• The primary outcome will be measured at 2 weeks, using depression scales scores : Hamilton depression rating scale, and Montgomery and Asberg Depression Rating Scale [ Time Frame: at 2 weeks ]
  

• Depressive psychomotor retardation will be assessed at 2 weeks [ Time Frame: at 2 weeks ]
  
• All depression measures will be assessed at 4 weeks, 2 weeks after the end of the trial to evaluate the lasting effects. [ Time Frame: at 4 weeks, 2 weeks after the end of the trial ]
  

The objectives of the study were :

• To localize the site of lowest frontal activity in each patient with resistant depression, using PET to measure regional cerebral metabolic rates for glucose (rCMRGlu).
• To demonstrate that high-frequency TMS (10Hz) guided on that site is more effective than standard or sham TMS, in resistant depressed patients, using a doubled blind controlled procedure.
• To assess the effects of TMS on regional cerebral metabolism using rCMRGlu PET after 10 sessions of TMS treatments.

Depressed patients meeting DSM-IV criteria for Major Depressive Disorder, aged between 18 and 55, have been included. They met criteria for depression resistant to antidepressant drugs They were randomised in 3 groups: guided prefrontal TMS, standard left prefrontal and sham left prefrontal TMS.

rTMS was administered daily on working days, for two weeks. Ten stimuli per second (10Hz) were applied in 20 courses so that patients received 1600 stimuli per day. Guided TMS was on a prefrontal target corresponding to the highest statistically significant hyperfunctional cluster determined with rCMRGlu PET. Standard stimulation was left pre-frontal, 5 cm anterior to the optimal stimulation point of the abductor pollices brevis. Stimulation strength was chosen at 90% relative to motor threshold. Sham rTMS used a procedure identical to the real standard treatment, but using a sham coil.