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

John P. O'Reardon, H. Brent Solvason, Philip G. Janicak, Shirlene Sampson, Keith E. Isenberg, Ziad Nahas, William M. McDonald, David Avery, Paul B. Fitzgerald, Colleen Loo, Mark A. Demitrack, Mark S. George, Harold A. Sackeim

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)1208-1216
Number of pages9
JournalBiological psychiatry
Volume62
Issue number11
DOIs
StatePublished - Dec 1 2007

Bibliographical note

Funding Information:
Dr. Avery has received grant support from the National Institute of Mental Health (NIMH) and Neuronetics; has acted as a consultant to Bristol Myers Squibb (BMS), Cyberonics, GlaxoSmithKline (GSK), Eli Lilly, Janssen, Pharmaceutica Products, Neuronetics, Performance Plus, and Takeda; and has been a member of speakers bureaus for BMS, Cyberonics, GSK, Eli Lilly, Janssen, and Pfizer. Dr. Demitrack is an employee of Neuronetics, the study sponsor, and owns equity in Lilly, Wyeth, and Neuronetics. Dr. Fitzgerald has received research support from Neuronetics. Dr. George has received grant support from Abbott, Cephos, Cortex, Cyberonics, Dantec, DarPharma, DARPA, GSK, Jazz, National Institutes of Health (NIH), NARSAD, Neotonus, NeuroPace, Neuronetics, and the Stanley Foundation; has acted as consultant to Abbott, Aspect Biomedical, Aventis, Jazz Pharmaceuticals, Argolyn Pharmaceuticals, Neuralieve, Neuronetics, and NeuroPace; and has been a member of speakers bureaus for Janssen, Lilly, GSK, Parke Davis, Picker Int, Cyberonics, and Mediphysics/Amersham. Dr. Isenberg has received grant support from NIMH and Neuronetics and has acted as a consultant to Wellpoint and Barnes Jewish-Christian Behavioral Health. Dr. Janicak has received grant support from Astra Zeneca, BMS, Janssen, Neuronetics, and Solvay; has acted as consultant to Astra Zeneca, BMS, Janssen, Neuronetics, and Shire; and is a member of speaker bureaus for Abbott, Astra Zeneca, BMS, Janssen, Pfizer, and Shire. Dr. Loo has received research support from National Health and Medical Research Council (Australia), Neuronetics, NSW Schizophrenia Fellowship, Pfizer Neuroscience Research Grant scheme, and Rebecca Cooper Medical Research Foundation. Dr. McDonald has received grant support from the American Foundation for Suicide Prevention, Fuqua Foundation, National Institute of Mental Health, National Institute of Neurological Disease and Stroke, National Alliance for Research in Schizophrenia and Depression, Neuronetics, and Janssen; has acted as consultant to Neuronetics, Janssen, Forest, BMS; has been a member of speakers bureaus for BMS, Forest, Janssen, and Solvay; and has equity in Amgen, Teva, Pfizer, and Abbott. Dr. Nahas has received grant support from Cyberonics, Eli Lilly, Integra, Medtronic, Neuronetics, NeuroPace, and NIMH; has acted as a consultant to Avanir Pharmaceutical, Aventis Pharmaceutical, Cyberonics, Neuronetics, and NeuroPace; and has been a member of the speakers bureau for Cyberonics. Dr. O’Reardon has received grant support from BMS, Cyberonics, Lilly, Magstim, Neuronetics, Pfizer, and Sanofi; acted as consultant for Lilly and Neuronetics; and is a member of speakers bureaus for BMS, Cyberonics, and Lilly. Dr. Sackeim has received research support from the Cyberonics, MECTA, National Alliance for Research in Schizophrenia and Depression, and NIMH and has acted as a consultant to Cyberonics, Eli Lilly, Magstim, MECTA, Neuronetics, NeuroPace, Novartis, and Pfizer. Dr. Sampson has received research support from Neuronetics and Pfizer and has acted as a consultant to NeuroPace. Dr. Solvason has received grant support from Astra Zeneca, BMS, Forest, GSK, and Neuronetics and has served as a consultant to Cephalon, Cyberonics, Forest, Lilly, NeuroPace, and Sepracor.

Funding Information:
Clinical trial is posted on www.clinicaltrials.gov . Listing No. NCT 00104611 . Supported by a grant from Neuronetics Inc.

Keywords

  • Clinical trial
  • TMS
  • efficacy
  • major depression
  • safety

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