A Double-blind Sham Controlled Trial of rTMS in Treatment Resistant Major Depression
Status:
Completed
Trial end date:
2011-01-01
Target enrollment:
Participant gender:
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.
Phase:
N/A
Details
Lead Sponsor:
Bayside Health
Collaborator:
National Health and Medical Research Council, Australia