None listed
Conditions
Brief summary
Major depressive disorder is a severe illness of high prevalence. A significant percentage of patients fail to respond to standard treatments and continue to experience marked disability and high morbidity. Repetitive transcranial magnetic stimulation (rTMS), which is a non-invasive means of stimulating nerve cells in superficial areas of the brain, is a promising therapy for those with treatment-resistant depression. Previous research conducted by our group clearly indicates that rTMS has antidepressant activity and that the response to rTMS is clinically meaningful in some patients. Whilst several forms of rTMS are clearly effective, no one type of rTMS has demonstrated markedly greater responses that other approaches. In recent years interest has developed into whether the dose of rTMS, in particular the number of pulses applied, is related to response to treatment (the percentage of patients that respond to treatment, the ‘response rate’). However, as there is a considerable time cost to higher dose protocols, their usefulness requires systematic evaluation. Therefore, the primary goal of this study is to examine whether response to rTMS is greater or more rapid when treatment is applied at a higher dose. To do this we will compare standard and high dose strategies for both low frequency rTMS applied to the right prefrontal cortex, and high frequency rTMS applied to the left prefrontal cortex. A secondary goal of the study is to explore potential predictors of antidepressant response to rTMS using brain imaging analysis.
Interventions
Repetitive Transcranial Magnetic Stimulation (rTMS).
TMS will be administered with a Medtronic Magpro30 magnetic stimulator using a 70mm figure-of-eight coil. Prior to the commencement of treatment TMS, single pulse TMS will be used to measure the resting motor threshold (RMT) for the abductor pollicis brevis (APB) in the right hand using standard methods.
Patients will be randomised into one of four treatment conditions:
1. High dose Low Frequency rTMS applied to the right prefrontal corte
Repetitive Transcranial Magnetic Stimulation (rTMS). TMS will be administered with a Medtronic Magpro30 magnetic stimulator using a 70mm figure-of-eight coil. Prior to the commencement of treatment TMS, single pulse TMS will be used to measure the resting motor threshold (RMT) for the abductor pollicis brevis (APB) in the right hand using standard methods. Patients will be randomised into one of four treatment conditions: 1. High dose Low Frequency rTMS applied to the right prefrontal cortex: Application of 2 continuous trains of 1 Hz rTMS of 30 minutes duration at 120% of the resting motor threshold (3600 pulses per session over 60 minutes). 2. High dose High Frequency rTMS applied to the left prefrontal cortex: Application of 125 trains of 10 Hz rTMS. 4.5 second trains will be applied at 120% of the resting motor threshold with a 15.5 second inter-train interval (5625 pulses per session over 41.6 minutes). 3. Standard dose Low Frequency rTMS applied to the right prefrontal cortex: Application of 1 continuous train of 1 Hz rTMS of 20 minutes duration at 120% of the resting motor threshold (1200 pulses per session over 20 minutes). 4. Standard dose High Frequency rTMS applied to the left prefrontal cortex: This will involve the application of 50 trains of 10 Hz rTMS. 4.5 second trains will be applied at 120% of the resting motor threshold with a 20.5 second inter-train interval (2250 pulses per session over 20.8 minutes). Each treatment will be administered for up to four weeks, five days per week (total of 20 treatment sessions). Patients will receive an assessment at baseline, 1, 2, 3 and 4 weeks (briefer assessments at weeks 1 and 3), and the primary study analysis will be based on this data. Patients may terminate treatment if they have responded at 2, 3 or 4 weeks. Patients who do not respond to one of the low dose treatment arms will be offered crossover treatment to the high dose condition using the opposite form of stimulation. Patients who do not respond to one of the high dose conditions will be offered the high dose form of stimulation applied to the opposite hemisphere. A subset of participants will also take part in a sub-study looking at potential predictors of response to rTMS treatment, involving participation in some computer-based tasks and MRI imaging.
Sponsors
Professor Paul Fitzgerald
Study design
Allocation
Randomised controlled trial
Primary purpose
Treatment
Masking
Blinded (masking used)
Eligibility
Sex/Gender
All
Age
18 Years to 80 Years
Healthy volunteers
Yes
Inclusion criteria
Patients with depression: 1. Have a DSM-IV diagnosis of a major depressive episode 2. Have failed to respond to adequate antidepressant medical therapy. This will be defined by at least two courses of antidepressant medication (from two medication classes) at therapeutic doses for a minimum of six weeks. Adequate daily dose will be considered to be a minimum of: 150mg of Imipramine or equivalent for tricyclic antidepressants, 20mg of Fluoxetine or equivalent for serotonin re-uptake inhibitors, 600mg of Moclobemide, 600mg of Nefazadone, 150mg of Venlafaxine, 60mg of Phenelzine or equivalent for monoamine oxidase inhibitors 3. Have a Hamilton Depression Rating Scale of > 16 (moderate – severe depression) 4. Have had no increase in, or initiation of new antidepressant therapy in the 4 weeks prior to screening. Healthy controls for the scanning sub study: 1. No personal history of psychiatric illness as determined via clinical interview.
Exclusion criteria
1. Have an unstable medical condition, neurological disorder or any history of a seizure disorder, or are currently pregnant or lactating For depression participants only: 2. In the opinion of the investigator, are at sufficient risk of suicide to require immediate ECT 3. Have a current DSM-IV diagnosis of substance abuse or dependence disorder, a diagnosis of a personality disorder or another Axis 1 disorder.
Outcome results
None listed