Emergence of mania in two middle-aged patients with a history of unipolar treatment-refractory depression receiving vagus nerve stimulation

OBJECTIVESWe report on two patients who experienced emergence of full manic symptoms while receiving vagal nerve stimulation (VNS).METHODSTwo patients, both with a well-documented and verified history of longstanding unipolar depression, were initiated on VNS for treatment of their severe major depressive episodes.RESULTSThe two patients had emergence of full manic symptoms after 8 and 9 months of VNS, respectively. Manic symptoms were adequately managed with standard treatments (mood stabilizer and electroconvulsive therapy) and VNS was continued in the two subjects for up to 5 years without any further occurrences of manic/hypomanic episodes.CONCLUSIONSThese cases suggest that some patients with treatment-resistant depression may have a previously unrecognized bipolar disorder, triggered only by VNS. This report also provides evidence that VNS-induced manic switches, however serious and troubling to patients, can be managed safely, and that VNS maintenance can be continued for an extended period of time without manic relapses. Although the mechanism of action of VNS is not known, emerging evidence supports central nervous system dopaminergic and possibly cholinergic system involvement.