Article

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

ABSTRACT

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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    • "Transcranial magnetic stimulation (TMS) is a safe and efficacious, noninvasive brain stimulation treatment for medication-resistant MDD. To date, the acute efficacy of TMS is supported by multiple double blind, randomized controlled trials [6] [7] [8] and a recent meta-analysis [9]. The ideal method for maintaining benefit for a patient who had an adequate response to an acute course of TMS has not been determined. "
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    ABSTRACT: Background: Repetitive transcranial magnetic stimulation (TMS) is efficacious for acute treatment of resistant major depressive disorder (MDD), but there is little information on maintenance TMS after acute response. Objective/hypothesis: This pilot feasibility study investigated 12-month outcomes comparing two maintenance TMS approaches - a scheduled, single TMS session delivered monthly (SCH) vs. observation only (OBS). Methods: Antidepressant-free patients with unipolar, non-psychotic, treatment-resistant MDD participated in a randomized, open-label, multisite trial. Patients meeting protocol-defined criteria for improvement after six weeks of acute TMS were randomized to SCH or OBS regimens. TMS reintroduction was available for symptomatic worsening; all patients remained antidepressant-free during the trial. Results: Sixty-seven patients enrolled in the acute phase, and 49 (73%) met randomization criteria. Groups were matched, although more patients in the SCH group had failed ≥2 antidepressants (p = .035). There were no significant group differences on any outcome measure. SCH patients had nonsignificantly longer time to first TMS reintroduction, 91 ± 66 days, vs. OBS, 77 ± 52 days; OBS patients were nonsignificantly more likely to need reintroduction (odds ratio = 1.21, 95% CI .38-3.89). Reintroduction lasted 14.3 ± 17.8 days (SCH) and 16.9 ± 18.9 days (OBS); 14/18 (78%) SCH and 17/27 (63%) OBS responded to reintroduction. Sixteen patients (32.7%) completed all 53 weeks of the study. Conclusions: Maintaining treatment-resistant depressed patients off medications with periodic TMS appears feasible in some cases. There was no statistical advantage of SCH vs. OBS, although SCH was associated with a nonsignificantly longer time to relapse. Those who initially respond to TMS have a strong chance of re-responding if relapse occurs.
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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. "
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    ABSTRACT: Major depressive disorder (MDD) is associated with a significant burden and costs to the society. As remission of depressive symptoms is achieved in only one-third of the MDD patients after the first antidepressant trial, unsuccessful treatments contribute largely to the observed suffering and social costs of MDD. The present article provides a summary of the therapeutic strategies that have been tested for treatment-resistant depression (TRD). A computerized search on MedLine/PubMed database from 1975 to September 2014 was performed, using the keywords “treatment-resistant depression”, “major depressive disorder”, “adjunctive”, “refractory” and “augmentation”. From the 581 articles retrieved, two authors selected 79 papers. A manual searching further considered relevant articles of the reference lists. The evidence found supports adding or switching to another antidepressant from a different class is an effective strategy in more severe MDD after failure to an initial antidepressant trial. Also, in subjects resistant to two or more classes of antidepressants, some augmentation strategies and antidepressant combinations should be considered, although the overall response and remission rates are relatively low, except for fast acting glutamatergic modulators. The wide range of available treatments for TRD reflects the complexity of MDD, which does not underlie diverse key features of the disorder. Larger and well-designed studies applying dimensional approaches to measure efficacy and effectiveness are warranted.
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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.
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