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

NCT00402220 | Completed

• 1 other identifier: fitzgeraldp
• Study Type: interventional
• Target: 67
• Locations: 1 country
• Sites: 1

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.

Conditions

Major Depressive Disorder

Outcome Measures

Primary Outcomes (1)

• The 17- item Hamilton Rating Scale for Depression (HAM-D)

  every 3 weeks

Study Arms (2)

1

ACTIVE COMPARATOR

active TMS

Drug: TMS

2

PLACEBO COMPARATOR

Sham TMS

Device: Sham TMS

Interventions

TMS DRUG

Active Transcranial Magnetic Stimulation

1

Sham TMS DEVICE

Sham Transcranial Magnetic Stimulation

2

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients will be included if they:
• Have a DSM-IV diagnosis of a major depressive episode (SCID 11).
• Aged 18-85.
• 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.
• 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).
• Have had no increase or initiation of new antidepressant (or other psychoactive) therapy in the 4 weeks prior to screening.

You may not qualify if:

• Patients who have an unstable medical condition, neurological disorder or any history of a seizure disorder or are currently pregnant or lactating.
• In the opinion of the investigator, are a sufficient suicidal risk to require immediate electro-convulsive therapy.
• 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.

Sponsors & Collaborators

• Bayside Health: lead
• National Health and Medical Research Council, Australia: collaborator

Study Sites (1)

Alfred Psychiatry Research Centre

Prahran, Victoria, 3181, Australia

Location

MeSH Terms

Conditions

Depressive Disorder, Major

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders

Study Officials

• Paul B Fitzgerald, MBBS, MPM, PhD, FRANZCP

  Alfred Psychiatry Research Centre

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 18, 2006
• First Posted: November 22, 2006
• Study Start: March 1, 2007
• Primary Completion: January 1, 2011
• Study Completion: January 1, 2011
• Last Updated: October 19, 2020

Record last verified: 2020-10

Locations

AU (1)