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.     

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.     

Repetitive transcranial magnetic stimulation (rTMS) in combination with escitalopram in patients with treatment-resistant major depression: a double-blind, randomised, sham-controlled trial

BACKGROUND: The role of high-frequency rTMS over the left cortex as an add-on strategy in the treatment of major depression is still uncertain even in patients resistant to pharmacotherapy. We had planned a large sham TMS controlled study in the acute phase with a placebo-controlled relapse-prevention phase with escitalopram. However, because a recent meta-analysis showed only a small effect size of rTMS over sham TMS in the acute treatment phase of depressed patients, we decided to make an interim analysis. METHOD: In patients with medication-resistant major depression we administered in a randomised trial 15 sessions of sham-controlled rTMS over three weeks in combination with 20 mg escitalopram daily. After the last rTMS, the patients were followed for another 9 weeks on 20 mg escitalopram daily. The antidepressant effect was measured by the HAM-D(6) as primary outcome scale. RESULTS: A total of 45 patients with complete data were randomised so that 23 patients received sham TMS and 22 patients received active, high-frequency rTMS over the left cortex. Over the 3 weeks, the active rTMS treatment was superior to sham TMS with effect sizes on the HAM-D(6) above 0.70, which indicates not only a statistically but also a clinically significant effect. The patients had typically been through two failed antidepressant treatment attempts with non-tricyclics before inclusion in the study. Both the rTMS and escitalopram were well-tolerated. CONCLUSION: High-frequency rTMS over the left cortex is an add-on strategy of clinical significance in combination with escitalopram in patients with major depression resistant to non-tricyclic antidepressants.     

The effects of repetitive transcranial magnetic stimulation on depressive symptoms and the P300 event-related potential

Changes in the Hamilton Depression Rating Scale and the P₃₀₀ 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 P₃₀₀ amplitude compared with sham (p=0.02). There was no correlation between changes in P₃₀₀ 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.     

Add-on rTMS for medication-resistant depression: a randomized, double-blind, sham-controlled trial in Chinese patients

BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) has been developed as a novel tool for improving depression by delivering magnetic stimulation to the brain. However, the apparent effects of rTMS on depression have been varied in different studies. The aims of this study were to determine whether left dorsolateral prefrontal cortex rTMS can alleviate medication-resistant depression in Chinese patients and to investigate what demographic variables or clinical features may predict better response. METHOD: We designed a 2-week randomized, double-blind, sham-controlled study of add-on rTMS. A total of 30 medication-resistant patients with DSM-IV major depressive disorder or bipolar disorder, depressed episode completed 10 sessions of active or sham rTMS-10 patients at each of 2 frequencies, faster (20 Hz) or slower (5 Hz) at 100% motor threshold, and 10 patients at sham stimulation. RESULTS: Patients at both stimulation frequencies demonstrated a superior reduction of depression severity compared to sham stimulation (active = 55.7% vs. sham = 16.3%). The response rate for active rTMS was 60%, in contrast to 10% for the sham treatment. No difference in clinical response was observed between 5 Hz and 20 Hz active rTMS. Clinical variables showed that younger age and less severe depression at entry may predict the clinical response to rTMS. Except for 1 patient in which rTMS appeared to induce mania, this procedure posed no safety problem. CONCLUSIONS: To our knowledge, this is the first study to demonstrate the clinical efficacy and safety of rTMS in Chinese patients. Since not all the rTMS trials in previous reports had positive results, further larger trials are still warranted.     

Treatment of negative symptoms of schizophrenia using repetitive transcranial magnetic stimulation in a double-blind, randomized controlled study

OBJECTIVE: To verify whether high-frequency rTMS applied above the area of the left prefrontal cortex in 15 stimulation sessions with maximum stimulation intensity is able to modify negative symptoms of schizophrenia in a double-blind, randomized controlled study. METHODS: Twenty-two patients with schizophrenia stabilized on antipsychotic medication with prominent negative symptoms were included in the trial. They were divided into two groups: eleven were treated with effective rTMS and eleven with ineffective "sham" rTMS. The ineffectiveness of the sham rTMS was achieved through the stimulation coil position. Stimulation was applied to the left dorsolateral prefrontal cortex. The stimulation frequency was 10 Hz. Stimulation intensity was 110% of the motor threshold intensity. Each patient received 15 rTMS sessions on 15 consecutive working days. Each daily session consisted of 15 applications of 10-second duration and 30-second intervals between sequences. There were 1500 stimuli per session. RESULTS: During real rTMS treatment a statistically significant decrease of negative symptoms was found (approximately 29% reduction in the PANSS negative symptom subscale and 50% reduction in the SANS). No adverse events occurred during therapy except for a mild headaches. In sham rTMS treatment a decrease of negative symptoms was also identified, but to a lesser extent than in real rTMS (about 7% in negative subscale PANSS and 13% in SANS). The change in SANS achieved statistical significance. Mutual comparison revealed a greater decrease of negative symptoms in favor of real rTMS in contrast to sham rTMS. CONCLUSION: The augmentation of rTMS enabled patients to experience a significant decrease in the severity of the negative symptoms. Our results support the therapeutic potential of rTMS at higher frequency for negative symptoms of schizophrenia.     

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.     

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 of adjuvant high frequency repetitive transcranial magnetic stimulation on negative and positive symptoms of schizophrenia: preliminary results of a double-blind sham-controlled study

The potential effect of repetitive transcranial magnetic stimulation (rTMS) on core positive and negative symptoms in schizophrenia has not yet been clearly established. The aim of this study was to examine the efficacy of adjuvant 10 Hz, suprathreshold left prefrontal rTMS in negative symptoms of schizophrenia in a double-blind sham-controlled design. Additionally, our study also investigated the suitability of applying the same stimulus condition on positive symptoms. Ten right-handed schizophrenia patients received sham or active 10 Hz suprathreshold rTMS to the left dorsolateral prefrontal cortex with psychopathology, depression and global improvement ratings before and after rTMS sessions. Compared to sham, active rTMS significantly improved negative symptoms, irrespective of change in depressive symptoms.     

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.