Therapeutic efficacy of right prefrontal slow repetitive transcranial magnetic stimulation in major depression: a double-blind controlled study. A controlled trial of daily left prefrontal cortex TMS for treating depression. Substitution of rapid transcranial magnetic stimulation treatments for electroconvulsive therapy treatments in a course of electroconvulsive therapy. Transcranial magnetic stimulation: a novel antidepressive strategy? Frequency dependence of antidepressant response to left prefrontal repetitive transcranial magnetic stimulation (rTMS) as a function of baseline cerebral glucose metabolism. Double-blind controlled investigation of transcranial magnetic stimulation for the treatment of resistant major depression. Mood improvement following daily left prefrontal repetitive transcranial magnetic stimulation in patients with depression: a placebo-controlled crossover trial. A randomized clinical trial of repetitive transcranial magnetic stimulation in the treatment of major depression. Repetitive transcranial magnetic stimulation (rTMS) in pharmacotherapy-refractory major depression: comparative study of fast, slow and sham rTMS. Three and six-month outcome following courses of either ECT or rTMS in a population of severely depressed individuals--preliminary report. Repetitive transcranial magnetic stimulation in the treatment of medication-resistant depression: preliminary data. Modest adjunctive benefit with transcranial magnetic stimulation in medication-resistant depression. Repetitive transcranial magnetic stimulation: a putative add-on treatment for major depression in elderly patients. Prefrontal repetitive transcranial magnetic stimulation as add on treatment in depression.
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.
                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.
                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.
                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. Transcranial magnetic stimulation (TMS) is a new technology for noninvasively stimulating the brain. Several studies have suggested that daily stimulation of the left prefrontal cortex with TMS for 2 weeks has probable antidepressant effects. We conducted a parallel-design, double-masked, sham-controlled study to address whether 2 weeks of daily TMS over the left prefrontal cortex has antidepressant activity greater than sham.
                Thirty medication-free adult outpatients with nonpsychotic, major depressive (n = 21) or bipolar (n = 9) (depressed phase) disorder who were in a current major depression (Hamilton Rating Scale for Depression [HRSD] 21-item score of >18) were treated each weekday for 2 weeks. Subjects were randomly assigned to receive either daily active (20 subjects) or sham (10 subjects) stimulation. Additionally, the 20 active subjects were equally divided between slower (5 Hz) and faster (20 Hz) frequency treatment. Antidepressant response was defined as greater than a 50% improvement in the baseline HRSD.
                Active TMS resulted in significantly more responders (9/20) than did sham (0/10) (chi(2) = 6.42, p <.01). The number of responders did not differ significantly between the two active cells (3/10 faster and 6/10 slower). Expressed as a percent change from baseline, active TMS subjects had significantly greater improvement on the Beck Depression Inventory as well as the Hamilton Anxiety Rating Scale than did those who received sham.
                Daily left prefrontal TMS for 2 weeks significantly reduced depression symptoms greater than did sham. The two forms of active TMS treatment did not differ significantly. Our aim was to determine whether rTMS treatments could be substituted for ECT treatments in a course of ECT, 1) without loss of antidepressant effect, and 2) without increase in subjective side-effects. We used a randomized, single-blind, controlled study. Two streams were conducted. Stream 1 received non-dominant unilateral (UL) ECT only, treatments being given 3 times per week for 2 weeks. Stream 2 received a combination of treatments: one UL ECT on Day 1 and rTMS on the following 4 days, all repeated once, after a 2-day respite. Twenty-two patients were recruited and 11 were allocated to each stream. There was no evidence that the antidepressant effect of the ECT only stream was superior to that of the ECT plus rTMS stream. There was no increase in subjective side-effects in the ECT plus rTMS stream. On the contrary, this stream was accompanied by less side effects than the ECT only stream in this study. In conclusion, we have determined that it is possible to substitute rTMS treatments for ECT treatments in a course of ECT without loss of antidepressant effect or an increase in subjective side-effects, using the described parameters. It is possible that the combination of ECT plus rTMS will provide a means of avoiding some of the subjective side-effects encountered with the conventional course of ECT. Further studies are indicated. Transcranial magnetic stimulation (TMS) is a well-established diagnostic probe in neurological practice. The increasing knowledge of biological mechanisms in electroconvulsive therapy presents a clear case for studying the applicability of TMS as a therapeutic tool in psychiatry. Based on the results of our pilot study showing a possible antidepressive effect of TMS, we conducted a controlled clinical trial on patients affected by major depression (DSM-III-R). Group 1 (n = 12) underwent TMS as add-on therapy to standard antidepressive medication, while group 2 (n = 12) was treated only with antidepressive medication. Already after the third add-on TMS session, a statistically significantly greater remission of depressive symptoms occurred in the patients of group 1 (p = 0.003). This statistically significant difference between the groups became even more marked on the last day of the study (p = 0.001, Wilcoxon). The results and further implications of TMS in psychiatric disorders are discussed. Recent studies suggest that both high frequency (10-20 Hz) and low frequency (1 Hz) repetitive transcranial magnetic stimulation (rTMS) have an antidepressant effect in some individuals. Electrophysiologic data indicate that high frequency rTMS enhances neuronal firing efficacy and that low frequency rTMS has the opposite effect.
