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A Double-Blind Sham Controlled Trial of rTMS in Treatment Resistant Major Depression

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00402220
Recruitment Status : Unknown
Verified October 2007 by Bayside Health.
Recruitment status was:  Recruiting
First Posted : November 22, 2006
Last Update Posted : October 31, 2007
National Health and Medical Research Council, Australia
Information provided by:
Bayside Health

Brief Summary:

The main treatment option for Treatment Resistant Depression is electroconvulsive therapy (ECT) which is often effective but complicated by cognitive side effects, need for anaesthesia and considerable stigma.

In recent years considerable efforts have been made to increase public awareness about depression and increase access to services. However, the increasing number of patients accessing treatment for depression in clinical services is also likely to be accompanied by a sizeable increase in the number of patients with TRD. Despite the demand, relatively few treatment options are available to such patients. One of the only substantially new treatments developed for TRD in recent years has been the advent of repetitive transcranial magnetic stimulation (rTMS). Repetitive TMS has been evaluated in over 20 trials conducted over the last 10 years. Previous research indicates that rTMS has antidepressant activity; however, the proportion of patients who respond to rTMS and the degree of treatment response demonstrated in trials to date is limited. The limitations of these studies include relatively small samples and limited duration of treatment (i.e., 2 weeks) as well as a lack of long term follow-up. As rTMS is gradually entering use in routine clinical practice (for example, recent regulation of its use in Canada), research is urgently required to establish ways to enhance treatment response both in regards to the extent of response within individuals and the proportion of individuals in whom rTMS has effects.

Stimulation site is another important treatment factor; thus far almost all of the trials of rTMS in TRD conducted have evaluated the utility of high frequency left prefrontal cortex (PFC) rTMS (HFL-TMS). In addition, several studies have evaluated the treatment efficacy of low frequency rTMS to right PFC (LFR-TMS). In a previously published study we have demonstrated that these two approaches have similar therapeutic benefit and both were superior to sham stimulation.

A promising new approach to enhance efficacy involves combining LFR-TMS and HFL-TMS in a sequential manner. We describe this as sequential bilateral rTMS (SB-rTMS). We have recently published the results of the first substantial evaluation of SB-rTMS showing not only a superiority to placebo in TRD but also a therapeutic response that is substantially superior to response rates in most of the published studies of unilateral rTMS (>50% of patients achieving standard criteria for clinical response compared to usually <30% in most studies). In this proposed research study, we will directly test the hypothesis that SB-rTMS produces a greater therapeutic response than HFL-TMS and compare both of these forms of stimulation to placebo (i.e., sham) stimulation.

Condition or disease Intervention/treatment Phase
Major Depressive Disorder Drug: TMS Device: Sham TMS Not Applicable

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 120 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Double-Blind Sham Controlled Trial of rTMS in Treatment Resistant Major Depression
Study Start Date : January 2007
Estimated Study Completion Date : January 2010

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Active Comparator: 1
active TMS
Drug: TMS
Active Transcranial Magnetic Stimulation

Placebo Comparator: 2
Sham TMS
Device: Sham TMS
Sham Transcranial Magnetic Stimulation

Primary Outcome Measures :
  1. The 17- item Hamilton Rating Scale for Depression (HAM-D) [ Time Frame: every 3 weeks ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 85 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

Patients will be included if they:

  1. Have a DSM-IV diagnosis of a major depressive episode (SCID 11).
  2. Aged 18-85.
  3. Have treatment resistant depression at Stage II of the Thase and Rush classification [31]; .e. have failed to achieve a clinical response, or did not tolerate, at least two separate antidepressant trials of sufficient dose for at least 6 weeks.
  4. Have a Hamilton Depression Rating Scale Score of > 20 (moderate - severe depression). Including only a severely ill group of subjects limits the placebo response rate [32]. Moreover, this will allow us to address the application of rTMS methods in the most clinically relevant subgroup of patients (in addition helping to constrain group heterogeneity, a major issue in depression research).
  5. Have had no increase or initiation of new antidepressant (or other psychoactive) therapy in the 4 weeks prior to screening.

Exclusion Criteria:

  1. Patients who have an unstable medical condition, neurological disorder or any history of a seizure disorder or are currently pregnant or lactating.
  2. In the opinion of the investigator, are a sufficient suicidal risk to require immediate electro-convulsive therapy.
  3. Have a current DSM IV diagnosis of substance abuse or dependence disorder, a diagnosis of a personality disorder (SCID II) or another axis 1 disorder.

Please note: several of these criteria (e.g. inclusion criteria 1 & 2, exclusion criteria 3) have been selected to explicitly constrain the heterogeneity of the sample to increase the likely power of the study to detect differences between the groups given the potentially subtle difference between the treatment methods.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00402220

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Contact: Paul B Fitzgerald, MBBS, MPM, PhD, FRANZCP 9276 6564

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Australia, Victoria
Alfred Psychiatry Research Centre Recruiting
Prahran, Victoria, Australia, 3181
Sponsors and Collaborators
Bayside Health
National Health and Medical Research Council, Australia
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Principal Investigator: Paul B Fitzgerald, MBBS, MPM, PhD, FRANZCP Alfred Psychiatry Research Centre
Layout table for additonal information Identifier: NCT00402220    
Other Study ID Numbers: fitzgeraldp
First Posted: November 22, 2006    Key Record Dates
Last Update Posted: October 31, 2007
Last Verified: October 2007
Additional relevant MeSH terms:
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Depressive Disorder
Depressive Disorder, Major
Mood Disorders
Mental Disorders