NCT00305045

Brief Summary

Studies exploring the efficacy of repetitive transcranial magnetic stimulation (rTMS) as a treatment for refractory major depressive disorder (MDD) have shown significant promise. Despite this, several questions regarding the treatment parameters needed to optimize efficacy remain. Moreover, there is also a lack of clear understanding as to the therapeutic mechanisms involved. For example, several lines of evidence suggest that patients with MDD have deficits in cortical inhibition (CI) and that these deficits are key to understanding the pathophysiology of this disorder. With this study, we seek to confirm the therapeutic potential of an acute course of rTMS for treatment-refractory MDD in a large sample of patients. In addition, we will strive to clarify the neurophysiological mechanisms through which rTMS exerts its therapeutic effects, using both TMS and electroencephalography/event related brain potential (EEG/ERP) measures of neurophysiological activity. Moreover, in this study, we intend to investigate the efficacy of a maintenance course of rTMS in an effort to prevent symptom recurrence.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
73

participants targeted

Target at P50-P75 for not_applicable major-depressive-disorder

Timeline
Completed

Started Mar 2005

Longer than P75 for not_applicable major-depressive-disorder

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

March 1, 2005

Completed
1 year until next milestone

First Submitted

Initial submission to the registry

March 19, 2006

Completed
2 days until next milestone

First Posted

Study publicly available on registry

March 21, 2006

Completed
3.1 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

May 1, 2009

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

May 1, 2009

Completed
Last Updated

January 24, 2012

Status Verified

January 1, 2012

Enrollment Period

4.2 years

First QC Date

March 19, 2006

Last Update Submit

January 23, 2012

Conditions

Major Depressive Disorder

Keywords

Major Depressive DisorderRepetitive Transcranial Magnetic StimulationTreatment resistance

Outcome Measures

Primary Outcomes (1)

  • Degree of change on the 17-item Hamilton Rating Scale for Depression (HAM-D)

    Weekly for 3 consecutive weeks. Select groups of subjects may be reassessed for an additional 3 to 52 weeks.

Study Arms (3)

High-frequency Left (HFL)

ACTIVE COMPARATOR

Intensity: rTMS treatment intensity determined by using resting motor threshold (RMT). Subjects under age 65 will have treatment delivered at 100% of the RMT; those over age 65 will have treatment delivered at 120% of the RMT. Site of Stimulation: left hemisphere of DLPFC. Frequency: 10 Hz. Duration: 29 - 5 second trains with 30 second inter-train interval.

Device: Repetitive Transcranial Magnetic Stimulation

Bilateral

ACTIVE COMPARATOR

Intensity: rTMS treatment intensity determined by using resting motor threshold (RMT). Subjects under age 65 will have treatment delivered at 100% of the RMT; those over age 65 will have treatment delivered at 120% of the RMT. Sites of Stimulation: right and left hemispheres of the DLPFC. Frequency: 1 Hz over the right DLPFC followed by 10 Hz over the left DLPFC. Duration: i) low-frequency right: 4 trains of 100 second duration and one train of 65 second duration, with a 30 second inter-train interval, followed by ii) HFL: 15 - 5 second trains with 30 second inter-train interval.

Device: Repetitive Transcranial Magnetic Stimulation

Sham Stimulation

SHAM COMPARATOR

Stimulation will occur over the site of active treatment, but with only the side-edge resting on the scalp. It will be administered as HFL for 17 minutes, with the coil angled 45 degrees away from the skull in a single-wing tilt position. This method produces sound and some somatic sensation (e.g., contraction of scalp muscles) similar to those of active stimulation, but with minimal direct brain effects.

Device: Repetitive Transcranial Magnetic Stimulation

Interventions

Repetitive Transcranial Magnetic StimulationDEVICE

Magnetic pulses to specified brain structures.

Also known as: MagPro X100 Series (Medtronic A/S, Copenhagen, Denmark)
BilateralHigh-frequency Left (HFL)Sham Stimulation

Eligibility Criteria

Age18 Years - 85 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • are voluntary and competent to consent based on their ability to provide a spontaneous narrative description of the key elements of the study (based on the MacCAT-CR)
  • have a Structured Clinical Interview for DSM-IV (SCID) confirmed DSM-IV diagnosis of MDD with no co-morbid borderline personality disorder and/or antisocial personality disorder, as confirmed by the Structured Clinical Interview for DSM-IV Axis II Disorders (SCID-II)
  • are between the ages of 18 and 85
  • have failed to achieve a clinical response to at least 2 separate antidepressant trials of sufficient dose for at least 6 weeks, according to Stage II criteria outlined by Thase et al., or could not tolerate at least 2 trials of antidepressant medication
  • have a score greater than or equal to 22 on the 17-item HAM-D
  • no major, unstable medical and/or neurological conditions, such as seizures, stroke, hypertension, diabetes, coronary artery disease, thyroid problems, respiratory illness, allergies and presence of metal implants.

