Naturalistic study of the use of transcranial magnetic stimulation in the treatment of depressive relapse

BACKGROUND: The efficacy of repetitive transcranial magnetic stimulation (rTMS) in the treatment of depression has been assessed in a number of acute treatment trials during the last 10 years. Little is known about the long-term impact of the treatment on the disorder and its effectiveness when applied for repeated relapses of depression over time. METHOD: Nineteen patients who had previously responded to rTMS in clinical trials received treatment with rTMS for a total of 30 episodes of depressive relapse. RESULTS: Approximately 10 months elapsed between treatment episodes. The majority of patients achieved a significant improvement in each treatment course with significant improvements achieved in patients treated with both low-frequency right-sided rTMS and high-frequency left-sided rTMS. CONCLUSIONS: The study suggests that rTMS may have value in the treatment of episodes of depressive relapse with little reduction in efficacy over time.     

A randomized double-blind sham-controlled comparison of unilateral and bilateral repetitive transcranial magnetic stimulation for treatment-resistant major depression

Abstract

Objectives. High frequency left-sided (HFL) and low frequency right-sided (LFR) unilateral repetitive transcranial magnetic stimulation (rTMS) are efficacious in treatment-resistant major depression (TRD). Similar benefit has been suggested for sequential bilateral rTMS (LFR then HFL). There are few published reports on the efficacy of sequential bilateral rTMS compared to HFL and sham rTMS. Therefore, this study evaluated the efficacy of HFL and sequential bilateral rTMS compared to sham in TRD. Methods. Subjects between the ages of 18 and 85 were recruited from a tertiary care university hospital. Seventy-four subjects with TRD and a 17-item Hamilton Depression Rating Scale (HDRS) greater than 21 were randomized to receive unilateral, bilateral, or sham rTMS. The rates of remission were compared among the three treatment groups. Results. The remission rates differed significantly among the three treatment groups using a modified intention to treat analysis that excluded subjects who did not respond to electroconvulsive therapy (ECT) during the current episode. The remission rate was significantly higher in the bilateral group than the sham group. The remission rate in the unilateral group did not differ from either group. Conclusion. These findings warrant larger controlled studies that compare the efficacy of sequential bilateral rTMS and HFL rTMS in TRD.     

Clinical effects of repetitive transcranial magnetic stimulation versus acute levodopa challenge in Parkinson's disease

We studied the short-term clinical effects of 10-Hz repetitive transcranial magnetic stimulation (rTMS) of the motor hand area contralateral to the more affected limb in 12 non-fluctuating, for at least 12 hours drug free patients with Parkinson's disease (PD). We investigated the efficacy of rTMS in combination with a levodopa challenge test design under double-blind, placebo controlled conditions. Significant reductions of UPDRS III motor scores showed the treatment conditions: placebo/rTMS, levodopa/sham stimulation and levodopa/rTMS. A more detailed evaluation of arm symptoms contralateral to the stimulated brain region showed even more pronounced effects for the three conditions. There were significant differences between the mean response of the UPDRS III arm scores to the four test conditions. In conclusion our study demonstrates short-term beneficial effects of 10-Hz rTMS on motor symptoms in PD patients. A release of endogenous dopamine in subcortical structures, i.e. putamen, in response to rTMS is the most likely mechanism of action.     

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

BACKGROUND: Multiple groups have reported on the use of repetitive transcranial magnetic stimulation (rTMS) in treatment-resistant major depression. The purpose of this study is to assess the efficacy of rTMS in unmedicated, treatment-resistant patients who meet criteria for major depression. METHODS: Depressed subjects, who had failed to respond to a median of four treatment trials, were assigned in a randomized double-blind manner to receive either active (n = 10; 20 2-sec trains of 20 Hz stimulation with 58-sec intervals; delivered at 80% motor threshold with the figure-of-eight coil positioned over the left dorsolateral prefrontal cortex) or sham (n = 10; similar conditions with the coil elevated and angled 45 degrees tangentially to the scalp) rTMS. These sequences were applied during 10 consecutive weekdays. Continuous electroencephalogram sampling and daily motor threshold determinations were also obtained. RESULTS: The group mean 25-item Hamilton Depression Rating Scale (HDRS) score was 37.2 (+/- 2.0 SEM) points. Adjusted mean decreases in HDRS scores were 14.0 (+/- 3.7) and 0.2 (+/- 4.1) points for the active and control groups, respectively (p <.05). One of 10 subjects receiving active treatment demonstrated a robust response (i.e., HDRS decreased from 47 to 7 points); three other patients demonstrated 40-45% decreases in HDRS scores. No patients receiving sham treatment demonstrated partial or full responses. CONCLUSIONS: A 2-week course of active rTMS resulted in statistically significant but clinically modest reductions of depressive symptoms, as compared to sham rTMS in a population characterized by treatment resistance.     

