• Change in depression symptoms, motor threshold, and hearing [ Time Frame: Measured at the end of Phases 1, 2, and 3 ] [ Designated as safety issue: Yes ]
• Safety and side effect data [ Time Frame: Measured daily throughout out treatment ] [ Designated as safety issue: Yes ]
• Neuropsychological changes [ Time Frame: Measured at the end of Phases 1 and 2 ] [ Designated as safety issue: Yes ]
• Quality of life [ Time Frame: Measured weekly throughout treatment ] [ Designated as safety issue: Yes ]

• Change in depression symptoms
• safety and side effect data
• neuropsychological changes
• quality of life

This study will evaluate the safety and effectiveness of magnetic brain stimulation for the treatment of major depression in depressed adults with moderate treatment resistance.

Major depression is a type of depression that can interfere with the ability to work, study, sleep, eat, and enjoy once pleasurable activities. Because people often develop resistances to medications used to treat depression, new treatments are needed. Decreased electrical activity in the prefrontal region of the brain has been linked to some symptoms of depression. Repetitive transcranial magnetic stimulation (rTMS) can be used to influence the brain's electrical activity. This procedure entails attaching electrodes to the head and using a device to pass magnetic energy through coils and into the brain. rTMS has been shown to have antidepressant effects in depressed individuals. However, optimal levels of intensity and treatment duration have yet to be determined. This study will assess the safety and effectiveness of rTMS on the prefrontal region of the brain in depressed adults with moderate treatment resistance.

The treatment phase of this double-blind study will last a minimum of 32 weeks and will consist of 3 phases. In Phase I, participants will be randomly assigned to receive either rTMS or sham stimulation. The sham stimulation will mimic the sensation of rTMS but will not induce an intracerebral current. Treatments will be administered daily for 3 weeks. Participants who show signs of improvement may continue Phase I for up to 3 additional weeks. In Phase II, participants who were unresponsive to Phase I treatment will receive daily rTMS at a lower dose for 3 weeks. Participants who show signs of improvement, but have not achieved remission, may continue Phase II for 4 additional weeks. Baseline magnetic resonance images will be used to determine the optimal stimulus intensity by adjusting for individual differences in cortical to skull distances. Phase III participants will be only those who achieved remission in the first 2 phases. These participants will receive antidepressant medication treatment daily for six months. Participants' functional status and symptoms of depression will be measured using self-report scales and video-recorded interviews at study start date and at the end of each treatment phase.

• Procedure: Prefrontal Repetitive Transcranial Magnetic Stimulation (rTMS)
• Drug: Antidepressant Regimen
• Procedure: Sham Stimulation
• Procedure: Lower Dose rTMS

• Experimental: Phase I participants receiving rTMS
• Placebo Comparator: Phase I participants receiving sham stimulation
• Experimental: Phase II participants
• Experimental: Phase III participants

Inclusion Criteria:

• Diagnosis of major depression with a current episode
• Hamilton Rating Scale for Depression score higher than 20
• No response or intolerance to antidepressant medication in the current depressive episode

Exclusion Criteria:

• Current use of antidepressants
• Diagnosis of psychosis or anxiety disorder
• Current substance abuse
• Seizures or history of head trauma