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A randomized controlled trial with 4-month follow-up of adjunctive repetitive transcranial magnetic stimulation of the left prefrontal cortex for depression

  • A. Mogg (a1), G. Pluck (a1), S. V. Eranti (a1), S. Landau (a2), R. Purvis (a1), R. G. Brown (a3), V. Curtis (a4), R. Howard (a1), M. Philpot (a5) and D. M. McLoughlin (a1)...

Effectiveness of repetitive transcranial magnetic stimulation (rTMS) for major depression is unclear. The authors performed a randomized controlled trial comparing real and sham adjunctive rTMS with 4-month follow-up.


Fifty-nine patients with major depression were randomly assigned to a 10-day course of either real (n=29) or sham (n=30) rTMS of the left dorsolateral prefrontal cortex (DLPFC). Primary outcome measures were the 17-item Hamilton Depression Rating Scale (HAMD) and proportions of patients meeting criteria for response (⩾50% reduction in HAMD) and remission (HAMD⩽8) after treatment. Secondary outcomes included mood self-ratings on Beck Depression Inventory-II and visual analogue mood scales, Brief Psychiatric Rating Scale (BPRS) score, and both self-reported and observer-rated cognitive changes. Patients had 6-week and 4-month follow-ups.


Overall, Hamilton Depression Rating Scale (HAMD) scores were modestly reduced in both groups but with no significant group×time interaction (p=0.09) or group main effect (p=0.85); the mean difference in HAMD change scores was −0.3 (95% CI −3.4 to 2.8). At end-of-treatment time-point, 32% of the real group were responders compared with 10% of the sham group (p=0.06); 25% of the real group met the remission criterion compared with 10% of the sham group (p=0.2); the mean difference in HAMD change scores was 2.9 (95% CI −0.7 to 6.5). There were no significant differences between the two groups on any secondary outcome measures. Blinding was difficult to maintain for both patients and raters.


Adjunctive rTMS of the left DLPFC could not be shown to be more effective than sham rTMS for treating depression.

Corresponding author
*Address for correspondence: Dr D. M. McLoughlin, Section of Old Age Psychiatry, Box PO70, Institute of Psychiatry, King's College London, De Crespigny Park, London SE5 8AF, UK. (Email:
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DH Avery , PE Holtzheimer , W Fawaz , J Russo , J Neumaier , DL Dunner , DR Haynor , KH Claypoole , C Wajdik , P Roy-Byrne (2006). A controlled study of repetitive transcranial magnetic stimulation in medication-resistant major depression. Biological Psychiatry 59, 187194.

AT Barker , R Jalinous (1985). Non-invasive magnetic stimulation of human motor cortex. Lancet i (8437), 11061107.

S Eranti , A Mogg , G Pluck , S Landau , R Purvis , RG Brown , R Howard , M Knapp , M Philpot , S Rabe-Hesketh , R Romeo , J Rothwell , D Edwards , DM McLoughlin (2007). A randomized, controlled trial with 6-month follow-up of repetitive transcranial magnetic stimulation and electroconvulsive therapy for severe depression. American Journal of Psychiatry 164, 7381.

PB Fitzgerald , J Benitez , A de Castella , ZJ Daskalakis , TL Brown , J Kulkarni (2006). A randomized, controlled trial of sequential bilateral repetitive transcranial magnetic stimulation for treatment-resistant depression. American Journal of Psychiatry 163, 8894.

PB Fitzgerald , TL Brown , NAU Marston , ZJ Daskalakis , A de Castella , J Kulkarni (2003). Transcranial magnetic stimulation in the treatment of depression: a double-blind, placebo-controlled trial. Archives of General Psychiatry 60, 10021008.

MF Folstein , SE Folstein , PR McHugh (1975). ‘Mini mental state’: a practical method for grading the cognitive state of patients for the clinician. Journal of Psychiatric Research 12, 189198.

M Garcia-Toro , A Mayol , H Arnillas , I Capllonch , O Ibarra , M Crespi , J Mico , O Lafau , L Lafuente (2001). Modest adjunctive benefit with transcranial magnetic stimulation in medication-resistant depression. Journal of Affective Disorders 64, 271275.

MS George , SH Lisanby , HA Sackeim (1999). Transcranial magnetic stimulation – applications in neuropsychiatry. Archives of General Psychiatry 56, 300311.