Theta-patterned, frequency-modulated priming stimulation enhances low-frequency, right prefrontal cortex repetitive transcranial magnetic stimulation (rTMS) in depression: a randomized, sham-controlled study

Efficacy of repetitive, transcranial magnetic stimulation (rTMS) has been found in depression; however, doubt still remains about its effectiveness in clinical practice. In this context, results are being explored. The authors, describing new techniques to improve response rates to rTMS treatment, compared the efficacy of adjuvant, frequency-modulated, active-priming rTMS with sham-priming stimulation in the theta range in patients with moderate-to-severe depression receiving low-frequency rTMS. Forty patients with moderate-to-severe depression (ICD-10 DCR) were alternately assigned to receive add-on, active-priming rTMS (4-8 Hz; 400 pulses, at 90% of motor threshold [MT]) or sham-priming stimulation followed by low-frequency rTMS (1-Hz; 900 pulses at 110% of MT) over the right dorsolateral prefrontal cortex. They were rated with the Structured Interview Guide for the Hamilton Depression Rating Scale (SIGH-D), the Brief Psychiatric Rating Scale (BPRS), and the Clinical Global Impression-Severity of Illness (CGI-S) scale at baseline, after the 5th and 10th rTMS, and 2 weeks post-rTMS. For SIGH-D scores, there was significant improvement in the active group over time. Stepwise linear-regression analysis showed that age at onset significantly predicted SIGH-D scores after the 5th rTMS session in the active-priming group. Pre-stimulation with frequency-modulated priming stimulation in the theta range has greater antidepressant effect than low-frequency stimulation alone.     

Transcranial magnetic stimulation in the treatment of depression: a double-blind, placebo-controlled trial

BACKGROUND: High-frequency left-sided repetitive transcranial magnetic stimulation (HFL-TMS) has been shown to have antidepressant effects in double-blind trials. Low-frequency stimulation to the right prefrontal cortex (LFR-TMS) has also shown promise, although it has not been assessed in treatment-resistant depression and its effects have not been compared with those of HFL-TMS. OBJECTIVE: To prospectively evaluate the efficacy of HFL-TMS and LFR-TMS in treatment-resistant depression and compared with a sham-treated control group. DESIGN: A double-blind, randomized, sham-controlled trial. SETTING: Two general psychiatric services. PARTICIPANTS: Sixty patients with treatment-resistant depression who had failed to respond to therapy with multiple antidepressant medications were divided into 3 groups of 20 that did not differ in age, sex, or any clinical variables. All patients completed the double-blind phase of the study. INTERVENTIONS: Twenty 5-second HFL-TMS trains at 10 Hz and five 60-second LFR-TMS trains at 1 Hz were applied daily. Sham stimulation was applied with the coil angled at 45 degrees from the scalp, resting on the side of one wing of the coil.Main Outcome Measure Score on the Montgomery-Asberg Depression Rating Scale. RESULTS: There was a significant difference in response among the 3 groups (F56,2 = 6.2), with a significant difference between the HFL-TMS and sham groups and between the LFR-TMS and sham groups (P<.005 for all) but not between the 2 treatment groups. Baseline psychomotor agitation predicted successful response to treatment. CONCLUSIONS: Both HFL-TMS and LFR-TMS have treatment efficacy in patients with medication-resistant major depression. Treatment for at least 4 weeks is necessary for clinically meaningful benefits to be achieved. Treatment with LFR-TMS may prove to be an appropriate initial repetitive TMS strategy in depression taking into account safety, tolerability, and efficacy considerations.     

Right versus left prefrontal transcranial magnetic stimulation for obsessive-compulsive disorder: a preliminary investigation.

BACKGROUND: There is preliminary evidence that repetitive transcranial magnetic stimulation (rTMS) may be useful for the treatment of obsessive-compulsive disorder (OCD), but no definitive study has been published, and the effect of laterality of stimulation is uncertain. METHOD: Subjects (N = 12) with resistant OCD were allocated randomly to either right or left prefrontal rTMS daily for 2 weeks and were assessed by an independent rater at 1 and 2 weeks and 1 month later. RESULTS: Subjects had an overall significant improvement in the obsessions (p < .01), compulsions (p < .01), and total (p < .01) scores on the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) after 2 weeks and at 1-month follow-up. This improvement was significant for obsessions (p < .05) and tended to significance for total Y-BOCS scores (p = .06) after correction for changes in depression scores on the Montgomery-Asberg Depression Rating Scale. There was no significant difference between right- and left-sided rTMS on any of the parameters examined. Two subjects (33%) in each group showed a clinically significant improvement that persisted at I month but with relapse later in I subject. CONCLUSION: A proportion (about one quarter) of patients with resistant OCD appear to respond to rTMS to either prefrontal lobe, although in the absence of a sham treatment group in this study, we cannot rule out the possibility of this being a placebo response. This treatment warrants further investigation to better establish its efficacy and examine the best parameters for response.     

Repetitive transcranial magnetic stimulation as treatment of poststroke depression: a preliminary study.

BACKGROUND: Depression has a significant impact on poststroke recovery and mortality. There are a proportion of patients with poststroke depression (PSD) who do not respond to antidepressants. Repetitive Transcranial Magnetic Stimulation (rTMS) might be a safe and effective alternative in these refractory cases. METHODS: We conducted a randomized, parallel, double-blind study of active versus sham left prefrontal rTMS in patients with refractory PSD. After discontinuing antidepressants, patients were randomly assigned to receive 10 sessions of active (10 Hz, 110% of the motor threshold, 20 trains of 5 seconds duration) or sham left prefrontal rTMS. Efficacy measures included HAM-D scores, response and remission rates. Patients completed a neuropsychological battery at baseline and after completing the protocol. RESULTS: When compared with sham stimulation, 10 sessions of active rTMS of the left dorsolateral prefrontal cortex were associated with a significant reduction of depressive symptoms. This reduction was not influenced by patient's age, type or location of stroke, volume of left frontal leukoaraiosis or by the distance of the stimulating coil to the prefrontal cortex. However, there was a significant positive correlation between the percentage of reduction of Ham-D scores and frontal gray and white matter volumes. There were no significant changes in cognitive functioning between the active and the sham stimulation groups. In addition, there were few and mild adverse effects that were equally distributed among groups. CONCLUSIONS: Taken together, these preliminary findings suggest that rTMS may be an effective and safe treatment alternative for patients with refractory depression and stroke.     

重复经颅磁刺激对首发精神分裂症患者血清脑源性神经营养因子的影响

目的：初步探讨高频重复经颅磁刺激（rTMS）对以阴性症状为主的首发精神分裂症患者血清脑源性神经营养因子（BDN F ）水平的影响。方法采用随机、双盲、对照研究,选取符合国际疾病分类第十版（ICD－10）中精神分裂症诊断标准的门诊患者70例。在常规抗精神病药物治疗的基础上,按照随机数字表法分为真刺激组（n ＝35）和伪刺激组（n ＝35）,并在基线时和治疗4周末时进行BDNF浓度测定和PANSS评估。结果治疗4周后,真刺激组的PANSS总分、阴性症状分和一般精神病理分均低于伪刺激组,BDNF浓度高于伪刺激组,差异均有统计学意义（P ＜0．05）。真刺激组BDNF浓度变化值与PANSS总分及各因子分变化值均无相关性（P ＞0．05）。两组不良反应差异无统计学意义（P ＞0．05）。结论 rTMS治疗可显著增加首发精神分裂症患者的血清BDNF浓度,但其浓度变化与临床症状（尤其是阴性症状）的改善无相关性。     

