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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified October 2007 by Bayside Health.
Recruitment status was  Recruiting
Sponsor:
Collaborator:
National Health and Medical Research Council, Australia
Information provided by:
Bayside Health
ClinicalTrials.gov Identifier:
NCT00402220
First received: November 18, 2006
Last updated: October 30, 2007
Last verified: October 2007
  Purpose

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 Intervention
Major Depressive Disorder
Drug: TMS
Device: Sham TMS

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Double-Blind Sham Controlled Trial of rTMS in Treatment Resistant Major Depression

Further study details as provided by Bayside Health:

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

Estimated Enrollment: 120
Study Start Date: January 2007
Estimated Study Completion Date: January 2010
Arms Assigned Interventions
Active Comparator: 1
active TMS
Drug: TMS
Active Transcranial Magnetic Stimulation
Placebo Comparator: 2
Sham TMS
Device: Sham TMS
Sham Transcranial Magnetic Stimulation

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years to 85 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00402220

Contacts
Contact: Paul B Fitzgerald, MBBS, MPM, PhD, FRANZCP 9276 6564 p.fitzgerald@alfred.com.au

Locations
Australia, Victoria
Alfred Psychiatry Research Centre Recruiting
Prahran, Victoria, Australia, 3181
Sponsors and Collaborators
Bayside Health
National Health and Medical Research Council, Australia
Investigators
Principal Investigator: Paul B Fitzgerald, MBBS, MPM, PhD, FRANZCP Alfred Psychiatry Research Centre
  More Information

No publications provided

ClinicalTrials.gov Identifier: NCT00402220     History of Changes
Other Study ID Numbers: fitzgeraldp
Study First Received: November 18, 2006
Last Updated: October 30, 2007
Health Authority: Australia: Human Research Ethics Committee

Additional relevant MeSH terms:
Depression
Depressive Disorder
Depressive Disorder, Major
Behavioral Symptoms
Mood Disorders
Mental Disorders

ClinicalTrials.gov processed this record on September 18, 2014