Repetitive Transcranial Magnetic Stimulation and Treatment-emergent Mania and Hypomania: A Review of the Literature

Background: This review focuses on treatment-emergent mania/hypomania (TEM) associated with repetitive transcranial magnetic stimulation (rTMS). Methods: English-language studies involving possible rTMS-induced mania/hypomania published between 1966 and 2015 were retrieved through a Medline search using the search terms mania, hypomania, mixed affective state, treatment-emergent, repetitive transcranial magnetic stimulation, and rTMS. Fifteen case series and controlled studies describing TEM associated with rTMS treatment have been published involving 24 individuals, most of whomwere diagnosed with either bipolar I or II disorder or major depressive disorder. Results: rTMS has been shown to possibly induce manic or hypomanic episodes in patients with depression, who are sometimes also taking antidepressants. Both high-frequency and low-frequency rTMS with different stimulus parameters may be associated with TEM in both males and females. Conclusions: Given these findings, it is highly recommended that patients with bipolar disorder who are experiencing a depressive episode be prescribed a mood stabilizer and that patients diagnosed with major depressive disorder be reevaluated to consider the possibility that they might have bipolar disorder, before rTMS treatment is initiated. If TEM occurs, discontinuation of rTMS should be considered, while continuing mood-stabilizing medications. Further research is needed concerning the underlying neurobiological mechanisms and epidemiologic characteristics of TEM associated with rTMS.