High (20-Hz) and low (1-Hz) frequency transcranial magnetic stimulation as adjuvant treatment in medication-resistant depression

Studies of repetitive transcranial magnetic stimulation (rTMS) in depression have found antidepressant effects when high frequency stimulation (HF-rTMS; >1 Hz) is applied over the left prefrontal cortex (LPF). A few studies have also reported success with low frequency stimulation (LF-rTMS) to the right prefrontal cortex (RPF). Both HF-rTMS and LF-rTMS have been reported to work better in areas with cerebral hypometabolism or hypermetabolism, respectively. Thirty medication-resistant patients with major depression were randomized into three groups. The first group received sham rTMS and the second group received active rTMS (20-Hz rTMS to the LPF and 1-Hz rTMS to the RPF). The third group, however, received active rTMS that was focused on different regions of the brain after examination with single photon emission computed tomography (20-Hz rTMS to an area of relatively low activity and 1-Hz rTMS to an area showing relatively high activation). Patients and raters were blind to the treatment condition. Comparison of the sham rTMS group with the overall group that received active rTMS revealed statistically significant changes on the Hamilton Rating Scale for Depression after 10 sessions. This study demonstrated that combined 20+1-Hz rTMS was effective, but no additional advantages were obtained by focusing rTMS on areas identified by single photon emission tomography as showing high versus low levels of functional activity.     

Preconditioning with transcranial direct current stimulation sensitizes the motor cortex to rapid-rate transcranial magnetic stimulation and controls the direction of after-effects.

BACKGROUND: Rapid-rate repetitive transcranial magnetic stimulation (rTMS) can produce a lasting increase in cortical excitability in healthy subjects or induce beneficial effects in patients with neuropsychiatric disorders; however, the conditioning effects of rTMS are often subtle and variable, limiting therapeutic applications. Here we show that magnitude and direction of after-effects induced by rapid-rate rTMS depend on the state of cortical excitability before stimulation and can be tuned by preconditioning with transcranial direct current stimulation (tDCS). METHODS: Ten healthy volunteers received a 20-sec train of 5-Hz rTMS given at an intensity of individual active motor threshold to the left primary motor hand area. This interventional protocol was preconditioned by 10 min of anodal, cathodal, or sham tDCS. We used single-pulse TMS to assess corticospinal excitability at rest before, between, and after the two interventions. RESULTS: The 5-Hz rTMS given after sham tDCS failed to produce any after-effect, whereas 5-Hz rTMS led to a marked shift in corticospinal excitability when given after effective tDCS. The direction of rTMS-induced plasticity critically depended on the polarity of tDCS conditioning. CONCLUSIONS: Preconditioning with tDCS enhances cortical plasticity induced by rapid-rate rTMS and can shape the direction of rTMS-induced after-effects.     

Left prefrontal repetitive transcranial magnetic stimulation in schizophrenia

In a double-blind, controlled study, we examined the therapeutic effects of high-frequency left prefrontal repetitive transcranial magnetic stimulation (rTMS) on schizophrenia symptoms. A total of 22 chronic hospitalized schizophrenia patients were randomly assigned to 2 weeks (10 sessions) of real or sham rTMS. rTMS was given with the following parameters: 20 trains of 5-second 10-Hz stimulation at 100 percent motor threshold, 30 seconds apart. Effects on positive and negative symptoms, self-reported symptoms, rough neuropsychological functioning, and hormones were assessed. Although there was a significant improvement in both groups in most of the symptom measures, no real differences were found between the groups. A decrease of more than 20 percent in the total PANSS score was found in 7 control subjects but only 1 subject from the real rTMS group. There was no change in hormone levels or neuropsychological functioning, measured by the MMSE, in either group. Left prefrontal rTMS (with the used parameters) seems to produce a significant nonspecific effect of the treatment procedure but no therapeutic effect in the most chronic and severely ill schizophrenia patients.     

Changes in motor cortical excitability induced by high-frequency repetitive transcranial magnetic stimulation of different stimulation durations.

