Right prefrontal slow repetitive transcranial magnetic stimulation in schizophrenia: a double-blind sham-controlled pilot study.

BACKGROUND: The aim of this study was to extend our previous work on the therapeutic efficacy of repetitive transcranial magnetic stimulation (rTMS) in major depression to patients with schizophrenia. METHODS: Thirty-five inpatients with schizophrenia were randomly assigned to either right prefrontal rTMS or sham treatment and were rated before and after treatment for positive, negative, and depressive symptoms. RESULTS: Thirty-one subjects (rTMS = 16, sham = 15) completed a 2-week treatment protocol. No serious adverse effects were reported; however, rTMS was not superior to sham treatment on any of the clinical ratings. CONCLUSIONS: In contrast to our previous positive findings in major depression, right prefrontal slow rTMS does not appear to have a beneficial effect for actively psychotic patients with schizophrenia.     

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 of the right dorsolateral prefrontal cortex in posttraumatic stress disorder: a double-blind, placebo-controlled study

OBJECTIVE: The efficacy of repetitive transcranial magnetic stimulation (rTMS) of the right prefrontal cortex was studied in patients with posttraumatic stress disorder (PTSD) under double-blind, placebo-controlled conditions. METHOD: Twenty-four patients with PTSD were randomly assigned to receive rTMS at low frequency (1 Hz) or high frequency (10 Hz) or sham rTMS in a double-blind design. Treatment was administered in 10 daily sessions over 2 weeks. Severity of PTSD, depression, and anxiety were blindly assessed before, during, and after completion of the treatment protocol. RESULTS: The 10 daily treatments of 10-Hz rTMS at 80% motor threshold over the right dorsolateral prefrontal cortex had therapeutic effects on PTSD patients. PTSD core symptoms (reexperiencing, avoidance) markedly improved with this treatment. Moreover, high-frequency rTMS over the right dorsolateral prefrontal cortex alleviated anxiety symptoms in PTSD patients. CONCLUSIONS: This double-blind, controlled trial suggests that in PTSD patients, 10 daily sessions of right dorsolateral prefrontal rTMS at a frequency of 10 Hz have greater therapeutic effects than slow-frequency or sham stimulation.     

Slow right prefrontal transcranial magnetic stimulation as a treatment for medication-resistant depression: a double-blind, placebo-controlled study

Over the past decade, efforts have been made to assess the positive therapeutic effects of transcranial magnetic stimulation (TMS) by altering the excitability of the brain. We conducted a double-blind, placebo-controlled study to assess the efficacy of right prefrontal slow repetitive TMS in patients with treatment refractory major depression. This pilot study supports the therapeutic potential of rTMS in the low-frequency range of 1 Hz on right prefrontal cortex for the treatment of refractory major depression. Additional studies will be necessary to assess the efficacy of rTMS with different indices (frequency, intensity, and stimulation site) for major depression and other psychiatric diseases.     

Repetitive transcranial magnetic stimulation over the orbitofrontal cortex for obsessive-compulsive disorder: a double-blind,crossover study

This pilot study was designed to assess the efficacy of low-frequency repetitive transcranial magnetic stimulation (rTMS) over the right orbitofrontal cortex (OFC) by means of a double-cone coil in patients suffering from obsessive-compulsive disorder. We hypothesized that low-frequency stimulation of the OFC would lead to a reduction in clinical symptoms, as measured on the Yale-Brown Obsessive Compulsive Scale (Y-BOCS). A randomized, double-blind, crossover design was implemented with two 1-week treatment periods (active stimulation versus sham stimulation) separated by a 1-month washout period. Concomitantly, a subgroup of patients underwent a positron emission tomography (PET) scan after each stimulation sequence. Statistical analyses compared the Y-BOCS scores at the end of each period. At day 7, we observed a significant decrease from baseline in the Y-BOCS scores, after both active (P<0.01) and sham stimulation (P=0.02). This decrease tended to be larger after active stimulation than after sham stimulation: −6 (−29, 0) points versus −2 (−20, 4) points (P=0.07). Active versus sham PET scan contrasts showed that stimulation was related to a bilateral decrease in the metabolism of the OFC. The OFC should definitely be regarded as a key neuroanatomical target for rTMS, as it is easier to reach than either the striatum or the subthalamic nucleus, structures favored in neurosurgical approaches.     

