Repetitive transcranial magnetic stimulation (rTMS) has been recently FDA approved for the treatment of resistant depression. No accordance exists on which are the involved mechanisms of action and on which stimulation parameters, frequency and side are optimal.

To compare these different procedures we study patients with unipolar recurrent resistant major depressive disorder in a double-blind, controlled trial randomized to either sequential bilaterally on the right and left dorsolateral prefrontal cortex (DLPFC) or monolaterally on the right DLPFC. Patients will be randomized to receive sequentially low-frequency rTMS at 1 Hz to the right DLPFC and high-frequency rTMS at 10 Hz rTMS to the left DLPFC, or to receive low-frequency rTMS at 1 Hz to the right DLPFC. Significant antidepressant effect as expressed by a reduction of Hamilton Depression Scale score will be recorded in both the groups of patients.

Inclusion Criteria:

• Diagnostic and Statistical Manual-IV criteria for Depressive Major Episode Hamilton Rating Scale for Depression -28 (Ham-D)score ≥ 18
• Failure to respond to a minimum of two courses of antidepressant medications for at least 6 weeks

Exclusion Criteria:

• Any comorbid axis I disorder (except simple and social phobia)
• Any other significant medical, particularly neurologic, illnesses (seizures, head trauma and brain lesions)