You may not qualify if:

  • have a history of DSM-IV substance dependence in the last 6 months, and have DSM-IV substance abuse in the last month
  • history of self-harm behaviour in past 6 months
  • have a concomitant major, unstable medical or neurologic illness, or have had a history of seizures
  • are acutely suicidal
  • are pregnant
  • have metal implants
  • are currently (or in the last 4 weeks) taking: (1) more than lorazepam 2 mg daily (or equivalent); (2) monoamine oxidase inhibitors; and/or (3)bupropion due to its associated increased risk for seizures.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Centre for Addiction and Mental Health

Toronto, Ontario, M5T 1R8, Canada

Location

Related Publications (9)

  • Fitzgerald PB, Brown TL, Marston NA, Daskalakis ZJ, De Castella A, Kulkarni J. Transcranial magnetic stimulation in the treatment of depression: a double-blind, placebo-controlled trial. Arch Gen Psychiatry. 2003 Oct;60(10):1002-8. doi: 10.1001/archpsyc.60.9.1002.

    PMID: 14557145BACKGROUND

  • Klein E, Kreinin I, Chistyakov A, Koren D, Mecz L, Marmur S, Ben-Shachar D, Feinsod M. Therapeutic efficacy of right prefrontal slow repetitive transcranial magnetic stimulation in major depression: a double-blind controlled study. Arch Gen Psychiatry. 1999 Apr;56(4):315-20. doi: 10.1001/archpsyc.56.4.315.

    PMID: 10197825BACKGROUND

  • Grunhaus L, Schreiber S, Dolberg OT, Polak D, Dannon PN. A randomized controlled comparison of electroconvulsive therapy and repetitive transcranial magnetic stimulation in severe and resistant nonpsychotic major depression. Biol Psychiatry. 2003 Feb 15;53(4):324-31. doi: 10.1016/s0006-3223(02)01499-3.

    PMID: 12586451BACKGROUND

  • Sanacora G, Mason GF, Rothman DL, Hyder F, Ciarcia JJ, Ostroff RB, Berman RM, Krystal JH. Increased cortical GABA concentrations in depressed patients receiving ECT. Am J Psychiatry. 2003 Mar;160(3):577-9. doi: 10.1176/appi.ajp.160.3.577.

    PMID: 12611844BACKGROUND

  • Sanacora G, Mason GF, Krystal JH. Impairment of GABAergic transmission in depression: new insights from neuroimaging studies. Crit Rev Neurobiol. 2000;14(1):23-45. doi: 10.1615/critrevneurobiol.v14.i1.20.

    PMID: 11253954BACKGROUND

  • Sanacora G, Mason GF, Rothman DL, Krystal JH. Increased occipital cortex GABA concentrations in depressed patients after therapy with selective serotonin reuptake inhibitors. Am J Psychiatry. 2002 Apr;159(4):663-5. doi: 10.1176/appi.ajp.159.4.663.

    PMID: 11925309BACKGROUND

  • Trevizol AP, Goldberger KW, Mulsant BH, Rajji TK, Downar J, Daskalakis ZJ, Blumberger DM. Unilateral and bilateral repetitive transcranial magnetic stimulation for treatment-resistant late-life depression. Int J Geriatr Psychiatry. 2019 Jun;34(6):822-827. doi: 10.1002/gps.5091. Epub 2019 Apr 8.

    PMID: 30854751DERIVED

  • Weissman CR, Blumberger DM, Brown PE, Isserles M, Rajji TK, Downar J, Mulsant BH, Fitzgerald PB, Daskalakis ZJ. Bilateral Repetitive Transcranial Magnetic Stimulation Decreases Suicidal Ideation in Depression. J Clin Psychiatry. 2018 May/Jun;79(3):17m11692. doi: 10.4088/JCP.17m11692.

    PMID: 29701939DERIVED

  • Blumberger DM, Mulsant BH, Fitzgerald PB, Rajji TK, Ravindran AV, Young LT, Levinson AJ, Daskalakis ZJ. A randomized double-blind sham-controlled comparison of unilateral and bilateral repetitive transcranial magnetic stimulation for treatment-resistant major depression. World J Biol Psychiatry. 2012 Sep;13(6):423-35. doi: 10.3109/15622975.2011.579163. Epub 2011 Jul 8.

    PMID: 21736507DERIVED

Related Links

MeSH Terms

Conditions

Depressive Disorder, Major

Interventions

Transcranial Magnetic Stimulation

Condition Hierarchy (Ancestors)

Depressive DisorderMood DisordersMental Disorders

Intervention Hierarchy (Ancestors)

Magnetic Field TherapyTherapeutics

Study Officials

  • Zafiris J Daskalakis, MD, PhD

    Centre for Addiction and Mental Health

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
DOUBLE
Who Masked
PARTICIPANT, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
FACTORIAL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Director, Brain Stimulation Treatment and Research Program

Study Record Dates

First Submitted

March 19, 2006

First Posted

March 21, 2006

Study Start

March 1, 2005

Primary Completion

May 1, 2009

Study Completion

May 1, 2009

Last Updated

January 24, 2012

Record last verified: 2012-01

Locations

CA(1)