High-rate repetitive transcranial magnetic stimulation in migraine prophylaxis: a randomized, placebo-controlled study

Repetitive transcranial magnetic stimulation (rTMS) is an emerging treatment for pain but there is no class 1 study on its role in migraine prophylaxis. In this study we report the efficacy and safety of high-rate rTMS in migraine prophylaxis. Adult migraine patients having >4 attacks/month were randomized to high-rate rTMS or sham stimulation. Stimulation in the form of 10 Hz rTMS, 600 pulses in 10 trains were delivered to the hot spot of the right abductor digiti minimi in 412 s. Three sessions were delivered on alternate days. The outcome was defined at 1 month. The primary outcome measures were reduction in headache frequency and severity >50 % as assessed by the Visual Analogue Scale (VAS). The secondary outcome measures were functional disability, rescue medication and adverse events. Fifty patients each were randomized to rTMS or sham stimulation. The baseline characteristics of rTMS and sham stimulation groups were similar. At 1 month, headache frequency (78.7 vs. 33.3 %; P = 0.0001) and VAS score (76.6 vs. 27.1 %; P = 0.0001) improved significantly in the patients receiving rTMS compared to those in the sham stimulation group. Functional disability also improved significantly in rTMS group (P = 0.0001). Only one patient following rTMS developed transient drowsiness and was withdrawn from the study. This study provides evidence of the efficacy and safety of 10 Hz rTMS in migraine prophylaxis.     

Therapeutic efficacy of right prefrontal slow repetitive transcranial magnetic stimulation in major depression: a double-blind controlled study

BACKGROUND: Transcranial magnetic stimulation (TMS), a noninvasive technique for stimulation of the brain, has recently been suggested to be effective for the treatment of major depression. We conducted a double-blind, placebo-controlled study to assess the efficacy of slow repetitive TMS (rTMS) in patients with major depression. METHODS: Seventy patients with major depression (53 women, 17 men; mean age, 58.7 years; SD, 17.2 years) were randomly assigned to receive rTMS or sham rTMS in a double-blind design. Treatment was administered in 10 daily sessions during a 2-week period. Severity of depression was blindly assessed before, during, and after completion of the treatment protocol. RESULTS: All patients completed the first week of treatment and 67 completed the entire protocol. Patients who received rTMS had a significantly greater improvement in depression scores compared with those who received sham treatment. At the end of 2 weeks, 17 of 35 patients in the rTMS group, but only 8 of 32 in the sham-treated group, had an improvement of greater than 50% in their depression ratings. CONCLUSIONS: This controlled study provides evidence for the short-term efficacy of slow rTMS in patients with recurrent major depression. Additional studies will be necessary to assess the efficacy of rTMS as compared with electroconvulsive therapy as well as the long-term outcome of this treatment in major depression and possibly other psychiatric disorders.     

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.     

Antidepressant effects of high and low frequency repetitive transcranial magnetic stimulation to the dorsolateral prefrontal cortex: a double-blind, randomized, placebo-controlled trial

Repetitive transcranial magnetic stimulation (rTMS) has antidepressant effects in patients with major depressive disorder. The mechanisms of action and optimal stimulation parameters remain unclear. To test the hypothesis that rTMS exerts antidepressant effects either by enhancing left dorsolateral prefrontal cortex (DLPFC) excitability or by decreasing right DLPFC excitability, the authors studied 45 patients with unipolar recurrent major depressive disorder in a double-blind, randomized, parallel group, sham-controlled trial. Patients were randomized to receive 1 Hz or 10 Hz rTMS to the left DLPFC, 1 Hz to the right DLPFC or sham TMS. Left 10 Hz and right 1 Hz rTMS showed similar significant antidepressant effects. Other parameters led to no significant antidepressant effects.     

Muscle vibration and prefrontal repetitive transcranial magnetic stimulation

We previously demonstrated that prefrontal subthreshold repetitive transcranial magnetic stimulation (rTMS) may reduce motor cortex excitability. We have now examined whether muscle vibration (MV) can compensate for this depression. We enrolled 25 healthy volunteers (aged 22 to 37 years) who received 5 HZ, 10% subthreshold prefrontal rTMS for 12 s. The extensor carpi radialis muscle was vibrated with an electromagnetic mechanical stimulator with a stimulation frequency of 120 HZ and 0.5 mm amplitude. Motor evoked potentials (MEPs) from the flexor carpi radialis muscle (FCR) following single-pulse transcranial magnetic stimulation (TMS) were recorded at baseline, and after 4, 8, and 12 s. During prefrontal rTMS, MEPs of the FCR exhibited a serial depression (P = 0.001). This effect did not occur during MV. We conclude that rTMS of the prefrontal cortex may inhibit the corticospinal system. This depression may be compensated by MV, suggesting that vibration changes motor cortex excitability. The underlying mechanism might be an input from Ia sensory afferents to the motor and prefrontal cortex.     

