Efficacy and Safety of Transcranial Magnetic Stimulation in the Acute Treatment of Major Depression: A Multisite Randomized Controlled Trial

Department of Psychiatry, Columbia University, New York, New York, United States
Biological Psychiatry (Impact Factor: 10.26). 01/2008; 62(11):1208-16. DOI: 10.1016/j.biopsych.2007.01.018
Source: PubMed


We tested whether transcranial magnetic stimulation (TMS) over the left dorsolateral prefrontal cortex (DLPFC) is effective and safe in the acute treatment of major depression.
In a double-blind, multisite study, 301 medication-free patients with major depression who had not benefited from prior treatment were randomized to active (n = 155) or sham TMS (n = 146) conditions. Sessions were conducted five times per week with TMS at 10 pulses/sec, 120% of motor threshold, 3000 pulses/session, for 4-6 weeks. Primary outcome was the symptom score change as assessed at week 4 with the Montgomery-Asberg Depression Rating Scale (MADRS). Secondary outcomes included changes on the 17- and 24-item Hamilton Depression Rating Scale (HAMD) and response and remission rates with the MADRS and HAMD.
Active TMS was significantly superior to sham TMS on the MADRS at week 4 (with a post hoc correction for inequality in symptom severity between groups at baseline), as well as on the HAMD17 and HAMD24 scales at weeks 4 and 6. Response rates were significantly higher with active TMS on all three scales at weeks 4 and 6. Remission rates were approximately twofold higher with active TMS at week 6 and significant on the MADRS and HAMD24 scales (but not the HAMD17 scale). Active TMS was well tolerated with a low dropout rate for adverse events (4.5%) that were generally mild and limited to transient scalp discomfort or pain.
Transcranial magnetic stimulation was effective in treating major depression with minimal side effects reported. It offers clinicians a novel alternative for the treatment of this disorder.

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    • "After an important double-blind RCT suggesting efficacy of rTMS in treatmentresistant MDD [131], two multicenter rTMS trials were pivotal and consolidated rTMS use as a clinical (nonexperimental ) treatment. In one of them, O'Reardon et al. [132] evaluated 301 patients with treatment-resistant MDD without current antidepressant therapy. RTMS was applied over the left DLPFC at a 10Hz (120% motor threshold), 3000 pulses/day for 4-6 weeks. "
    Current Neuropharmacology 06/2015; 13(999):1-1. DOI:10.2174/1570159X13666150630173522 · 3.05 Impact Factor
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    • "One important limitation of this study is the three-arm design without a double-placebo arm. This design was used predominantly for ethical reasons as well as for the following reasons: previous studies have reported the superiority of LF rTMS compared to placebo [9] [13] and the non-inferiority of LF rTMS compared with venlafaxine [20]; and each of the approaches (rTMS and venlafaxine) has been reported to be more effective than a placebo in large RCTs (see, respectively [5] [6] and [32] [41] [42]). The authors acknowledge that their primary hypothesis could not be confirmed and that definite conclusions regarding the efficacy of LF rTMS in depression could not be drawn because of the lack of a placebo-medication and sham-TMS group. "
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    ABSTRACT: Context The aim of this study was to assess whether the combination of low frequency repetitive transcranial magnetic stimulation (rTMS) and venlafaxine (150-225 mg/day) is effective and safe for treatment-resistant unipolar depression (TRD). Method In a multicenter (18 centers) randomized double blind controlled trial with three arms, 170 patients were allocated to receive active rTMS combined with active venlafaxine (n= 55), active rTMS combined with placebo venlafaxine (n= 60) or sham rTMS combined with active venlafaxine (n= 55). The patients received once daily sessions of active or sham 1Hz rTMS applied over the right dorsolateral prefrontal cortex (360 pulses/day delivered at 120% of the resting motor threshold) for two to six weeks; rTMS was combined with active or sham venlafaxine (mean dose: 179.0 ± 36.6 mg/day). The primary outcome was the number of patients who achieved remission, which was defined as an HDRS-17 score < 8. Results We reported a similar significant antidepressant effect in the 3 groups (p< 10-6), with a comparable delay of action and a comparable number of remitters at the endpoint (28% in the combination group, 41% in the rTMS group and 43% in the venlafaxine group; p= 0.59). Conclusion Low frequency rTMS appears to be as effective as venlafaxine and as effective as the combination of both treatments for TRD. Because of its short session duration (the duration of one session was 8.5 minutes) and its safety, slow rTMS might be a useful alternative treatment for patients with TRD.
    Brain Stimulation 11/2014; 7(6). DOI:10.1016/j.brs.2014.07.040 · 4.40 Impact Factor
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    • "Our results could also have several implications for clinical applications, as it has been demonstrated the role of rTMS of the DLPFC in the treatment of major depressive disorder (MDD). This therapeutic effect can be achieved by either excitatory stimulation of the left (52, 55–57) or inhibitory stimulation of the right DLPFC (58–60). A recent meta-analysis study conducted by Chen and collaborators (20), demonstrated that, despite the comparable efficacy of both methodology, the latter (inhibitory TMS) may be a more acceptable treatment for MDD than the former (excitatory TMS), based on patients reporting less headaches, and on the decrease risk of inducing adverse events such as seizures (61). "
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    ABSTRACT: We combined continuous theta-burst stimulation (cTBS) and resting state (RS)-fMRI approaches to investigate changes in functional connectivity (FC) induced by right dorsolateral prefrontal cortex (DLPFC)-cTBS at rest in a group of healthy subjects. Seed-based fMRI analysis revealed a specific pattern of correlation between the right prefrontal cortex and several brain regions: based on these results, we defined a 29-node network to assess changes in each network connection before and after, respectively, DLPFC-cTBS and sham sessions. A decrease of correlation between the right prefrontal cortex and right parietal cortex (Brodmann areas 46 and 40, respectively) was detected after cTBS, while no significant result was found when analyzing sham-session data. To our knowledge, this is the first study that demonstrates within-subject changes in FC induced by cTBS applied on prefrontal area. The possibility to induce selective changes in a specific region without interfering with functionally correlated area could have several implications for the study of functional properties of the brain, and for the emerging therapeutic strategies based on transcranial stimulation.
    Frontiers in Psychiatry 08/2014; 5:97. DOI:10.3389/fpsyt.2014.00097
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