Augmentative repetitive navigated transcranial magnetic stimulation (rTMS) in drug-resistant bipolar depression


  • The authors of this paper do not have any affiliation or financial interest in any organization that might pose a conflict of interest in connection with this manuscript.

Bernardo Dell’Osso, M.D., Department of Psychiatry, University of Milan, Fondazione IRCCS Ospedale Maggiore Policlinico, Via F. Sforza 35, 20122 Milano, Italy. Fax: 0039 02 50320310; e-mail:


Objectives:  The efficacy of transcranial magnetic stimulation (TMS) has been poorly investigated in bipolar depression. The present study aimed to assess the efficacy of low-frequency repetitive TMS (rTMS) of the right dorsolateral prefrontal cortex (DLPFC) combined with brain navigation in a sample of bipolar depressed subjects.

Methods:  Eleven subjects with bipolar I or bipolar II disorder and major depressive episode who did not respond to previous pharmacological treatment were treated with three weeks of open-label rTMS at 1 Hz, 110% of motor threshold, 300 stimuli/day.

Results:  All subjects completed the trial showing a statistically significant improvement on the 21-item Hamilton Depression Rating Scale (HAM-D), Montgomery-Åsberg Depression Rating Scale, and Clinical Global Impression severity of illness scale (ANOVAs with repeated measures: = 22.36, p < 0.0001; = 12.66, p < 0.0001; and = 10.41, p < 0.0001, respectively). In addition, stimulation response, defined as an endpoint HAM-D score reduction of ≥50% compared to baseline, was achieved by 6 out of 11 subjects, 4 of whom were considered remitters (HAM-D endpoint score ≤ 8). Partial response (endpoint HAM-D score reduction between 25% and 50%) was achieved by 3/11 patients. No manic/hypomanic activation was detected during the treatment according to Young Mania Rating Scale scores (ANOVAs with repeated measures: = 0.62, p = 0.61). Side effects were slight and were limited to the first days of treatment.

Conclusions:  Augmentative low-frequency rTMS of the right DLPFC combined with brain navigation was effective and well tolerated in a small sample of drug-resistant bipolar depressive patients, even though the lack of a sham controlled group limits confidence in the results.