significantly (p = .033) greater than the 3% (1/33) rate in the sham group. The HDRS scores showed a significantly (p < .002) greater decrease over time in the TMS group compared with the sham group. CONCLUSIONS: Transcranial magnetic stimulation can produce statistically and clinically significant antidepressant effects in patients with medication-resistant major depression.     

A 3-month, follow-up, randomized, placebo-controlled study of repetitive transcranial magnetic stimulation in depression

BACKGROUND/OBJECTIVE: There is evidence for an antidepressant effect of repetitive transcranial magnetic stimulation (rTMS), but little is known about posttreatment course. Therefore, we conducted a placebo-controlled, double-blind study in depressed patients in order to investigate the effect of rTMS on depression over 12 weeks after completion of the 2-week stimulation period. METHOD: 55 patients with a moderate or severe DSM-IV major depressive episode were randomly assigned to rTMS or sham treatment. rTMS was given daily for 10 days over the left dorsolateral prefrontal cortex with the following treatment parameters: 20 Hz, 20 trains of 2 seconds, 30 seconds between trains, and 80% motor threshold. The effect of rTMS on depression was rated repeatedly with the 17-item Hamilton Rating Scale for Depression (HAM-D) during the 2-week period of stimulation and the 12-week follow-up period conducted from 1997 to 2001. RESULTS: We found a modest, clinically nonrelevant decrease in HAM-D scores in both rTMS and sham patients over 2 weeks of treatment. However, over the subsequent 12-week follow-up, the rTMS group continued to improve significantly compared with the placebo group. CONCLUSION: Decrease of depressive symptoms may continue after the cessation of rTMS stimulation.     

Augmentative repetitive navigated transcranial magnetic stimulation (rTMS) in drug-resistant bipolar depression

Objectives:  The efficacy of transcranial magnetic stimulation (TMS) has been poorly investigated in bipolar depression. The present study aimed to assess the efficacy of low-frequency repetitive TMS (rTMS) of the right dorsolateral prefrontal cortex (DLPFC) combined with brain navigation in a sample of bipolar depressed subjects.
Methods:  Eleven subjects with bipolar I or bipolar II disorder and major depressive episode who did not respond to previous pharmacological treatment were treated with three weeks of open-label rTMS at 1 Hz, 110% of motor threshold, 300 stimuli/day.
Results:  All subjects completed the trial showing a statistically significant improvement on the 21-item Hamilton Depression Rating Scale (HAM-D), Montgomery-Åsberg Depression Rating Scale, and Clinical Global Impression severity of illness scale (ANOVAs with repeated measures: F  =   22.36, p < 0.0001; F  =   12.66, p < 0.0001; and F  =   10.41, p < 0.0001, respectively). In addition, stimulation response, defined as an endpoint HAM-D score reduction of ≥50% compared to baseline, was achieved by 6 out of 11 subjects, 4 of whom were considered remitters (HAM-D endpoint score ≤ 8). Partial response (endpoint HAM-D score reduction between 25% and 50%) was achieved by 3/11 patients. No manic/hypomanic activation was detected during the treatment according to Young Mania Rating Scale scores (ANOVAs with repeated measures: F  =   0.62, p = 0.61). Side effects were slight and were limited to the first days of treatment.
Conclusions:  Augmentative low-frequency rTMS of the right DLPFC combined with brain navigation was effective and well tolerated in a small sample of drug-resistant bipolar depressive patients, even though the lack of a sham controlled group limits confidence in the results.     

Does rTMS hasten the response to escitalopram, sertraline, or venlafaxine in patients with major depressive disorder? A double-blind, randomized, sham-controlled trial

BACKGROUND/OBJECTIVE: Repetitive transcranial magnetic stimulation (rTMS) has been mainly studied as adjunctive treatment for drug-resistant patients. We assessed the effectiveness of rTMS started concomitantly with antidepressant medications in non-drug-resistant major depressive disorder patients. We also evaluated if, among the 3 antidepressants administered, one had a better synergy with rTMS. METHOD: In this 5-week, double-blind, randomized, sham-controlled study, we recruited 99 inpatients suffering from a major depressive episode (DSM-IV criteria). They were randomly assigned to receive venlafaxine, sertraline, or escitalopram in combination with a 2-week period of sham or active 15-Hz rTMS on the left dorso-lateral prefrontal cortex. Data were gathered from February 2004 to June 2005. RESULTS: The active rTMS group showed a significantly faster reduction in Hamilton Rating Scale for Depression (HAM-D) scores compared with the sham group (p = .0029). The response and remission rates were significantly greater in the active rTMS group after the stimulation period (p = .002 and p = .003, respectively), but not at the endpoint. We found no significant difference in HAM-D score reduction among the 3 drugs administered, either in the active or in the sham group. CONCLUSION: These findings support the efficacy of rTMS in hastening the response to antidepressant drugs in patients with major depressive disorder. The effect of rTMS seems to be unaffected by the specific concomitantly administered drug.     

