Repetitive Transcranial Magnetic Stimulation or Venlafaxine-Induced Mania?

To the Editor: In a recent issue of your journal, Chang et al.¹ reported aa manic episode in a 45-year-old man after a combined treatment of repetitive transcranial magnetic stimulation (rTMS) and venlafaxine. His manic symptoms were observed 4 weeks after the last rTMS session, while he was on venlafaxine 150 mg/day. Rapid rTMS applied over the left prefrontal cortex not only has antidepressant effect, but has been reported to produce manic switches.² In these case studies, manic or hypomanic switch appeared as early as the first session after starting rTMS or few days (maximum of 1 week) after rTMS treatment.² Further analysis of data revealed that treatment-emergent mania or hypomania occurred at a rate of 0.84% in the active rTMS treatment group, which was not significantly different from the sham group (0.73%).² Also, in a recent case study,³ hypomanic switch with transcranial DC stimulation occurred during treatment, after the third session.

Venlafaxine has been reported to induce mood-switching in patients with bipolar depression and in a few with unipolar depression.⁴ It is interesting to note that the time period from the introduction or the dose increment of venlafaxine to the induction of the manic or hypomanic episode ranged from 6 days to several weeks.⁴ Therefore, it is likely that the switch in the Chang et al.¹ case was due to venlafaxine, rather than rTMS treatment.