| Study | Methods | Stimulation Parameters | Conclusions and Limitations |
|---|---|---|---|
| McNamara et al., 2001 | Number of trials:5 Avarage number of subjects per trial: 20-68 Total number of patients: 151 | Site: 3 left DLPC, 1 right DLPC, 1 bilateral stimulation Frequency:1-20 Hz | rTMS had beneficial effects on depression. There was insufficient evidence to evaluate effect of rTMS on mania and schizophrenia. The duration of the antidepressant effects could not be established. Small number of trials. Difficulty in blinding. |
| Holtzheimer et al., 2001 | Number of trials: 12 | Site: left and right DLPC (and sham) | rTMS was statistically superior to sham stimulation in the treatment of depression, showing a moderate to large effect size. The clinical significance of these results was modest. |
| Kozel and George, 2002 | Number of trials:12 Avarage number of subjects per trial: 6-35 Total number of patients: 230 | Duration: 2 studies of 1 week and 10 of 2 weeks Site: 12/12 left DLPFC Frequency: 0.3-20 Hz Intensity: 80-110% | There was a statistically significant evidence that left DLPFC rTMS stimulation was an acute antidepressant treatment. Limits: small number of subjects per trial, different parameters of stimulation, heterogeneity of the sample. |
| Martin et al., 2001 | Number of trials:16 Average number of subjects per trial: 19 | Duration: 1 or 2 weeks; | rPositive global effect (HDRS) in favor of highfrequency, left sided rTMS vs sham after 2 weeks. This positive effect disappeared when using the BDI scale. Small sample size. No description of method of concealment allocation used. Double-blind referred to patient outcome assessor. |
| Site: Left and right DLPFC, right DLPFC (and sham). | |||
| Burt et al., 2002 (first analysis) Open and uncontrolled TMS studies | Number of trials:13 Average number of subjects per trial: 16 Total number of patients: 208 | Duration: 1-3 weeks; | 9 studies reported quantitative change in depression scores (HRSD and MADRS) but their average reduction was only 37% and the degree of therapeutic change was relatively modest. It should not be assumed that all studies derived from the same population with the same characteristics. |
| Site: Vertex, left and right DLPFC, RF TMS, Motor area, bilateral DLPFC TMS; | |||
| Frequency: from 0,033 to 20 HZ; | |||
| Intensity: 80-130% or 1-2,5 T. | |||
| (second analysis) Randomized, controlled studies | Number of trials: 23 Average number of subjects per trial: 19 Total number of patients: 432 | Duration: 1-2 weeks; | Slow and fast rTMS seemed to have statistically superior antidepressant effects compared to sham but the magnitude of the effects was of doubtful clinical significance. The analysis of variance comparing slow and fast rTMS did not yield a significant between- class effect. |
| Site: Vertex, (frontal, temporal and parietal) left and right DLPFC (and sham); | |||
| Frequency: from 0,17 to 40 Hz; | |||
| Intensity: 80-110% or 0,015-1,9 T | |||
| (third analysis) Randomized trials comparing rTMS and ECT | Number of trials: 3 Average number of subjects per trial: 37 Total number of patients: 112 | Duration: 2-4-weeks; | The meta-analysis of the 3 rTMS/ECT comparisons favoured ECT but there was not a statistically significant advantage for ECT over rTMS, nor was there significant heterogeneity in effect size. The fact that this analysis is based only on 3 studies is a potential limitation. |
| Site: left DLPFC; | |||
| Frequency: 10-20 Hz; | |||
| Intensity: 90-100%. | |||
| Martin et al., 2003 | Number of trials: 14 Total number of patients: 394 | Duration: 1 or 2 weeks; | A significant advantage in favor of the active high frequency and left-sided treatment after two weeks (HRSD). Overall low methodological quality |
| Site: Left and right DLPFC (and sham). | |||
| Intensity: 80%-110%. | |||
| Couturier, 2005 | Number of trials: 6 Average number of subjects per trial: from 6 to 30; | Duration: 1-2 weeks; | Rapid-rate rTMS as efficacious as sham therapy in treating adults with a major depressive episode. Overall low statistical power. |
| Total number of patients: 91 | Site: left DLPFC (and sham); | ||
| Frequency: 10-20 Hz; | |||
| Intensity: 80-100%. | |||
| Herrmann et al., 2006 | Number of trials: 33 Total number of patients: 877 | Duration: 1 or more weeks, Site: left DLPFC (26/33) and right DLPFC (3/33) and bilateral stimulation. Frequency: less or more than 15 Hz Intensity: 80-100%. | rTMS was more effective than sham in the treatment of depression. No outcome predictor that clearly predicted rTMS efficacy was found. No significant bias were found. Limit: efficacy was examined only immediately after TMS treatment and not at follow-up. |
