Simultaneous Low (1 Hz)- and High (10 Hz)-Frequency Bilateral Transcranial Magnetic Stimulation in a Patient With Severe Depression and Crohn Disease Moacyr Alexandro Rosa, MD, PhD,*Þ Marco Aurelio Andrade, MD,*Þ Guilherme Lozi Abdo, MD,*Þ and Marina Odebrecht Rosa, MS, MDÞ Abstract: We present a case report in which electroconvulsive therapy had a good effect for the treatment of depression in association with Crohn disease, but adverse effects limited its use. Repetitive transcranial magnetic stimulation was tried both in a conventional way (high fre- quency over the left dorsolateral prefrontal cortex) and in a bilateral sequential way (high frequency in the same region followed in the same session by low frequency on the right side). Finally, bilateral simulta- neous stimulation (high frequency over the left and low frequency over the right side) was tried and resulted in a response similar to that of electroconvulsive therapy. Key Words: depression, Crohn disease, transcranial magnetic stimulation, ECT (J ECT 2012;28: e31Ye32) Dear Editor: In addition to medications, some other approaches are available for the treatment of severe and/or refractory depressive episodes, especially electroconvulsive therapy (ECT), and more recently, repetitive transcranial magnetic stimulation (rTMS). Electroconvulsive therapy is the most effective treatment avail- able, but its drawbacks are cognitive adverse effects and, less often, anesthesia-related issues. We report a case of severe de- pression associated with Crohn disease that did not respond well to an acute series of rTMS. She was treated with ECT with good response but had intolerance to anesthetic medications. Finally, she was offered, in a tentativeway, simultaneous bilat- eral rTMS, as no other option was readily available. CASE REPORT Our case patient was a 38-year-old single white woman who presented with depression associated with Crohn disease. Her symptoms began 8 years before and included sadness, irri- tability, insomnia, and anhedonia, combined with frequent liquid diarrhea and perianal fistulas. Major depression was diagnosed, and antidepressant medication was started with relatively good response. After 3 years, her father died, and depressive symp- toms were back with refractory characteristics, and even high doses and combinations of 2 or 3 different classes of anti- depressants and augmentation strategies did not work. She was offered a series of rTMS in addition to medication. Repetitive transcranial magnetic stimulation was started on a daily basis (excluding weekends) with a Nerosoft-MS (Neurosoft Ltd, Ivanovo, Russia). A figure-8 coil was used, with stimulus delivered to the left dorsolateral prefrontal cortex (DLPFC). Intensity was 100% of motor threshold, frequency was 10 Hz, train duration was 10 seconds, and intertrain interval was 20 seconds, with a total duration of session of 15 minutes (3000 pulses). After 17 treatments, she did not respond and started referring to suicidal ideation. Electroconvulsive therapy was then indicated. She re- ceived ECTon an outpatient basis. When treatment was initiated, she had excessive nausea (that could not be relieved with med- ication) related to the anesthetic drug (etomidate) during the sessions. Propofol was tried as an alternative, but seizure dura- tion dropped to 3 seconds and the efficacy of such short seizure was questioned. Despite adverse effects of the anesthesia, she received 8 sessions of ultrabrief right unilateral ECTs at 6 times her seizure threshold. Her depressive symptoms remitted, as well as her symptoms of Crohn disease. After being well for 4 months, she relapsed and had a suicide attempt (drug intake). The Crohn symptoms also relapsed. Electroconvulsive therapy was indicated once more, but she refused it, claiming that the adverse effect (intense nausea) was intolerable. With no more options left, we considered the possibility of a bilateral sequen- tial stimulation with rTMS. 1 We would stimulate the left DLPFC with high frequency (10 Hz), and then, at the same session, we would stimulate the right DLPFC with low frequency (1 Hz) and intensity of 100% motor threshold for 15 minutes. This paradigm was used for 1 week with no response; on the contrary, she was getting worse. With few other options to offer, we told her of the possibility of a simultaneous bilateral stimulation. She was aware of the novelty of the approach and the relatively scarce knowledge about it, and she gave a written consent, understand- ing that it was done in her best interest. Treatment was performed with 2 Nerosoft-MS devices. Two coils were positioned over the DLPFC with the help of a mechanic arm and would not interfere with one another. 2 The same parameters as the sequential treatment were used (high frequency to the left and low frequency to the right), except that they were given at the same time. After 5 days of treatment, she had remission of the symptoms. She received 5 more treat- ments. In the patient’s opinion, she was even better than when she remitted with ECT previously. Her Crohn symptoms dis- appeared altogether (to the point that she stopped all the medi- cations she was using for it). A maintenance approach was tried, with one treatment per week. She was doing fine after 5 months of follow-up. There were no adverse effects or complications during or in between the treatments. DISCUSSION The idea of stimulating both sides of the prefrontal cortex is not new. Actually, bilateral (and bifrontal, for that matter) ECT does that and is highly effective. Mechanisms of action may be different, though, as in rTMS, there is no seizure induction. BRIEF CLINICAL REPORT LETTER Journal of ECT & Volume 28, Number 3, September 2012 www.ectjournal.com e31 From the *Federal University of Sa ˜o Paulo, and †Instituto de Pesquisas Avanc ¸adas em Neuroestimulac ¸a ˜o (IPAN), Sao Paulo, Brazil. Received for publication February 22, 2012; accepted February 22, 2012. Reprints: Moacyr Alexandro Rosa, MD, PhD, Rua Vergueiro, 1855 cj. 46, Sa ˜o Paulo, SP, CEP 04101-000, Brazil (e-mail: moarosa@ipan.med.br). The authors have no conflicts of interest. Financial disclosures: Dr. Moacyr Alexandro Rosa is a paid consultant for Neurosoft do Brasil. Drs. Marco A. Andrade, Guilherme L. Abdo, and Marina O. Rosa have no financial disclosures. Copyright * 2012 by Lippincott Williams & Wilkins DOI: 10.1097/YCT.0b013e3182545187 Copyright © 2012 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.