The International Journal of Neuropsychopharmacology

Review Article

Treatment-emergent mania in unipolar and bipolar depression: focus on repetitive transcranial magnetic stimulation

Guohua Xiaa1 c1, Prashant Gajwania1, David J. Muzinaa2, David E. Kempa1, Keming Gaoa1, Stephen J. Ganocya1 and Joseph R. Calabresea1

a1 Department of Psychiatry, Case Western Reserve University, Cleveland, OH, USA

a2 Department of Psychiatry and Psychology, Cleveland Clinic, Cleveland, OH, USA


This review focused on the treatment-emergent mania/hypomania (TEM) associated with repetitive transcranial magnetic stimulation (rTMS) treatment of depression. English-language literature published from 1966–2006 and indexed in Medline was searched. Ten of 53 randomized controlled trials on rTMS treatment of depression specifically addressed TEM. The pooled TEM rate is 0.84% for the active treatment group and 0.73% for the sham group. The difference is not statistically significant. Along with case reports, a total of 13 cases of TEM associated with rTMS treatment of depression have been published. Most of these patients were diagnosed with bipolar disorder and the majority of patients experiencing TEM took medication concurrent with rTMS. The parameters of rTMS used in these cases were scattered over the spectrum of major parameters explored in previous studies. Most train durations and intervals were within the published safety guidelines of the field. Reducing the frequency of sessions from two per day to one per day might be associated with a lower likelihood of TEM recurrence. The severity of manic symptoms varied significantly, but all cases responded to treatment that included a decrease or discontinuation of antidepressant and/or rTMS treatment and/or use of anti-manic medication. Current data suggests that rTMS treatment carries a slight risk of TEM that is not statistically higher than that associated with sham treatment. More systematic studies are needed to better understand TEM associated with rTMS. Special precautions and measures should be adopted to prevent, monitor, and manage TEM in research and practice.

(Received October 31 2006)

(Reviewed December 13 2006)

(Revised January 05 2007)

(Accepted January 29 2007)

(Online publication March 05 2007)


c1 Address for correspondence: G. Xia, M.D., Ph.D., NIMH Center for Bipolar Disorders, Department of Psychiatry, Case Western Reserve University, 11400 Euclid Ave, Suite 200, Cleveland, OH 44106, USA. Tel.: 216-844-2858 Fax: 216-844-2875 E-mail: