NHS Evidence Health Information Resources formerly National Library for Health

Transcranial magnetic stimulation is an effective treatment for depression, reported the Financial Times (30 November 2007). The newspaper accurately reported the results of a well conducted randomised controlled trial. The results appear reliable for the short-term treatment of major depression not alleviated by drug treatment.

The Financial Times (1) reported on 30 November 2007 that transcranial magnetic stimulation (TMS) is an effective and well-tolerated treatment for people with depression who have not benefited from previous treatments.
The reports were based on an RCT published in the journal Biological Psychiatry (2). A total of 325 people who had not responded to antidepressant medication were randomly assigned to receive active or sham treatment with TMS. After 4-6 weeks of treatment, changes in symptom scores and rates of response to treatment and remission of symptoms were significantly higher in the active treatment group on most measures. The primary outcome of the study was change from baseline on a depression rating scale and there was no significant difference between groups. Fewer than 5% of participants stopped treatment because of adverse events.
The newspaper accurately reported the main findings of the study. The study appears well conducted and the results appear reliable. As the participants included in the study were selected because their depression had not responded to previous treatment with antidepressant drugs they may therefore not be representative of the overall population of people with depression. Participants were treated for 4-6 weeks and the longer term effectiveness of TMS treatment was not evaluated.

Evaluation of the evidence base for TMS in the treatment of depression

Where does the evidence come from?

The evidence comes from an RCT involving 23 study sites in the USA, Australia and Canada. The research was led by Dr John O'Reardon of the University of Pennsylvania and funded by Neuronetics, Inc, a manufacturer of TMS equipment.

What were the authors' objectives?

To assess the efficacy and safety of TMS targeting the left dorsolateral prefrontal cortex in the short-term treatment of major depression.

What was the nature of the evidence?

This was an RCT involving 325 people with moderate to severe depression that had not responded to previous antidepressant drug treatment or who were unable to tolerate antidepressants.

What interventions were examined in the research?

Participants were randomly assigned to receive active or sham TMS therapy. Treatments were given daily in a 5-day sequence for a maximum of 30 sessions (six weeks), followed by tapering of treatment over three weeks and subsequent antidepressant medication. Equipment for sham TMS was identical to that used for active treatment but contained a magnetic shield that limited the magnetic energy reaching the cortex to 10% or less of the level in active treatment.

What were the findings?

Of the 325 randomised participants, 301 had at least one post-baseline assessment and were included in the analysis. The groups were similar at baseline except that the score on the Montgomery Asberg Depression Rating Scale (MADRS) was higher in the sham TMS group. The primary outcome of the study was change from baseline in MADRS and this did not differ significantly between groups in the main analysis. A supplementary analysis to take account of the baseline difference between groups showed a statistically significant result favouring active TMS. Changes in two other symptom scales significantly favoured active TMS at both four and six weeks. Response rates (50% improvement from baseline) significantly favoured active TMS on all three scales at 4 and 6 weeks. Differences in remission rates (achievement of a specific score) significantly favoured active TMS on two of the scales at six weeks. Overall discontinuation rates were 7.7% in the active TMS group and 8.2% in the sham TMS groups; discontinuations due to adverse events were 4.5% and 3.4%, respectively.

What were the authors' conclusions?

TMS is an effective treatment for major depression, with minimal adverse effects reported.

How reliable are the conclusions?

This was a generally well-conducted RCT, although the methods used for randomisation and concealing the treatment allocation sequence were not reported. Participants and outcome assessors were blinded to treatment allocation and the authors went to considerable lengths to make the active and sham treatments as similar as possible. Although the primary outcome did not show a significant difference between groups, the authors provided a justification for adjusting for the baseline difference in MADRS. Other outcome measures tended to support the conclusion that active TMS was more effective than sham treatment. The results of the study appear generally reliable but may not be generalisable to the wider population of people with depression or to treatment periods longer than 4-6 weeks.

Systematic reviews

Information staff at CRD searched for systematic reviews relevant to this topic. Systematic reviews are valuable sources of evidence as they locate, appraise and synthesize all available evidence on a particular topic.

There was one related systematic review identified on the Cochrane Database of Systematic Reviews (CDSR) (3) and four on the Database of Abstracts of Reviews of Effects (DARE) (4-7).

References and resources

1. Magnetic pulses ease depression. Financial Times, 30 November 2007, p8.

2. O’Reardon JP, Solvason HB, Janicak PG, Sampson S, Keith E. Isenberg KE, et al. Efficacy and safety of transcranial magnetic stimulation in the acute treatment of major depression: a multisite randomized controlled trial. Biological Psychiatry 2007;62(11):1208–16.

3. Martin JLR, Barbanoj MJ, Schlaepfer TE, Clos S, Perez V, Kulisevsky J, Gironell , A . Transcranial magnetic stimulation for treating depression. Cochrane Database of Systematic Reviews 2001, Issue 4. Art. No.: CD003493. DOI: 10.1002/14651858.CD003493.

4. Couturier J L. Efficacy of rapid-rate repetitive transcranial magnetic stimulation in the treatment of depression: a systematic review and meta-analysis. Journal of Psychiatry and Neuroscience 2005;30(2):83-90. [DARE Abstract]

5. Kozel F A, George M S. Meta-analysis of left prefrontal repetitive transcranial magnetic stimulation (rTMS) to treat depression. Journal of Psychiatric Practice 2002;8(5):270-75. [DARE Abstract]

6. Holtzheimer P E, Russo J, Avery D H. A meta-analysis of repetitive transcranial magnetic stimulation in the treatment of depression. Psychopharmacology Bulletin 2001;35(4):149-69. [DARE Abstract]

7. McNamara B, Ray J L, Arthurs O J, Boniface S. Transcranial magnetic stimulation for depression and other psychiatric disorders. Psychological Medicine 2001;31(7):1141-46. [DARE Abstract]