| Gross et al.. 2007 | Number of trials: 5 Average number of subject per trial: from 27 to 99 | Duration: 2-3 weeks; | Recent trials show larger antidepressant effect when compared to earlier meta-analysis. The number of sessions may be an important parameter to predict the clinical effect of rTMS. Small number of included studies. |
| Total number of patients: 274 | Site: left and right DLPFC, bilateral (and sham); | ||
| Frequency:1-15Hz Intensity: 90-110% | |||
| Lam et al. 2008 | Number of trials: 24 Average number of subjects per trial: from 10 to 301 Total number of patients: 1092 | Duration: 1-4 weeks; | Active rTMS was significantly superior to sham over short-term treatment of TRD (1-4 weeks) but the overall response and remission rates were low and it is unclear whether the effects were sustained. Different follow- up periods. |
| Site: Left and right DLPFC, bilateral (and sham); | |||
| Frequency: 1-20 Hz; | |||
| Intensity: 80-120% | |||
| Shutter, 2009 | Number of trials: 30 Total number of patients: 1164 | Duration: 1-4 weeks; | Active rTMS was significantly more efficacious than sham treatment. Treatment resistance or intensity of rTMS do not play a major role in the antidepressant effect |
| Site: Left DLPFC (and sham); | |||
| Frequency: 5-20 Hz; | |||
| Intensity: <100-120%. | |||
| Shutter, 2010 | Number of trials: 9 Average number of subject per trial:12-70 Total number of patients : 243 | Duration:1-3 weeks Site: vertex (1 study), left PFC (2 studies), right PFC(5 studies), bilateral PFC (1 study) Frequency:0.25-1 Hz Intensity: 90-110% | Slow frequency rTMS was more effective than sham in the treatment of MDD and as effective as fast frequency rTMS. There was no sufficient evidence to suppose the efficacy of slow-frequency bilateral stimulation. Limits: small number of studies, different target of stimulation used, |
| Slotema et al., 2010 | Numbers of trials: 40 (34 rTMS vs sham, 6 rTMS vs ECT) Avarage number of subject per trial: 6-301m Total number of patients: 1562 | Duration:1-5 weeks Site: left PFC (30 studies), right PFC (3 studies), bilateral PFC (7 studies) Frequency: 0.3-10 Hz Intensity: 80-120% | rTMS was more effective than sham treatment, but less than ECT. RTMS as monotherapy and low-frequency rightsided sTMS showed a trend toward better results. Limits: different definitions of “treatment resistant depression” were used in included studies. Several studies showed the number of dropout but not the reason. |
| Study | Methods | Stimulation Parameters | Conclusions and Limitations |
|---|---|---|---|
| McNamara et al., 2001 | Number of trials:5 Avarage number of subjects per trial: 20-68 Total number of patients: 151 | Site: 3 left DLPC, 1 right DLPC, 1 bilateral stimulation Frequency:1-20 Hz | rTMS had beneficial effects on depression. There was insufficient evidence to evaluate effect of rTMS on mania and schizophrenia. The duration of the antidepressant effects could not be established. Small number of trials. Difficulty in blinding. |
| Holtzheimer et al., 2001 | Number of trials: 12 | Site: left and right DLPC (and sham) | rTMS was statistically superior to sham stimulation in the treatment of depression, showing a moderate to large effect size. The clinical significance of these results was modest. |
| Kozel and George, 2002 | Number of trials:12 Avarage number of subjects per trial: 6-35 Total number of patients: 230 | Duration: 2 studies of 1 week and 10 of 2 weeks Site: 12/12 left DLPFC Frequency: 0.3-20 Hz Intensity: 80-110% | There was a statistically significant evidence that left DLPFC rTMS stimulation was an acute antidepressant treatment. Limits: small number of subjects per trial, different parameters of stimulation, heterogeneity of the sample. |
| Martin et al., 2001 | Number of trials:16 Average number of subjects per trial: 19 | Duration: 1 or 2 weeks; | rPositive global effect (HDRS) in favor of highfrequency, left sided rTMS vs sham after 2 weeks. This positive effect disappeared when using the BDI scale. Small sample size. No description of method of concealment allocation used. Double-blind referred to patient outcome assessor. |
| Site: Left and right DLPFC, right DLPFC (and sham). | |||
| Burt et al., 2002 (first analysis) Open and uncontrolled TMS studies | Number of trials:13 Average number of subjects per trial: 16 Total number of patients: 208 | Duration: 1-3 weeks; | 9 studies reported quantitative change in depression scores (HRSD and MADRS) but their average reduction was only 37% and the degree of therapeutic change was relatively modest. It should not be assumed that all studies derived from the same population with the same characteristics. |
| Site: Vertex, left and right DLPFC, RF TMS, Motor area, bilateral DLPFC TMS; | |||
| Frequency: from 0,033 to 20 HZ; | |||
| Intensity: 80-130% or 1-2,5 T. | |||
