Elsevier

Biological Psychiatry

Volume 62, Issue 11, 1 December 2007, Pages 1208-1216
Biological Psychiatry

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

https://doi.org/10.1016/j.biopsych.2007.01.018Get rights and content

Background

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.

Methods

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.

Results

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.

Conclusions

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.

Section snippets

Subjects

Eligible subjects were antidepressant medication-free outpatients, aged 18–70, with a DSM-IV diagnosis of MDD, single episode or recurrent, with a current episode duration of 3 years or less. The episode had a Clinical Global Impressions Severity of Illness (CGI-S) score of at least 4 and a total score of at least 20 on the 17-item Hamilton Depression Rating Scale (HAMD17). Symptom stability was required during a 1-week no-treatment lead-in period, with a HAMD17 total score of at least 18 and a

Patient Disposition

Of the 325 patients randomized to TMS or sham, 301 (92.6%) had at least one postbaseline assessment, and their data comprised the a priori–specified analysis set. There were no baseline clinical or demographic differences between the 24 nonevaluable patients and the 301 evaluable subjects. Nonevaluable patients were evenly distributed between the active (n = 10) and the sham (n = 14) conditions, and there was no systematic difference between these groups in the reasons for discontinuation.

Discussion

This is the first large, multisite, randomized controlled trial of daily left prefrontal TMS in medication-free patients with major depression who had failed to receive adequate benefit from prior antidepressant treatment. The findings indicate that TMS, administered at these parameters for a period of 4–6 weeks, is safe and effective in the treatment of major depression.

The pattern of symptom improvement was consistent across the various study outcome measures. Active treatment with TMS was

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