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.
Key Words
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References
- Modelling magnetic coil excitation of human cerebral cortex with a peripheral nerve immersed in a brain-shaped volume conductor: The significance of fiber bending in excitation.Electroencephalo Clin Neuro. 1992; 85: 291-301
- Tolerability and safety of high daily doses of repetitive transcranial magnetic stimulation in healthy young men.J ECT. 2006; 22: 49-53
- A controlled study of repetitive transcranial magnetic stimulation in medication-resistant depression.Biol Psychiatry. 2005; (September 1 [Epub ahead of publication])
- Changes in regional cerebral blood flow on recovery from depression.Psychol Med. 1995; 25: 247-261
- The anatomy of melancholia—focal abnormalities of cerebral blood flow in major depression.Psychol Med. 1992; 22: 607-615
- Regional brain metabolic changes in patients with major depression treated with either paroxetine or interpersonal therapy: preliminary findings [see comment].Arch Gen Psychiatry. 2001; 58: 631-640
- Neuropsychiatric applications of transcranial magnetic stimulation: A meta analysis.Int J Neuropsychopharmacol. 2002; 5: 73-103
- Efficacy of rapid-rate repetitive transcranial magnetic stimulation in the treatment of depression: A systematic review and meta-analysis [see comment].J Psychiatry Neurosci. 2005; 30: 83-90
- A comparison of mirtazapine and nortriptyline following two consecutive failed medication treatments for depressed outpatients: A STAR*D report.Am J Psychiatry. 2006; 163: 1161-1172
- Transcranial magnetic stimulation in the treatment of depression: A double-blind, placebo-controlled trial.Arch Gen Psychiatry. 2003; 60: 1002-1008
- Brain activity during transient sadness and happiness in healthy women.Am J Psychiatry. 1995; 152: 341-351
- SPECT and PET imaging in mood disorders.J Clin Psychiatry. 1993; 54: 6-13
- SPECT and PET imaging in mood disorders.J Clin Psychiatry. 1993; 54: 6-13
- A controlled trial of daily left prefrontal cortex TMS for treating depression [see comment].Biol Psychiatry. 2000; 48: 962-970
- Rapid-rate transcranial magnetic stimulation and ECT.Convuls Ther. 1994; 10 (discussion 255–258): 251-254
- Mood improvement following daily left prefrontal repetitive transcranial magnetic stimulation in patients with depression: A placebo-controlled crossover trial.Am J Psychiatry. 1997; 154: 1752-1756
- Daily repetitive transcranial magnetic stimulation (rTMS) improves mood in depression.Neuroreport. 1995; 6: 1853-1856
- The burden of recurrent depression: Causes, consequences, and future prospects.J Clin Psychiatry. 2001; 22: 5-9
- Using the international 10-20 EEG system for positioning of transcranial magnetic stimulation.Brain Topogr. 2003; 16: 95-99
- The navigation of transcranial magnetic stimulation.Psychiatry Res. 2001; 108: 123-131
- Symptom reduction and suicide risk in patients treated with placebo in antidepressant clinical trials: an analysis of the Food and Drug Administration database [see comment].Arch Gene Psychiatry. 2000; 57: 311-317
- Regional cerebral glucose utilization in patients with a range of severities of unipolar depression.Biol Psychiatry. 2002; 51: 237-252
- Therapeutic efficacy of right prefrontal slow repetitive transcranial magnetic stimulation in major depression: A double-blind controlled study [see comment].Arch Gen Psychiatry. 1999; 56: 315-320
- Meta-analysis of left prefrontal repetitive transcranial magnetic stimulation (rTMS) to treat depression.J Psychiatr Pract. 2002; 8: 270-275
- Size of treatment effects and their importance to clinical research and practice.Biological Psychiatry. 2006; 59: 990-996
- Double-blind controlled investigation of transcranial magnetic stimulation for the treatment of resistant major depression.Am J Psychiatry. 1999; 156: 946-948