Acute mood and thyroid stimulating hormone effects of transcranial magnetic stimulation in major depression.

BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) has recently been demonstrated to have antidepressant effects. Some work suggests that rTMS over prefrontal cortex administered to healthy individuals produces acute elevations of mood and serum thyroid-stimulating hormone (TSH). We sought to determine whether single rTMS sessions would produce acute mood and serum TSH elevations in subjects with major depressions. METHODS: Under double-blind conditions et al 14 medication-free subjects with major depression received individual sessions of either active or sham rTMS. rTMS was administered over the left prefrontal cortex at 10 Hz et al 100% of motor threshold, 20 trains over 10 min. Immediately before and after rTMS sessions, subjects' mood was rated with the Profile of Mood States (POMS) and the 6-Item Hamilton Depression Scale, and blood was drawn for later analysis of TSH. Subjects and raters were blind to treatment assignment. RESULTS: The group receiving active stimulation manifested significantly greater improvement on the POMS subscale of Depression (p < or = .0055) and a trend toward greater improvement on the modified Hamilton Rating (.05 < p < or =.1). No hypomania was induced. The change in TSH from pre- to post-rTMS was significantly different between active and sham sessions. CONCLUSIONS: This blinded, placebo-controlled trial documents that individual rTMS sessions can acutely elevate mood and stimulate TSH release in patients experiencing major depressive episodes.     

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.     

Repetitive transcranial magnetic stimulation (rTMS) in pharmacotherapy-refractory major depression: comparative study of fast, slow and sham rTMS

In previous studies, fast repetitive transcranial magnetic stimulation (rTMS) with a frequency > 1 Hz demonstrated substantial antidepressant effects compared to sham rTMS. However, it is not clear whether fast rTMS is superior to slow rTMS (frequency < or = 1 Hz) which is safe at therapeutically promising higher intensities. The aim of this double-blind study was to compare the action of fast, slow and sham rTMS. Eighteen patients with pharmacotherapy-resistant major depression were randomized to receive fast (10 Hz), slow (0.3 Hz) or sham rTMS with 250 stimuli/day for 5 successive days. rTMS was applied at 90% motor threshold intensity to the left dorsolateral prefrontal cortex. Scores on the Hamilton Depression Rating Scale (HDRS), but not on the Montgomery-Asberg Depression Rating Scale (MADRS), showed a statistically significant time x group interaction with a reduction of 19% after slow rTMS. However, the effect was clinically marginal and not reflected by self-rating scores. Verbal memory and reaction performance were not impaired after rTMS, and there was even a statistically significant time x group interaction with improvement of verbal memory performance after fast rTMS. In conclusion, this study further supported the safety of rTMS but does not show any clinically meaningful antidepressant efficacy of rTMS at 250 daily stimuli over 5 days in pharmacotherapy-refractory major depression.     

Add-on rTMS for treatment of depression: a pilot study using stereotaxic coil-navigation according to PET data

OBJECTIVE: Repetitive transcranial magnetic stimulation (rTMS) is regarded as a potentially new tool to treat depression. In a double-blind, randomized, sham-controlled pilot study we investigated the efficacy of neuronavigated rTMS, guided according to the prefrontal metabolic state determined by positron emission tomography (PET). METHODS: 25 patients with major depression were included. Prior to rTMS, PET scans were obtained. For the real stimulation condition, the dorsolateral prefrontal cortex (DLPFC) with lower metabolic activity compared to the contralateral hemisphere was selected, if detected by prior PET. Stimulation parameters were 15 Hz, 110% motor threshold (MT), 3000 stimuli/day, for 10 days. A neuronavigational system was used to place the magnetic coil above each individuals' selected cortical region (real condition: DLPFC, sham: midline parieto-occipital, intensity 90% of MT). RTMS was administered add-on to medication. Depression-related symptoms were rated with Beck's, Hamilton's (HAM-D), and Montgomery-Asberg's (MADRS) depression rating scales. RESULTS: Real stimulation improved depression according to HAM-D and MADRS moderately but significantly better compared to sham at the end of the stimulation sessions. In the real condition, four out of 13 patients responded with a mean improvement in HAM-D and/or MADRS of at least 50%, whereas none responded to sham. Antidepressant effects of stimulation of the relatively hypometabolic DLPFC were comparable to stimulation in absence of metabolic differences. CONCLUSIONS: A moderate improvement of depressive symptoms after rTMS was observed. Our preliminary data show that stimulation of prefrontal hypometabolism may not be advantageous to stimulation irrespective of the metabolic state.     