L Grunhaus , PN Dannon , S Schreiber , OH Dolberg , R Amiaz , R Ziv , E Lefkifter (2000). Repetitive transcranial magnetic stimulation is as effective as electroconvulsive therapy in the treatment of nondelusional major depressive disorder. Biological Psychiatry 47, 314324.

A Hausmann , A Pascual-Leone , G Kemmler , CI Rupp , T Lechner-Schoner , K Kramer-Reinstadler , M Walpoth , S Mechtcheriakov , A Conca , EM Weiss (2004). No deterioration of cognitive performance in an aggressive unilateral and bilateral antidepressant rTMS add-on trial. Journal of Clinical Psychiatry 65, 772782.

LL Hermann , KP Ebmeier (2006). Factors modifying the efficacy of transcranial magnetic stimulation in the treatment of depression: a review. Journal of Clinical Psychiatry 67, 18701876.

F Koerselman , M Laman , H van Duijn , MAJ van Duijn , MAM Willems (2004). A 3-month, follow-up, randomized, placebo-controlled study of repetitive transcranial magnetic stimulation in depression. Journal of Clinical Psychiatry 65, 13231328.

FA Kozel , Z Nahas , C DeBrux , M Molloy , JP Lorberbaum , D Bohning , SC Risch , MS George (2000). How coil-cortex distance relates to age, motor threshold, and antidepressant response to repetitive transcranial magnetic stimulation. Journal of Neuropsychiatry and Clinical Neurosciences 12, 376384.

SH Lisanby , D Gutman , B Luber , C Schroeder , HA Sackeim (2001). Sham TMS: intracerebral measurement of the induced electrical field and the induction of motor-evoked potentials. Biological Psychiatry 49, 460463.

CK Loo , PB Mitchell (2005). A review of the efficacy of transcranial magnetic stimulation (TMS) treatment for depression, and current and future strategies to optimize efficacy. Journal of Affective Disorders 88, 255257.

C Loo , P Sachdev , H Esayed , B McDarmont , P Mitchell , M Wilkinson , G Parker , S Gandevia (2001). Effects of a 2-to 4-week course of repetitive transcranial magnetic stimulation (rTMS) on neuropsychologic functioning, electroencephalogram, and auditory threshold in depressed patients. Biological Psychiatry 49, 615623.

CK Loo , JL Taylor , SC Gandevia , BN McDarmont , PB Mitchell , PS Sachdev (2000). Transcranial magnetic stimulation (TMS) in controlled treatment studies: Are some ‘sham’ forms active? Biological Psychiatry 47, 325331.

DL Nyenhuis , RA Stern , C Yamamoto , T Luchetta , JE Arruda (1997). Standardization and validation of the Visual Analog Mood Scales. Clinical Neuropsychologist 11, 407415.

JE Overall , DR Gorham (1962). The brief psychiatric rating scale. Psychological Reports 10, 799812.

MG Palmieri , C Iani , A Scalise , MT Desiato , M Loberti , S Telera , MD Caramia (1999). The effect of benzodiazepines and flumazenil on motor cortical excitability in the human brain. Brain Research 815, 192199.

S Pridmore , JA Fernandes , Z Nahas , C Liberatos , MS George (1998). Motor threshold in transcranial magnetic stimulation: a comparison of a neurophysiological method and a visualization of movement method. Journal of ECT 14, 2527.

DO Rumi , WF Gattaz , SP Rigonatti , MA Rosa , F Fregni , MO Rosa , C Mansur , ML Myczkowski , RA Moreno , MA Marcolin (2005). Transcranial magnetic stimulation accelerates the antidepressant effect of amitriptyline in severe depression: a double-blind placebo-controlled study. Biological Psychiatry 57, 162166.

MH Trivedi , AJ Rush , SR Wisniewski , AA Nierenberg , D Warden , L Ritz , G Norquist , RH Howland , B Lebowitz , PJ McGrath , K Shores-Wilson , MM Biggs , GK Balasubramani , M Fava (2006). Evaluation of outcomes with citalopram for depression using measurement-based care in STAR*D: implications for clinical practice. American Journal of Psychiatry 163, 2840.

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Psychological Medicine
  • ISSN: 0033-2917
  • EISSN: 1469-8978
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