OBJECTIVE: To investigate the changes in cortical excitability of the human motor cortex induced by high-frequency repetitive transcranial magnetic stimulation (rTMS) of different stimulation durations. METHODS: Twenty healthy subjects participated in the study. Subjects received 20 trains of 10-Hz rTMS at 80% of the resting motor threshold (RMT) intensity with two different stimulation durations (5 and 1.5s) over the motor hot spot for left first dorsal interosseous (FDI) muscle. Electromyographic responses (motor-evoked potentials, MEPs) to single-pulse stimulation, and intracortical inhibition (ICI) and intracortical facilitation (ICF) by paired-pulse stimulation were measured bilaterally in the relaxed FDI muscles before, immediately after, and 30, 60, 90 and 120 min after rTMS. RESULTS: After 5s of 10-Hz rTMS, the mean amplitude of MEP for the stimulated M1 cortex decreased for up to 90min (P=0.002) and that of the unstimulated M1 cortex decreased for up to 60 min (P=0.008). Enhancement of ICI and suppression of ICF were observed and sustained for more than 90 min in both stimulated (P=0.001) and unstimulated (P=0.003) M1 cortex after 5s of 10-Hz rTMS. After 1.5s of 10-Hz rTMS, the mean amplitude of MEP increased in stimulated cortex for up to 120 min (P=0.005). CONCLUSIONS: With different stimulation durations, high-frequency subthreshold rTMS can produce different patterns of long-lasting changes in corticospinal and intracortical excitability in stimulated and unstimulated motor cortex in healthy subjects. SIGNIFICANCE: The results have important implications for the selection of stimulation parameters other than the frequency of rTMS. The clinical application of rTMS for the purpose of motor enhancement should be considered along with the mechanism of different stimulation parameters.     

低频重复经颅磁刺激对难治性精神分裂症的增效作用

目的评价低频重复经颅磁刺激(r TMS)对难治性精神分裂症的疗效和认知功能的影响及其安全性。方法将52例幻听症状突出的难治性精神分裂症患者随机分为真刺激组和伪刺激组,刺激频率为1Hz,部位为背外侧前额叶皮质。在基线期、2周(治疗10次)、6周(治疗20次)和治疗结束后1个月采用阳性和阴性症状量表(PANSS)、幻听量表(AHRS)、临床总体印象量表(CGIS)评价精神症状,采用可反复测查的成套神经心理状态评估工具(RBANS)评价认知功能,采用副反应量表(TESS)评定不良反应。结果 r TMS治疗10次、20次及随访1个月时,真刺激组和伪刺激组相比,PANSS幻觉、CGI评分、AHRS频率及RBANS总评分比较差异均有统计学意义(P0.05或0.01);r TMS治疗20次及随访1个月时,AHRS总评分、影响、痛苦、RBANS视觉广度、言语功能及注意力评分差异有统计学意义(P0.05或0.01);随访1个月时,PANSS阳性症状、一般病理症状评分、RBANS即刻记忆评分差异有统计学意义(P0.05或0.01)。r TMS治疗后未发现明显不良反应。结论低频r TMS可改善精神分裂症的幻听、阳性症状和认知功能且安全性好。     

Repetitive transcranial magnetic stimulation for the treatment of negative symptoms in residual schizophrenia: rationale and design of a sham-controlled,randomized multicenter study

Current meta-analysis revealed small, but significant effects of repetitive transcranial magnetic stimulation (rTMS) on negative symptoms in patients with schizophrenia. There is a need for further controlled, multicenter trials to assess the clinical efficacy of rTMS on negative symptoms in schizophrenia in a larger sample of patients. The objective of this multicenter, randomized, sham-controlled, rater- and patient-blind clinical trial is to investigate the efficacy of 3-week 10-Hz high frequency rTMS add on to antipsychotic therapy, 15 sessions per 3 weeks, 1,000 stimuli per session, stimulation intensity 110% of the individual motor threshold) of the left dorsolateral prefrontal cortex for treating negative symptoms in schizophrenia, and to evaluate the effect during a 12 weeks of follow-up. The primary efficacy endpoint is a reduction of negative symptoms as assessed by the negative sum score of the positive and negative symptom score (PANSS). A sample size of 63 in each group will have 80% power to detect an effect size of 0.50. Data analysis will be based on the intention to treat population. The study will be conducted at three university hospitals in Germany. This study will provide information about the efficacy of rTMS in the treatment of negative symptoms. In addition to psychopathology, other outcome measures such as neurocognition, social functioning, quality of life and neurobiological parameters will be assessed to investigate basic mechanisms of rTMS in schizophrenia. Main limitations of the trial are the potential influence of antipsychotic dosage changes and the difficulty to ensure adequate blinding.