舍曲林单用与合并重复经颅磁刺激治疗难治性强迫症患者临床对照研究

目的:比较舍曲林单用或合并重复经颅磁刺激(r TMS)治疗难治性强迫症患者的临床疗效。方法:将60例强迫症患者随机分成研究组(舍曲林+r TMS)和对照组(舍曲林+r TMS伪刺激),疗程8周。治疗前及治疗2、4、6、8周后进行耶鲁布朗强迫症状量表(Y-BOCS)评定,治疗2、4、6、8周后进行治疗中出现的症状量表(TESS)评定,治疗前后进行世界卫生组织生活质量测定量表(WHOQOL-100)评定。结果:治疗4周末起两组Y-BOCS评分较治疗前显著降低(P均0.01);且研究组评分较对照组下降更显著(t=3.536、2.367、2.519;P0.05或P0.01)。治疗8周末研究组总有效率(92.9%)显著高于对照组(67.8%)(P0.05)。在治疗第8周末,研究组WHOQOL-100中社会关系、独立性、心理及生理评分显著高于对照组(P0.05或P0.01);治疗第4周末研究组TESS评分显著高于对照组(P0.01)。结论:舍曲林联合r TMS对难治性强迫症患者的疗效及生活质量影响均优于单用舍曲林。     

Subthreshold prefrontal repetitive transcranial magnetic stimulation reduces motor cortex excitability

The prefrontal cortex plays an important role in central motor control. We have examined whether prefrontal repetitive transcranial magnetic stimulation (rTMS) induces changes of motor cortex excitability determined by motor evoked potentials (MEPs) following single-pulse TMS. We studied 18 healthy volunteers stimulated at 5 Hz with 10% subthreshold prefrontal vs. occipital rTMS for 12 s. MEPs from the flexor carpi radialis muscle after single-pulse vertex stimulation were recorded during rTMS at 0, 4, 8, and 12 s. MEP areas decreased significantly after 8 s of prefrontal rTMS (P < 0. 05) but not after occipital rTMS. We conclude that rTMS of the prefrontal cortex may inhibit the primary motor areas.     

Effect of left prefrontal repetitive transcranial magnetic stimulation on food craving.

BACKGROUND: Dysfunction of the prefrontal cortex is implicated in craving for drugs and food. This study explores the effect of prefrontal cortex stimulation on food craving. METHODS: In a randomized double-blind parallel group study, 28 women, who reported frequent cravings for food were exposed to foods that typically elicit strong cravings before and after a single session of real or sham 10-Hz repetitive transcranial magnetic stimulation to the left dorsolateral prefrontal cortex at an intensity of 110% individual motor threshold. RESULTS: Self-reported food craving during exposure to the experimental foods remained stable before and after real stimulation compared with sham stimulation in which cravings increased over the experimental session. Consumption of snack foods within a 5-min period after stimulation did not differ between groups. CONCLUSIONS: Prefrontal stimulation inhibits the development of craving. A longer period of observation is necessary to establish whether there is an effect on food consumption.     

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.     

低频重复经颅磁刺激对强迫症患者执行功能的影响

目的：探讨低频重复经颅磁刺激(rTMS)对强迫症患者执行功能的影响.方法30例强迫症(OCD)患者随机分为研究组和对照组,研究组给予舍曲林联合6周 rTMS 治疗;对照组给予舍曲林联合6周的 rTMS 伪刺激治疗.采用耶鲁－布朗量表(Y－BOCS)对两组患者于治疗前及治疗6周末进行疗效评定,并采用威斯康星卡片分类测验(WCST)及 Stroop 色词测验评估执行功能.结果 Y－BOCS 评分显示,研究组疗效较对照组好,差异有统计学意义(P ＜0．05). WSCT 评分结果显示,研究组治疗前后总操作时间、完成归类数和持续性错误改变量明显高于对照组,差异有统计学意义(P ＜0.05). Stroop 色词测验结果显示,研究组治疗前后的所有测验的测试时间改变量明显高于对照组,差异有统计学意义(P ＜0．05).结论两组 OCD 患者的临床症状及执行功能在治疗后均有改善,而且联合 rTMS 治疗效果更好.     

