Hypomania Induction in a Patient With Bipolar II Disorder by Transcranial Direct Current Stimulation (tDCS) Vero ` nica Ga ´ lvez, MBBS,*Þþ§ Angelo Alonzo, BSC (Hons)/BA, PhD,*Þ Donel Martin, BSC (Hons), PhD,*Þ PhilipB. Mitchell, MBBS, MD, FRCPsych, FRANZCP,*Þ PerminderSachdev, MBBS, MD, PhD, FRANZCP,*|| and Colleen K. Loo, MBBS, MD, FRANZCP*Þ¶ Objectives: To report a case of hypomania induced by transcranial direct current stimulation (tDCS) given with an extracephalic reference electrode. Transcranial direct current stimulation is a noninvasive brain stimulation technique in which a weak current is applied through the scalp to produce changes in neuronal excitability in the underlying ce- rebral tissue. Recent clinical trials have shown promising results with left anodal prefrontal tDCS in treating depression. When the reference cathodal electrode in tDCS is moved from the cranium to an extrace- phalic position, larger areas of both cerebral hemispheres are stimu- lated, with potential implications for both efficacy and safety. Methods: We report the case of a 33-year-old female with bipolar II disorder, on mood stabilizer medication, who had previously participated in a clinical trial of tDCS given with a bifrontal electrode montage for the treatment of major depression without incident, but became hypo- manic when she received a later course of tDCS given with a fronto- extracephalic configuration. Factors contributing to the development of hypomania in the second course of tDCS are examined. Results: No substantial differences were found in the patient’s clinical presentation between the 2 tDCS courses to explain the emergence of hypomania only after the second course. The different montage used in the second course appeared to be the main contributory factor in the induction of hypomania. Conclusions: The reported case suggests that frontoextracephalic tDCS has antidepressant properties and the potential to induce hypomanic symptoms. In particular, it raises the question of whether frontoex- tracephalic tDCS requires additional precautions when administered to bipolar patients compared to bifrontal tDCS. Key Words: transcranial direct stimulation, extracephalic, depression, hypomania, bipolar disorder (J ECT 2011;00: 00Y00) W e report the case of a 33-year-old woman with diagno- sis of bipolar II disorder (BD II) who, despite being medicated with a mood stabilizer and having participated in a previous trial of anodal bifrontal transcranial direct current stimulation (tDCS) for the treatment of major depression (MD) without incident, experienced an episode of hypomania while participating in a trial of tDCS with an extracephalic reference electrode. Transcranial direct current stimulation is a noninvasive brain stimulation technique in which a weak current is applied through the scalp via electrodes to the underlying cerebral cortex, pro- ducing lasting changes in cortical excitability. 1 It has been shown to modulate the spontaneous neuronal firing, 2 with increased cor- tical excitability in regions under the anode and decreased excit- ability in regions under the cathode. 3,4 Of 3 recent double-blind placebo-controlled clinical trials, 2 of these found that anodal tDCS applied to the left dorsolateral prefrontal cortex (DLPFC) was more effective than sham stim- ulation in the treatment of depression. 5Y7 In these studies, the cathodal electrode was placed over the right supraorbital area, and antidepressant effects were attributed largely to left anodal pre- frontal stimulation. 6 Given the good safety profile of tDCS in these trials, we studied a more widely spaced electrode montage in an attempt to further increase the therapeutic efficacy of the technique. In this montage, the anode was maintained in the same left DLPFC anodal position, 7 but the cathodal electrode was placed extra- cephalically, on the contralateral arm, over the deltoid muscle (frontoextracephalic tDCS). Computer modeling has suggested that the latter montage would result in more widespread stimulation of cerebral areas than a bifrontal montage. 8 Given that modeling using a realistic head model found moderate activation in several deep structures (eg, hippocampus and amygdala) even with a bifrontal place- ment, 9 we hypothesize that it is highly likely that these areas were significantly activated with a frontoextracephalic montage and that this would enhance efficacy. Early tDCS studies had also trialed a frontoextracephalic montage (see Arul-Anandam and Loo 1 for review). Experiments performed by Redfearn et al 10 in depressed volunteers found that the largest alterations in affect were produced by a bifrontal- extracephalic configuration (2 electrodes above the eyebrows and an electrode on the right leg) rather than a bifrontal one. They theorized that stimulation of the brainstem and reticular activating system would be maximized with this configuration. Costain et al 11 performed a double-blind sham-controlled clin- ical trial with depressed individuals using the same bifrontal- extracephalic montage and found the clinical improvement in the active group to be significantly better than in the sham. To our knowledge, there is only one prior case report in the literature of mood switching with tDCS, 12 in which a 57-year- old man with a major depressive disorder experienced an episode of hypomania during a clinical trial with anodal bifrontal tDCS. CASE REPORT The case patient was a 33-year-old woman whose con- dition was diagnosed as BD II at the age of 30. She had a long CASE REPORT Journal of ECT & Volume 00, Number 00, Month 2011 www.ectjournal.com 1 From the *School of Psychiatry, University of New South Wales, Sydney, Australia; †Black Dog Institute, Sydney, Australia; ‡Mood Disorders Clinical and Research Unit, Psychiatry Department, Bellvitge University Hospital, L’Hospitalet de Llobregat, Barcelona, Spain; §Neuroscience Group, Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, Spain; ||Neuropsychiat- ric Institute, Sydney, Australia; and ¶St. George Hospital, Sydney, Australia. Received for publication August 30, 2010; accepted October 8, 2010. Reprints: Colleen K. Loo, MBBS, MD, FRANZCP, Black Dog Institute, Hospital Road, Randwick, 2031, Sydney, Australia (e-mail: Colleen.Loo@unsw.edu.au). This study was supported by Australian National Health and Medical Research Council (NHMRC) Project Grant No. 510142. The NHMRC had no further role in the study design; collection, analysis, and interpretation of data; writing of the report; and decision to submit the paper for publication. Copyright * 2011 by Lippincott Williams & Wilkins DOI: 10.1097/YCT.0b013e3182012b89 Copyright @ Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.