                We investigated the antidepressant effects of 10 daily left prefrontal 1 Hz versus 20 Hz rTMS with the hypothesis that within a given subject, antidepressant response would differ by frequency and vary as a function of baseline cerebral glucose metabolism. After baseline PET scans utilizing [18F]-Fluorodeoxyglucose, thirteen subjects participated in a randomized crossover trial of 2 weeks of 20 Hz paired with 2 weeks 1 Hz or placebo rTMS.
                We found a negative correlation between degree of antidepressant response after 1 Hz compared to 20 Hz rTMS (r = -0.797, p < .004). Additionally, better response to 20 Hz was associated with the degree of baseline hypometabolism, whereas response to 1 Hz rTMS tended to be associated with baseline hypermetabolism.
                These preliminary results suggest that antidepressant response to rTMS might vary as a function of stimulation frequency and may depend on pretreatment cerebral metabolism. Further studies combining rTMS and functional neuroimaging are needed. The efficacy and safety of left prefrontal repetitive transcranial magnetic stimulation (rTMS) for treating resistant major depression were examined in a double-blind, controlled study.
                Eighteen medication-resistant depressed subjects were randomly assigned to 2 weeks of real or sham rTMS, then permitted up to 4 weeks of real rTMS. Effects on mood, neuropsychological function, EEG, and hearing were assessed.
                The groups receiving real and sham rTMS improved in mood significantly over the 2-week double-blind period, but there was no significant difference between groups.
                Repetitive transcranial magnetic stimulation did not provide significantly greater improvement than did sham treatment. A 4-week course of rTMS, as administered in this study, was safe. Preliminary studies have indicated that daily left prefrontal repetitive transcranial magnetic stimulation might have antidepressant activity. The authors sought to confirm this finding by using a double-blind crossover design.
                Twelve depressed adults received in random order 2 weeks of active treatment (repetitive transcranial magnetic stimulation, 20 Hz at 80% motor threshold) and 2 weeks of sham treatment.
                Changes from the relevant phase baseline in scores on the 21-item Hamilton depression scale showed that repetitive transcranial magnetic stimulation significantly improved mood over sham treatment. During the active-treatment phase, Hamilton depression scale scores decreased 5 points, while during sham treatment the scores increased or worsened by 3 points. No adverse effects were noted.
                These placebo-controlled results suggest that daily left prefrontal repetitive transcranial magnetic stimulation has antidepressant activity when administered at these parameters. Further controlled studies are indicated to explore optimal stimulation characteristics and location, potential clinical applications, and possible mechanisms of action. 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.
                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.
                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.
                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. 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. Recent studies have strengthened the claim that repetitive transcranial magnetic stimulation (rTMS) is an effective treatment for major depression. The longitudinal outcome of TMS-treated patients, however, has not been described. We report on the 3- and 6-month outcomes of a group of patients treated with either electroconvulsive therapy (ECT) (n = 20) or (rTMS) (n = 21).