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.     

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

The majority of previous clinical studies have indicated that repetitive transcranial magnetic stimulation (rTMS) may have antidepressant effects. Herein, we investigated the longitudinal, long-term antidepressant efficacy of daily left prefrontal cortex (PFC) rTMS for a 1-week period. Nineteen patients were randomly assigned to two treatment groups at 90% of individual motor threshold (MT): Twelve received active repetitive transcranial magnetic stimulation and seven received sham treatment. Each patient underwent five sessions of twenty 2-s trains of 20 Hz rTMS with 800 stimuli/day. The Beck Depression Inventory and the Hamilton Depression Rating Scale were used to assess severity of depression at 1, 4 and 12 weeks post-therapy. A significant reduction of baseline depression scores was observed after 1 week of active treatment that lasted for 1 month, indicating improvement of depressive symptoms. No significant effects were observed in patients receiving sham treatment. The results of this controlled study are in agreement with the findings of previous studies suggesting that daily left PFC rTMS has an antidepressant effect.     

A comparative study of the effects of repetitive paired transcranial magnetic stimulation on motor cortical excitability

OBJECTIVES: Various methods of application of repetitive transcranial magnetic stimulation (TMS) have been evaluated for their potential capacity to alter motor cortical excitability. Initial research suggests that the repetitive application of paired TMS pulses (repetitive paired pulse TMS (rppTMS)) may have greater effects on cortical excitability, perhaps through the facilitation of I-wave interaction. We aimed to compare the post-train effects of 15 min trains of rppTMS to investigate the potential therapeutic application of this technique as well as to compare it to a standard high frequency repetitive TMS paradigm. METHODS: Ten normal subjects received three 15 min sessions of rppTMS, 5 Hz high frequency rTMS and sham TMS in randomised order. rppTMS consisted of a single train of 180 pulse pairs (0.2 Hz, 1.5 ms inter-stimulus interval, supra-threshold intensity) administered over 15 min. The rTMS condition involved 750 pulses provided in 5s 5 Hz trains with a 25s inter-train interval at 90% of the RMT. Motor evoked potential size and cortical silent period duration were assessed before and after each session. RESULTS: There were no significant changes in cortical excitability produced by any of the stimulation conditions. Five hertz rTMS produced an increase in cortical silent period duration (p=0.004) which was not affected by rppTMS. CONCLUSIONS: Fifteen minutes trains of 1.5ms rppTMS do not substantially increase post train cortical excitability. Repetitive brief trains of 5Hz rTMS also do not alter excitability but appear to effect cortical inhibition.     

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.     

A randomized, controlled trial with 6-month follow-up of repetitive transcranial magnetic stimulation and electroconvulsive therapy for severe depression

OBJECTIVE: Repetitive transcranial magnetic stimulation (rTMS) has been reported to be as effective as electroconvulsive therapy (ECT) for major depression. The authors conducted a multicenter randomized, controlled trial to test the equivalence of rTMS with ECT. METHOD: Forty-six patients with major depression referred for ECT were randomly assigned to either a 15-day course of rTMS of the left dorsolateral prefrontal cortex (N=24) or a standard course of ECT (N=22). The primary outcome measures were the score on the 17-item Hamilton Depression Rating Scale (HAM-D) and the proportion of patients with remissions (Hamilton score, 相似文献   

The effects of repetitive transcranial magnetic stimulation on depressive symptoms and the P(300) event-related potential

Changes in the Hamilton Depression Rating Scale and the P(300) auditory event-related potential were assessed in 10 patients with depression before and after a treatment course of five daily sessions of 10 Hz repetitive transcranial magnetic stimulation (rTMS) over the left prefrontal cortex. The patients were initially randomly allocated either to an active or a placebo rTMS treatment. All patients received both types of treatment separated by an interval of 4 weeks. The median Hamilton score decreased by 7 points following active rTMS and by 1 point after sham (p=0.075). Active rTMS was associated with a significant increase in the P(300) amplitude compared with sham (p=0.02). There was no correlation between changes in P(300) measurements and the Hamilton scores after active treatment. We conclude that five daily sessions of left prefrontal rTMS treatment is not of sufficient duration to make a significant improvement in depressive symptoms.     