低频重复经颅磁刺激联合氟伏沙明治疗儿童青少年首发强迫障碍的临床双盲随机对照研究

目的 探讨低频重复经颅磁刺激（rTMS）联合氟伏沙明治疗儿童青少年首发强迫障碍的临 床疗效。方法 选取2021年6月至2022年3月在青岛市精神卫生中心门诊和住院的58例首发强迫障碍 患儿为研究对象,采用随机数字表法分为试验组和对照组,每组 29 例。试验组采用低频 rTMS 联合氟伏 沙明治疗,对照组采取伪刺激联合氟伏沙明治疗,两组均观察治疗 8 周。采用耶鲁 - 布朗强迫障碍量表 （Y-BOCS）、汉密尔顿焦虑量表（HAMA）、不良反应症状量表（TESS）对两组患儿进行评估。采用重复测量 方差分析比较治疗前及治疗第 2、4、6、8 周末两组患儿的强迫症状严重程度、焦虑情况,并比较两组患 儿的治疗总有效率和不良反应发生率。结果 两组患儿治疗前的Y-BOCS、HAMA 评分比较,差异无统 计学意义（P＞ 0.05）。试验组患儿治疗第 2、4、6、8 周末的 Y-BOCS 评分与对照组比较［（26.10±5.11）分 比（30.24±3.79）分、（22.48±5.09）分比（25.76±4.60）分、（17.34±5.15）分比（20.31±5.65）分、（12.59±5.82）分比 （16.31±6.71）分］,差异均有统计学意义（均P＜ 0.05）;HAMA 评分与对照组比较［分别为（19.41±4.02）分 比（22.55±3.88）分、（15.62±4.53）分比（18.90±3.39）分、（11.66±3.11）分比（15.62±3.23）分、（8.31±2.19）分 比（12.55±2.68）分］,差异均有统计学意义（均P＜ 0.01）。重复测量方差分析结果显示,两组患儿的 Y-BOCS、HAMA 评分存在组间、时间和交互效应,差异均有统计学意义（均P＜ 0.05）。进一步分析显示, 试验组在治疗第 2 周末起效,而对照组在治疗第 4 周末起效。试验组的治疗总有效率为 93.11%（27/29）, 高于对照组的 72.41%（21/29）,差异有统计学意义（Z=1.980,P＜ 0.05）。两组患儿的不良反应发生率比较 ［37.93%（11/29）比 27.59%（8/29）］,差异无统计学意义（χ2 =0.704,P＞ 0.05）。结论 低频 rTMS 联合氟伏 沙明治疗儿童青少年首发强迫障碍能够改善患儿的强迫症状和焦虑症状,治疗2周可起效,有效率较高。     

A double-blind, placebo-controlled trial of clonazepam in obsessive-compulsive disorder.

Selective serotonin reuptake inhibitors (SSRIs) are currently the first-line pharmacological agents in treating obsessive-compulsive disorder (OCD). Appropriate treatment for OCD also involves cognitive behavioural therapy (CBT), including exposure and response prevention. As there is a time delay in seeing full therapeutic response, and not all patients tolerate SSRIs, there remains an unmet need for additional treatment approaches in OCD. In addition, most responders report only a partial reduction in symptoms. Clonazepam has demonstrated effectiveness in several preliminary reports in treating OCD. Twenty-seven patients with OCD were entered into a 10 week, double-blind, parallel design trial of clonazepam vs. placebo. Overall, only 3 out of 25 patients who had >/= 1 rating on clonazepam/placebo were judged to be treatment responders, by scoring a 1 (very much improved) or 2 (much improved) on the CGI improvement scale. Responders included 2 of 9 in the placebo group and 1 of 16 in the clonazepam group. No significant difference was found between clonazepam and placebo groups on responder/non responder status (Chi(2 )=1.39, df =1,24, p=0.238), nor on change in YBOCS, Ham-A, Ham-D or NIMH scales from beginning to last evaluation carried forward. These findings suggest that clonazepam is not effective as monotherapy in treating OCD. Its effectiveness in specific subgroups of OCD patients with co-morbid anxiety disorders or as an augmentation strategy added to SSRIs remains to be determined.     

Lack of prefrontal repetitive transcranial magnetic stimulation effects in time production processing

The aim of the present study was to determine the effects of high frequency repetitive transcranial magnetic stimulation (rTMS) over different neuroanatomical areas [left and right doroslateral prefrontal cortex (DLPFC) and right cerebellar hemisphere] on time production task. The study was performed in 16 healthy right-handed men with a cross-over, within subject repeated measures design. There were four rTMS conditions: baseline without stimulation, high frequency rTMS over right, left DLPFC and over right cerebellum. The volunteers were asked to produce a 3-min interval by internal counting. The rTMS was applied during the task. No significantly differences were observed in absolute error scores in time estimation task with any rTMS condition. This preliminary study does not support the role of the prefrontal lobe in time production processes.     

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.