     

Left prefrontal activation predicts therapeutic effects of repetitive transcranial magnetic stimulation (rTMS) in major depression

There is evidence that repetitive transcranial magnetic stimulation (rTMS) applied to the prefrontal cortex has antidepressive properties. In the present study we evaluated the clinical status and the hemodynamic responses during mental work in the prefrontal cortex before therapeutic rTMS. Twelve patients diagnosed with major depression (DSM-IV) were randomized in a sham-controlled cross-over treatment protocol of 4 weeks' duration consisting of two periods of 5 days with rTMS separated by 9 days of no stimulation. rTMS (10 Hz) was applied to the left dorsolateral prefrontal cortex. Hemodynamic changes in the prefrontal cortex during mental work were evaluated by multi-site near-infrared spectroscopy (NIRS). Scores on the Hamilton Depression Rating Scale (HAMD) decreased significantly by -5.4 points after 5 days of active stimulation, whereas it did not change (+1.6 points) after sham stimulation. Absence of a task-related increase of total hemoglobin concentrations at the stimulation site (P<0.005), but not at other locations, before the first active rTMS significantly predicted the clinical response to active rTMS. Clinical benefits of rTMS are predicted by low local hemodynamic responses and support the idea of activation-dependent targeting of rTMS location.     

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.     

Transcranial magnetic stimulation in treatment-resistant depressed patients: a double-blind, placebo-controlled trial

This 5-week, randomized, double-blind, placebo-controlled trial investigated the efficacy and tolerability of high frequency repetitive transcranial magnetic stimulation (rTMS) directed to the left prefrontal cortex in drug-resistant depressed patients. Fifty-four patients were randomly assigned to receive 10 daily applications of either real or sham rTMS. Subjects assigned to receive active stimulation were divided into two further subgroups according to the intensity of stimulation: 80% vs. 100% of motor threshold (MT). At study completion, the response rates were 61.1% (n=11), 27.8% (n=5) and 6.2% (n=1) for the 100% MT group, 80% MT group and sham group, respectively. A significant difference (Pearson chi(2) test) was found between the 100% MT and sham groups, while the 80% MT group did not differ significantly from the sham group. Between the two active groups, a marginally significant difference was observed. Analysis of variance with repeated measures on Hamilton Depression Rating Scale scores revealed a significantly different decrease over time of depressive symptomatology among the three treatment groups. Treatment response appeared to be unrelated to the demographic and clinical characteristics recorded, and on the whole the technique was well tolerated. The results of this double-blind trial showed that rTMS may be a useful and safe adjunctive treatment for drug-resistant depressed patients.     

Treating auditory hallucinations by transcranial magnetic stimulation: a randomized controlled cross-over trial

BACKGROUND: In a previous functional magnetic resonance imaging study, the authors succeeded in demonstrating the activation of Heschl's gyrus during auditory hallucinations (AH). OBJECTIVES: This study aims to treat AH specifically by repetitive transcranial magnetic stimulation (rTMS). METHODS: 16 patients with AH were included in a randomized, cross-over, sham-controlled trial. 1 Hz rTMS was administered over the left and right temporo-parietal cortex and sham position, respectively, on 5 consecutive days; 900 stimuli each, strength 100% of motor threshold. Using the Psychotic Symptom Rating Scales (PSYRATS), the hallucinations during the stimulation periods and 4-week follow-ups were quantified. Electroencephalograms (EEG) were acquired before and after each period. RESULTS: Treatment responses were observed after left hemisphere rTMS only. The 5 patients who showed a response did so already after 2 days. However, group mean hallucination scores did not differ across treatment conditions. No significant changes were found in EEG after rTMS. CONCLUSIONS: A subgroup of patients suffering from AH benefits soon after treatment start from rTMS over the left superior temporal gyrus as revealed by the decrease of AH scores compared to right-sided and sham procedures.     

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.