Transcranial magnetic stimulation accelerates the antidepressant effect of amitriptyline in severe depression: a double-blind placebo-controlled study

Biol Psychiatry. 2005 Jan 15;57(2):162-6. doi: 10.1016/j.biopsych.2004.10.029.


Background: Transcranial magnetic stimulation (TMS) is a noninvasive method to stimulate the cortex, and the treatment of depression is one of its potential therapeutic applications. Three recent meta analyses strongly suggest its benefits in the treatment of depression. The present study investigates whether repetitive TMS (rTMS) accelerates the onset of action and increases the therapeutic effects of amitriptyline.

Methods: Forty-six outpatients meeting DSM-IV criteria for nonpsychotic depressive episode were randomly assigned to receive rTMS (n = 22) or sham repetitive TMS (sham) (n = 24) during 4 weeks over dorsolateral prefrontal cortex (DLPFC) in this double-blind controlled trial. All patients were concomitantly taking amitriptyline (mean dose 110 mg/d). The rTMS group received 20 sessions (5 sections per week) of 5 Hz rTMS (120% of motor threshold and 1250 pulses per session). Sham stimulation followed the same schedule, however, using a sham coil. The efficacy variables were the Hamilton Depression Rating Scale-17 items (HAM-D/17), the Montgomery-Asberg Depression Rating Scale (MADRS), a Visual Analogue Scale (VAS), and the Clinical Global Impression (CGI). Tolerability was assessed by clinical examination and a safety screening of TMS side effects.

Results: Repetitive TMS had a significantly faster response to amitriptyline. There was a significant decrease in HAM-D/17 scores, already after the first week of treatment (p < .001 compared with baseline and p < .001 compared with sham). The decrease in HAM-D/17 scores in the rTMS group was significantly superior compared with the sham group throughout the study (p < .001 at fourth week).

Conclusions: Repetitive TMS at 5 Hz accelerated the onset of action and augmented the response to amitriptyline.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Amitriptyline / therapeutic use*
  • Analysis of Variance
  • Antidepressive Agents, Tricyclic / therapeutic use*
  • Chi-Square Distribution
  • Combined Modality Therapy
  • Depressive Disorder, Major / therapy*
  • Double-Blind Method
  • Electric Stimulation Therapy / methods
  • Electromagnetic Fields*
  • Female
  • Humans
  • Male
  • Prefrontal Cortex / physiopathology
  • Psychiatric Status Rating Scales
  • Transcranial Magnetic Stimulation / therapeutic use*
  • Treatment Outcome


  • Antidepressive Agents, Tricyclic
  • Amitriptyline