Efficacy of Repetitive Transcranial Magnetic Stimulation in the Prevention of Relapse of Depression

• Hamilton Depression Rating Scale [ Time Frame: baseline and 15 months ] [ Designated as safety issue: Yes ]
  Reduction on the scores of HDRS (as on the scores of Depression Scale and Hamilton Anxiety Scale; and improves the global clinical status in Clinical Global Impression, Global Assessment Scale and 36-item Short-form Health Survey - Quality of Life)
• Illness severity change [ Time Frame: baseline and 15 months ] [ Designated as safety issue: Yes ]
  Illness severity change as measured by Clinical Global Impression of Severity for depression.
• subject functioning [ Time Frame: baseline and 15 months ] [ Designated as safety issue: No ]
  Change in subject functioning using the Personal and Social Performance Scale (PSP)

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. Patients without previous exposure to rTMS will be given 4 to 6 days of rTMS for tolerability testing. Patients can continue their current antidepressant drugs through Day-1 (the day before the start of the study period). During the open-label periods, all patients will be treated with venlafaxine. Patients who meet pre-determined stabilization criteria will be eligible to enter the double-blind relapse prevention period and will be randomly assigned to either receive rTMS or placebo treatment. Efficacy will be evaluated during the study using a relapse assessment(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. Safety will be assessed throughout the study by monitoring of adverse events, clinical laboratory tests, electrocardiograms (ECGs), vital sign measurements (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.

• Procedure: repetitive Transcranial Magnetic Stimulation (rTMS)
  1 Hz; 360 impulsions; on period : 1 min; off period : 30 s.5 sessions per week for 4-6 weeks
• Behavioral: counseling
  Placebo monthly by general counseling for 12 months.

• Experimental: Repetitive Transcranial Magnetic Stimulation
  Intensity of 120% of individually determined motor threshold; frequency : 1 Hz; 360 impulsions; on period : 1 min; off period : 30 s.5 sessions per week for 4-6 weeks,than 2 sessions per week for 2 months, repeat that for 12 months.
  Intervention: Procedure: repetitive Transcranial Magnetic Stimulation (rTMS)
• Placebo Comparator: general counseling
  Placebo monthly by general counseling of doctors for 12 months.
  Intervention: Behavioral: counseling

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

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