Bilateral prefrontal rTMS and theta burst TMS as an add-on treatment for depression: A randomized placebo controlled trial

Objectives. Repetitive transcranial magnetic stimulation (rTMS) of the left dorsolateral-prefrontal cortex (DLPFC) exerts antidepressant effects. In this randomised controlled clinical trial we aimed to test the safety and therapeutic efficacy of bilateral theta-burst stimulation (TBS) as an add-on therapy to standard treatment of major depression. Methods. Fifty-six patients diagnosed with a moderate to severe depressive episode received 15 daily treatments of either rTMS (110% motor-threshold; rightDLPFC, 1000 stimuli at 1 Hz + leftDLPFC, 1000 stimuli at 10 Hz), theta-burst stimulation (80% motor-threshold; rightDLPFC, continuous TBS, 1200 stimuli + leftDLPFC, intermittent TBS, 1200 stimuli), or sham TMS (N = 17, sham coil with the TBS protocol). Results. There was no significant effect in the primary outcome measures (change of the 21-item Hamilton Rating Scale for Depression). However, there was a tendency towards an increased responder rate at the end of the follow-up period for both active treatments as compared to sham, and this tendency was most pronounced for the TBS group. Conclusions. This pilot study did not reveal significant advantages of bilateral TBS or rTMS over sham treatment as an add-on treatment for major depression. A tendency towards a superior effect of bilateral TBS at the end of the follow-up period may warrant further studies.     

Repetitive transcranial magnetic stimulation versus electroconvulsive therapy for major depression: preliminary results of a randomized trial.

BACKGROUND: Many severely depressed patients do not benefit from or tolerate existing treatments. Repetitive transcranial magnetic stimulation (rTMS) has been reported to benefit depression. We compared rTMS to electroconvulsive therapy (ECT) in severely ill, depressed patients. METHODS: Twenty-five patients with a major depression (unipolar or bipolar) deemed clinically appropriate for ECT were randomly assigned to rTMS (10-20 treatments, 10 Hz, 110% motor threshold applied to the left dorsolateral prefrontal cortex for a total of 10,000-20,000 stimulations) or a course of bitemporal ECT (4-12 treatments). The primary outcome measure was the 24-item Hamilton Depression Rating Scale (HDRS). The Brief Psychiatric Rating Scale (BPRS), Young Mania Rating Scale (YMS), and Clinical Global Impression scale (CGI) were secondary measures. Minimal rescue medications were utilized. RESULTS: Mean percent improvement on the baseline HDRS score did not significantly differ between the two treatments (i.e., 55% for the rTMS group vs. 64% for the ECT group [p = ns]). With response defined as a 50% reduction from baseline and a final score < or = 8 on the HDRS, there was also no significant difference between the two groups. We did not observe any differences between groups on the secondary measures. CONCLUSIONS: A 2-4 week randomized, prospective trial comparing rTMS to ECT produced comparable therapeutic effects in severely depressed patients.     

Comparison of monophasic versus biphasic stimulation in rTMS over premotor cortex: SEP and SPECT studies

OBJECTIVE: To optimize the clinical uses of repetitive transcranial magnetic stimulation (rTMS), we compared the effects of rTMS on somatosensory-evoked potentials (SEPs) and regional cerebral blood flow (rCBF) using different phases (monophasic vs. biphasic) or frequencies (0.2Hz vs. 0.8Hz) of stimulation. METHODS: In the first experiment, different phases were compared (0.2Hz monophasic vs. 0.2Hz biphasic). Biphasic 1Hz or sham condition served as controls. The second experiment was to explore the effect of frequencies (0.2Hz vs. 0.8Hz) using the monophasic stimulation. Substhreshold TMS was applied 250 times over the left premotor cortex. Single photon emission computed tomography (SPECT) was performed before and after monophasic 0.2Hz or biphasic 1Hz rTMS. RESULTS: Monophasic rTMS of both 0.2 and 0.8Hz significantly increased the ratio of N30 amplitudes as compared with sham rTMS, whereas biphasic stimulation showed no significant effects. SPECT showed increased rCBF in motor cortices after monophasic 0.2Hz rTMS, but not after biphasic 1Hz stimulation. CONCLUSIONS: Monophasic rTMS exerted more profound effects on SEPs and rCBF than biphasic rTMS over the premotor cortex. SIGNIFICANCE: Monophasic rTMS over the premotor cortex could be clinically more useful than biphasic rTMS.     

