Low-frequency rTMS over right dorsolateral prefrontal cortex in the treatment of resistant depression: cognitive improvement is independent from clinical response, resting motor threshold is related to clinical response

Neuropsychobiology. 2012 Jun;65(4):227-35. doi: 10.1159/000336999. Epub 2012 May 25.


Background: Clinical studies have shown that repetitive transcranial magnetic stimulation (rTMS) is effective in a certain percentage of treatment-resistant depression (TRD). The left dorsolateral prefrontal cortex (DLPFC) 10 Hz rTMS stimulation received FDA approval in 2008, although different rTMS protocols have also shown their effectiveness in reducing depressive symptoms. We investigated the clinical, cognitive and neurophysiologic effects of a 3 weeks' protocol of low-frequency rTMS applied over the right DLPFC in resistant depression.

Methods: Twenty-eight patients with TRD (age range 28-55) received low-frequency rTMS (1 Hz) over the right DLPFC in a 3-week open trial. Hamilton scales for depression and anxiety, Corsi block-tapping test, phonemic verbal fluency, right and left resting motor thresholds were evaluated in each subject over the trial period.

Results: At the end of the trial 42.9% of the subjects were considered as responders. A significant reduction of both HAMD (p < 0.001) and HAMA (p < 0.01) total scores was observed. At the 3rd week, the performances in Corsi test (p < 0.02) and phonemic verbal fluency (p = 0.065) were improved independently from depressive symptoms variation. At the end of the rTMS protocol, a significantly decreased left hemisphere resting motor threshold was registered (p < 0.01), while right hemisphere resting motor threshold did not show significant variation.

Conclusion: Low-frequency rTMS over the right DLPFC appeared effective in 42.9% of depressive resistant subjects in this sample. A significant decrease in left hemisphere resting motor threshold was observed only in responders, while a trend for improvement in cognitive function has been found and appeared independent from clinical response.

MeSH terms

  • Adult
  • Cognition Disorders / etiology
  • Cognition Disorders / therapy
  • Depressive Disorder, Treatment-Resistant / complications*
  • Depressive Disorder, Treatment-Resistant / therapy*
  • Female
  • Functional Laterality*
  • Humans
  • Male
  • Middle Aged
  • Motor Activity / physiology*
  • Neuropsychological Tests
  • Prefrontal Cortex / physiology*
  • Psychiatric Status Rating Scales
  • Psychomotor Performance
  • Transcranial Magnetic Stimulation / methods
  • Treatment Outcome
  • Verbal Behavior