Efficacy of Repetitive Transcranial Magnetic Stimulation in the Prevention of Relapse of Depression
Efficacy of Repetitive Transcranial Magnetic Stimulation in the Prevention of Relapse of Depression
The purpose of this study is to evaluate the efficacy of repetitive transcranial magnetic
 stimulation in the prevention of relapse of the symptoms of depression. Primary Outcome
 Measures:Time between subject randomization to treatment and the first occurrence of a
 relapse during the Relapse Prevention Period. Secondary Outcome Measures: Symptom change as
 measured by Hamilton Depression Rating Scale (HDRS); Illness severity change as measured by
 Clinical Global Impression of Severity for depression(CGI-S-DEP); Change in subject
 functioning using the Personal and Social Performance Scale.
Transcranial magnetic stimulation is a noninvasive technique that can influence specific
 areas of the brain and has very few side effects.Several factors characterize repetitive
 transcranial magnetic stimulation (rTMS) as a strategic aid in the treatment of
 depression.Depression is a chronic illness and generally requires life-long treatment.
 However, up to current days there have been no studies evaluating the effects of rTMS in the
 maintenance treatment of depression. This is a randomized, double-blind, placebo-controlled,
 parallel-group, multicenter study to evaluate the efficacy of rTMS, as monotherapy, relative
 to placebo in delaying the time to relapse in patients with depression. Patients with acute
 symptoms of depression will be enrolled. The study will consist of 4 periods: an up to 7 days
 screening/tolerability period, a 6-week open-label flexible dose lead-in period, a 6-week
 open-label fixed dose stabilization period, and a 12 months double-blind relapse prevention
 period. The study will consist of 4 phases: a screening/tolerability phase of up to 7 days;
 an open-label, flexible-dose lead-in phase of 8 weeks; an open-label, fixed-dose
 stabilization phase of 6 weeks; and a single-blind relapse prevention phase of 12 months.
 During the open-label phase, all patients will be treated with venlafaxine. Remitterswith
 Hamilton Rating Scale for Depression [HAM-D17] score ≤ 7will be eligible to enter the
 single-blind phase and will be randomly assigned to one of three groups: group 1 on active
 rTMS and venlafaxine; group 2 on sham rTMS and venlafaxine; group 3 on venlafaxine alone.
 Efficacy will be evaluated during the study using relapse assessment (time between subject
 randomization to treatment and the first occurrence of relapse). Secondary outcome measures
 will include: symptom changes, measured by the Hamilton Rating Scale for Depression
 [HAM-D17]; illness severity changes, measured by the Clinical Global Impression of Severity
 for Depression (CGI-S-DEP); and changes in subject functioning, assessed with the Personal
 and Social Performance Scale. Safety will be assessed throughout the study by monitoring of
 adverse events, clinical laboratory tests, electrocardiography, and measurements of vital
 signs (temperature, pulse and blood pressure) and weight. Suicidality will be assessed by the
 Columbia Suicide Severity Rating Scale (C-SSRS). A 10 milliliter pharmacogenomic blood sample
 (sample for DNA research) will be collected from patients who give separate written informed
 consent for this part of the study.
Inclusion Criteria:

 -  DSM-IV diagnosis of depression

 -  Experiencing an acute exacerbation of depression symptoms

 -  Baseline score of at least 14 points on the Hamilton Depression rating Scale-17 items

 -  Healthy based on physical examinations, electrocardiogram (ECG), laboratory tests,
 medical history, and vital signs measurements

 Exclusion Criteria:

 -  Comprised ferromagnetic metallic implants

 -  Pacemakers

 -  Previous neurosurgery

 -  History of seizures

 -  Major head trauma

 -  Alcoholism

 -  Drug addiction

 -  Any psychiatric or neurological disorder other than depression and anxiety

 -  Psychotic depression

 -  Suicidal propensities