Repetitive transcranial magnetic stimulation of the dorsolateral prefrontal cortex affects divided attention immediately after cessation of stimulation

Transcranial magnetic stimulation has evolved into a powerful neuroscientific tool allowing to interfere transiently with specific brain functions. In addition, repetitive TMS (rTMS) has long-term effects (e.g. on mood), probably mediated by neurochemical alterations. While long-term safety of rTMS with regard to cognitive functioning is well established from trials exploring its therapeutic efficacy, little is known on whether rTMS can induce changes in cognitive functioning in a time window ranging from minutes to hours, a time in which neurochemical effects correlated with stimulation have been demonstrated. This study examined effects of rTMS on three measures of executive function in healthy subjects who received one single rTMS session (40 trains of 2 s duration 20 Hz stimuli) at the left dorsolateral prefrontal cortex (DLPFC). Compared to a sham condition one week apart, divided attention performance was significantly impaired about 30-60 min after rTMS, while Stroop-interference and performance in the Wisconsin Card Sorting Test was unaffected after rTMS. Repetitive TMS of the left DLPFC, at stimulation parameters used in therapeutic studies, does not lead to a clinically relevant impairment of executive function after stimulation. However, the significant effect on divided attention suggests that cognitive effects of rTMS are not limited to the of acute stimulation, and may possibly reflect known neurochemical alterations induced by rTMS. Sensitive cognitive measures may be useful to trace those short-term effects of rTMS non-invasively in humans.     

Identifying brain imaging correlates of clinical response to repetitive transcranial magnetic stimulation (rTMS) in major depression

BackgroundPartial response and non-response to treatments are common problems in major depression. The identification of biological markers of clinical response may be of special interest for some adjunctive treatments, such as repetitive transcranial magnetic stimulation (rTMS), as it may ultimately improve their cost-effectiveness.ObjectiveTo identify pre-treatment functional imaging correlates of clinical response to rTMS in major depression.MethodsWe evaluated 21 depressed patients. They were randomized to receive 15 sessions of active or sham rTMS on the left dorsolateral prefrontal cortex. Functional magnetic resonance imaging (fMRI) was used to assess pre-treatment regional brain activity evoked by a word generation task. These regional activations were correlated (voxel-wise) with the Hamilton Rating Scale for Depression (HAM-D) reduction between baseline and end of treatment. A group of 13 healthy controls was also assessed using the same fMRI protocol to obtain reference imaging measurements.ResultsAt the end of treatment, the percentage of patients with a HAM-D reduction greater than 50% was larger in the active than in the sham rTMS group (70% vs. 27.3%). In the active rTMS group, larger HAM-D reductions were significantly correlated with smaller deactivations during pre-treatment fMRI assessment in the anterior cingulate, the left medial orbitofrontal and the right middle frontal cortices, in addition to larger activations in the left ventral-caudal putamen.ConclusionsThese results suggest that brain activity in regions arguably relevant for major depression may predict clinical response to rTMS. This approach may help in identifying the most suitable candidates to undergo rTMS treatment.     

Efficacy and safety of transcranial magnetic stimulation in the acute treatment of major depression: a multisite randomized controlled trial.

BACKGROUND: We tested whether transcranial magnetic stimulation (TMS) over the left dorsolateral prefrontal cortex (DLPFC) is effective and safe in the acute treatment of major depression. METHODS: In a double-blind, multisite study, 301 medication-free patients with major depression who had not benefited from prior treatment were randomized to active (n = 155) or sham TMS (n = 146) conditions. Sessions were conducted five times per week with TMS at 10 pulses/sec, 120% of motor threshold, 3000 pulses/session, for 4-6 weeks. Primary outcome was the symptom score change as assessed at week 4 with the Montgomery-Asberg Depression Rating Scale (MADRS). Secondary outcomes included changes on the 17- and 24-item Hamilton Depression Rating Scale (HAMD) and response and remission rates with the MADRS and HAMD. RESULTS: Active TMS was significantly superior to sham TMS on the MADRS at week 4 (with a post hoc correction for inequality in symptom severity between groups at baseline), as well as on the HAMD17 and HAMD24 scales at weeks 4 and 6. Response rates were significantly higher with active TMS on all three scales at weeks 4 and 6. Remission rates were approximately twofold higher with active TMS at week 6 and significant on the MADRS and HAMD24 scales (but not the HAMD17 scale). Active TMS was well tolerated with a low dropout rate for adverse events (4.5%) that were generally mild and limited to transient scalp discomfort or pain. CONCLUSIONS: Transcranial magnetic stimulation was effective in treating major depression with minimal side effects reported. It offers clinicians a novel alternative for the treatment of this disorder.