| (second analysis) Randomized, controlled studies | Number of trials: 23 Average number of subjects per trial: 19 Total number of patients: 432 | Duration: 1-2 weeks; | Slow and fast rTMS seemed to have statistically superior antidepressant effects compared to sham but the magnitude of the effects was of doubtful clinical significance. The analysis of variance comparing slow and fast rTMS did not yield a significant between- class effect. |
| Site: Vertex, (frontal, temporal and parietal) left and right DLPFC (and sham); | |||
| Frequency: from 0,17 to 40 Hz; | |||
| Intensity: 80-110% or 0,015-1,9 T | |||
| (third analysis) Randomized trials comparing rTMS and ECT | Number of trials: 3 Average number of subjects per trial: 37 Total number of patients: 112 | Duration: 2-4-weeks; | The meta-analysis of the 3 rTMS/ECT comparisons favoured ECT but there was not a statistically significant advantage for ECT over rTMS, nor was there significant heterogeneity in effect size. The fact that this analysis is based only on 3 studies is a potential limitation. |
| Site: left DLPFC; | |||
| Frequency: 10-20 Hz; | |||
| Intensity: 90-100%. | |||
| Martin et al., 2003 | Number of trials: 14 Total number of patients: 394 | Duration: 1 or 2 weeks; | A significant advantage in favor of the active high frequency and left-sided treatment after two weeks (HRSD). Overall low methodological quality |
| Site: Left and right DLPFC (and sham). | |||
| Intensity: 80%-110%. | |||
| Couturier, 2005 | Number of trials: 6 Average number of subjects per trial: from 6 to 30; | Duration: 1-2 weeks; | Rapid-rate rTMS as efficacious as sham therapy in treating adults with a major depressive episode. Overall low statistical power. |
| Total number of patients: 91 | Site: left DLPFC (and sham); | ||
| Frequency: 10-20 Hz; | |||
| Intensity: 80-100%. | |||
| Herrmann et al., 2006 | Number of trials: 33 Total number of patients: 877 | Duration: 1 or more weeks, Site: left DLPFC (26/33) and right DLPFC (3/33) and bilateral stimulation. Frequency: less or more than 15 Hz Intensity: 80-100%. | rTMS was more effective than sham in the treatment of depression. No outcome predictor that clearly predicted rTMS efficacy was found. No significant bias were found. Limit: efficacy was examined only immediately after TMS treatment and not at follow-up. |
| Gross et al.. 2007 | Number of trials: 5 Average number of subject per trial: from 27 to 99 | Duration: 2-3 weeks; | Recent trials show larger antidepressant effect when compared to earlier meta-analysis. The number of sessions may be an important parameter to predict the clinical effect of rTMS. Small number of included studies. |
| Total number of patients: 274 | Site: left and right DLPFC, bilateral (and sham); | ||
| Frequency:1-15Hz Intensity: 90-110% | |||
| Lam et al. 2008 | Number of trials: 24 Average number of subjects per trial: from 10 to 301 Total number of patients: 1092 | Duration: 1-4 weeks; | Active rTMS was significantly superior to sham over short-term treatment of TRD (1-4 weeks) but the overall response and remission rates were low and it is unclear whether the effects were sustained. Different follow- up periods. |
| Site: Left and right DLPFC, bilateral (and sham); | |||
| Frequency: 1-20 Hz; | |||
| Intensity: 80-120% | |||
| Shutter, 2009 | Number of trials: 30 Total number of patients: 1164 | Duration: 1-4 weeks; | Active rTMS was significantly more efficacious than sham treatment. Treatment resistance or intensity of rTMS do not play a major role in the antidepressant effect |
| Site: Left DLPFC (and sham); | |||
| Frequency: 5-20 Hz; | |||
| Intensity: <100-120%. | |||
| Shutter, 2010 | Number of trials: 9 Average number of subject per trial:12-70 Total number of patients : 243 | Duration:1-3 weeks Site: vertex (1 study), left PFC (2 studies), right PFC(5 studies), bilateral PFC (1 study) Frequency:0.25-1 Hz Intensity: 90-110% | Slow frequency rTMS was more effective than sham in the treatment of MDD and as effective as fast frequency rTMS. There was no sufficient evidence to suppose the efficacy of slow-frequency bilateral stimulation. Limits: small number of studies, different target of stimulation used, |
| Slotema et al., 2010 | Numbers of trials: 40 (34 rTMS vs sham, 6 rTMS vs ECT) Avarage number of subject per trial: 6-301m Total number of patients: 1562 | Duration:1-5 weeks Site: left PFC (30 studies), right PFC (3 studies), bilateral PFC (7 studies) Frequency: 0.3-10 Hz Intensity: 80-120% | rTMS was more effective than sham treatment, but less than ECT. RTMS as monotherapy and low-frequency rightsided sTMS showed a trend toward better results. Limits: different definitions of “treatment resistant depression” were used in included studies. Several studies showed the number of dropout but not the reason. |