- Effects of a 2- to 4-week course of repetitive transcranial magnetic stimulation (rTMS) on neuropsychologic functioning, electroencephalogram, and auditory threshold in depressed patients.Biol Psychiatry. 2001; 49: 615-623
- Transcranial magnetic stimulation for treating depression.Cochrane Database of Systematic Reviews. 2002; 2: CD003493
- Modulating limbic-cortical circuits in depression: Targets of antidepressant treatments.Sem Clin Neuropsychiatry. 2002; 7: 255-268
- Positron emission tomography imaging in depression: a neural systems perspective.Neuroimag Clin North Am. 2003; 13: 805-815
- Transcranial magnetic stimulation for depression and other psychiatric disorders [see comment].Psychol Med. 2001; 31: 1141-1146
- The Global Burden of Disease: A Comprehensive Assessment of Mortality and Disability from Diseases, Injuries and Risk Factors in 1990 and Projected to 2020.Harcourt University Press, Cambridge, MA1996
- Decreased regional brain metabolism after ECT.Am J Psychiatry. 2001; 158: 305-308
- Rapid-rate transcranial magnetic stimulation of left dorsolateral prefrontal cortex in drug-resistant depression [see comment].Lancet. 1996; 348: 233-237
- Motor threshold in transcranial magnetic stimulation: A comparison of a neurophysiological method and a visualization of movement method.J ECT. 1998; 14: 25-27
- Resistance to antidepressant medications and short-term clinical response to ECT [see comment].Am J Psychiatry. 1996; 153: 985-992
- Medication resistance and clinical response to electroconvulsive therapy.Psychiatry Res. 1990; 31: 287-296
- Comparison of mania and depression after brain injury: Causal factors.Am J Psychiatry. 1988; 145: 172-178
- Mood disorders in stroke patients: Importance of location of lesion.Brain. 1984; 107: 81-93
- the electric field induced during magnetic stimulation.in: Lecy W.J. Cracco R.Q. Barker A.T. Rothwell J. Magnetic Motor Stimulation: Basic Principles and Clinical Experience. Elsevier Science, Amsterdam1991: 268-278 (EEG Suppl. 43)
- A theoretical calculation of the electric field induced in the cortex during magnetic stimulation.Electroencephalo Clin Neuro. 1991; 81: 47-56
- Bupropion-SR, sertraline, or venlafaxine-XR after failure of SSRIs for depression.New Engl J Med. 2006; 354: 1231-1242
- Functional brain circuits in major depression and remission [comment].Arch Gen Psychiatry. 2001; 58: 649-650
- The definition and meaning of treatment-resistant depression.J Clin Psychiatry. 2001; 16: 10-17
- The impact of medication resistance and continuation pharmacotherapy on relapse following response to electroconvulsive therapy in major depression.J Clin Psychopharmacol. 1990; 10: 96-104
- Vagus nerve stimulation (VNS) for treatment-resistant depression: Efficacy, side effects, and predictors of outcome.Neuropsychopharmacology. 2001; 25: 713-728
- Remission rates following antidepressant therapy with bupropion or selective serotonin reuptake inhibitors: a meta-analysis of original data from 7 randomized controlled trials.J Clin Psychiatry. 2005; 66: 974-981
- Evaluation of outcomes with citalopram for depression using measurement-based care in STAR*D: Implications for clinical practice.Am J Psychiatry. 2006; 163: 28-40
- Risk and safety of repetitive transcranial magnetic stimulation: Report and suggested guidelines from the International Workshop on the Safety of Repetitive Transcranial Magnetic Stimulation, June 5–7, 1996.Electroencephalogr Clin Neurophysiol. 1998; 108: 1-16
Article info
Publication history
Published online: June 16, 2007
Accepted:
January 19,
2007
Received in revised form:
November 25,
2006
Received:
September 29,
2006
Identification
Copyright
© 2007 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