                Patients diagnosed with major depressive disorder with or without psychotic features referred for ECT were randomly assigned to receive either ECT or rTMS. Forty-one patients who responded to either treatment constituted the sample. Patients were followed on a monthly basis and outcomes were determined with the Hamilton Rating Scale for Depression-17 items (HRSD) and the Global Assessment of Functioning (GAF) scales. Medications were routinely prescribed.
                There were no differences in the 6-month relapse rate between the groups. Overall, 20% of the patients relapsed (four from the ECT group and four from the rTMS group). Patients reported equally low and not significantly different scores in the HRSD (ECT group 8.4 +/- 5.6 and TMS group 7.9 +/- 7.1) and the GAF (ECT group 72.8 +/- 12 and TMS group 77.8 +/- 17.1) at the 6-month follow up.
                Patients treated with rTMS do as well as those treated with ECT at the 3- and 6-month follow-up points. These data suggest that the clinical gains obtained with rTMS last at least as long as those obtained with ECT. nan Controverted results have been obtained using high frequency transcranial magnetic stimulation (HF-rTMS) as an antidepressant treatment.
                Forty patients suffering from drug-resistant major depression received ten sessions of HF-rTMS at 90% of the motor threshold on the left prefrontal cortex or sham stimulation, added to their pharmacological treatment, in a randomized double-blind design. In a second open phase, patients still fulfilling criteria of inclusion received ten additional sessions of HF-rTMS at 90 or 110%.
                Real, but not sham HF-rTMS, was associated with a significant decrease in the Hamilton Depression Rating Scale, but only twelve patients decreased more than 50%. Conclusions: Left prefrontal HF-rTMS was effectively associated with antidepressant treatment, although the size effect was small.
                Shortage of the sample and control difficulties of the placebo effect.
                Questionable in more than half of the patients studied. Repetitive transcranial magnetic stimulation (rTMS) is a recent putative treatment for affective disorders. Several studies have demonstrated antidepressant effects of rTMS in younger patients; we aimed to assess its effect in older outpatients with treatment-resistant major depression. Twenty-four outpatients (mean age=62 years, S.D.=12) with major depression were randomized for sham or real stimulation and received 10 daily rTMS sessions (20 Hz, 2-s trains, 28-s intertrain intervals, 100% of motor threshold) in addition to the antidepressant medication. For sham stimulation, the coil was tilted 90 degrees. Depression severity was assessed using the Hamilton Depression Rating Scale, the Beck Depression Inventory, items from the NIMH self-rated symptom scale, and a visual analog depression scale. Mini-Mental Status Examination performance, memory, and executive and attentional functions were measured to control for cognitive side effects. Depression ratings revealed significant antidepressant effects within 2 weeks in both sham and real stimulation groups; however, there were no between-group differences. Treatment with rTMS was safe; adverse events were rare and not more prevalent in either group, and cognitive assessment did not show any deterioration. We were unable to demonstrate any additional antidepressant effects of real stimulation in elderly patients with treatment-resistant major depression. Therapeutic effects of rTMS in this clinically challenging patient group remain to be demonstrated. A growing number of studies report antidepressant effects of repetitive transcranial magnetic stimulation (rTMS) in patients with major depression. The hypothesis that high frequency (20 Hz) rTMS (HF-rTMS) may speed up and strengthen the therapeutic response to sertraline in MD was tested. Twenty eight patients who had not yet received medication for the present depressive episode (n=12) or had failed a single trial of an antidepressant medication (n=16) were started on sertraline and randomised to receive either real of sham HF-rTMS. HF-rTMS was applied to the left dorsolateral prefrontal area in daily sessions (30 trains of 2 s, 20-40 s intertrain interval, at 90% motor threshold) on 10 consecutive working days. The results suggest that in this patient population, HF-rTMS does not add efficacy over the use of standard antidepressant medication.
The information in this review suggests that there is no strong evidence for benefit from using transcranial magnetic stimulation to treat depression, although the small sample sizes do not exclude the possibility of benefit.