Washington University School of Medicine Digital Commons@Becker Open Access Publications 2012 Marked response to VNS in a post-cingulotomy patient: Implications for the mechanism of action of VNS in TRD Charles R. Conway Washington University School of Medicine in St. Louis Mehret D. Gebretsadik Richard D. Bucholz St. Louis University Follow this and additional works at: https://digitalcommons.wustl.edu/open_access_pubs Recommended Citation Conway, Charles R.; Gebretsadik, Mehret D.; and Bucholz, Richard D., ,"Marked response to VNS in a post-cingulotomy patient: Implications for the mechanism of action of VNS in TRD." CNS Spectrums.16,6. 135-141. (2012). https://digitalcommons.wustl.edu/open_access_pubs/3300 This Open Access Publication is brought to you for free and open access by Digital Commons@Becker. It has been accepted for inclusion in Open Access Publications by an authorized administrator of Digital Commons@Becker. For more information, please contact [email protected]. CNS Spectrums http://journals.cambridge.org/CNS Additional services for CNS Spectrums: Email alerts: Click here Subscriptions: Click here Commercial reprints: Click here Terms of use : Click here Marked Response to VNS in a Post-Cingulotomy Patient: Implications for the Mechanism of Action of VNS in TRD Charles R. Conway, Mehret D. Gebretsadik and Richard D. Bucholz CNS Spectrums / Volume 16 / Issue 06 / June 2011, pp 135 - 141 DOI: 10.1017/S1092852912000302, Published online: 27 March 2012 Link to this article: http://journals.cambridge.org/abstract_S1092852912000302 How to cite this article: Charles R. Conway, Mehret D. Gebretsadik and Richard D. Bucholz (2011). Marked Response to VNS in a Post- Cingulotomy Patient: Implications for the Mechanism of Action of VNS in TRD. CNS Spectrums, 16, pp 135-141 doi:10.1017/S1092852912000302 Request Permissions : Click here Downloaded from http://journals.cambridge.org/CNS, IP address: 128.252.11.13 on 27 Sep 2014 doi: 10.1017/S1092852912000302 Review Article Marked Response to VNS in a Post-Cingulotomy Patient: Implications for the Mechanism of Action of VNS in TRD Charles R. Conway, MD, Mehret D. Gebretsadik MDc, and Richard D. Bucholz, MDd ABSTRACT FOCUS POINTS Treatment-resistant major depression (TRMD, • New, more invasive, treatments, (eg, vagus major depressive disorder that fails to respond nerve stimulation [VNS], deep brain stimulation), to numerous therapies) is a relatively common are evolving for the treatment of refractory ill- nesses in psychiatry. and clinically challenging disorder. In many cases, • VNS is Food and Drug Administration approved the most severely affected TRMD patients have for treatment augmentation in severe, treat- ment-refractory depression. Studies suggest that received surgical intervention (subcaudate trac- the antidepressant effects of VNS are typically totomy, limbic leucotomy, anterior capsulotomy, delayed by months. • Studies demonstrate that electroconvulsive ther- and anterior cingulotomy). New treatments, includ- apy (ECT) and VNS can be safely administered ing vagus nerve stimulation (VNS) and deep brain at the same time. Clinical experience and case stimulation, have emerged to treat individuals reports suggest that ECT and VNS may have synergistic effects, (ie, patients who responded with TRMD. We describe the case of a woman, 53 poorly to ECT in the past may respond better to years of age, with a long and sustained history this treatment after VNS implantation). of TRMD (33 years), which was unresponsive to numerous treatments (multiple pharmacothera- Her depression improved markedly, and it has pies, psychotherapy, electroconvulsive therapy remained in sustained remission for 3.5 years. [ECT]). Additionally, her TRMD failed to respond This case suggests a potential synergistic effect of to a bilateral anterior cingulotomy. She underwent VNS and ECT, as well as provides possible clues to placement of a cervical vagus nerve stimulator the neural circuitry of VNS in TRMD. and a brief course of ECT (3 unilateral treatments). Dr. Conway is associate professor in the Department of Psychiatry at Washington University School of Medicine; Director of the Washington University Treatment-resistant Depression and Neurostimulation Clinic; and assistant research professor in the Department of Neurology and Psychiatry at the St. Louis University School of Medicine in Missouri. Dr. Gebretsadik is a psychiatrist in private practice in Springfield, Missouri. Dr. Bucholz is KR professor of neuro- surgery in the Department of Surgery, Division of Neurosurgery at the St. Louis University School of Medicine; and Director of Neurosurgery Division, at the St. Louis University Department of Surgery. Faculty Disclosures: Dr. Conway has received honoraria for being on the speaker’s bureaus of Bristol-Myers Squibb, Merck, and Pfizer; and has received research support from Bristol-Myers Squibb. Mr. Gebretsakik and Mr. Bucholz report no affiliations with or financial interest in any organizations that may pose a conflict of interest. Date Submitted: March 31, 2010; Date Accepted: August 9, 2010; First published online: June 1, 201 1. Correspondence: Charles R. Conway, MD, 660 South Euclid, Campus Box 8134, St. Louis, MO 63110; E-mail [email protected] CNS Spectr 16:6 135 June 2011 Review Article INTRODUCTION ily history of depression, including a brother who Treatment-resistant major depression (TRMD) is committed suicide. She denied use of illicit drugs a variation of major depressive disorder in which but reported a history of alcoholism that was 8 patients fail to respond to numerous treatments years in sustained remission. Her medical history (typically antidepressants with augmentation strat- was remarkable for hypothyroidism (controlled), egies and psychotherapy).1 In many patients with fibromyalgia, epilepsy (controlled), and estro- TRMD, a variety of treatments, delivered singly or gen-replacement hormone therapy for oophorec- in combination, including pharmacotherapies, psy- tomy for uterine cancer. The patient began having chotherapies, and electroconvulsive therapy (ECT), seizures following a closed head trauma which fail to provide an adequate response. Psychiatry occurred at 46 years of age (her depression pre- has begun to explore more invasive treatments ceded her epilepsy). She reported an average of for TRMD, including vagus nerve stimulation 2 seizures/year (tonic-clonic) from 46–53 years of (VNS),2 which was approved by the Food and Drug age, and she reports that she does not recollect Administration as an adjunctive antidepressant her depression being any worse after the seizures therapy in 2005, and deep brain stimulation (DBS). than before. DBS has been approved for compassionate use Ms M’s pharmacotherapy treatment history for in obsessive-compulsive disorder and is currently TRMD was extensive. Over the previous 30 years, experimental for TRMD.3,4 In some severe cases, she had been treated with various combinations of surgical interventions are used, including subcau- 2–5 antidepressants and numerous augmentation date tractotomy, limbic leucotomy, anterior cap- agents. She had failed adequate dose-duration sulotomy, and anterior cingulotomy.5 Unlike VNS antidepressant trials with several different classes and DBS, these neurological surgeries involve cre- of antidepressant including selective serotonin ation of a lesion. In the case of a complete bilateral inhibitors (citalopram, paroxetine, fluvoxamine, cingulotomy (as described here), this lesion would and escitalopram), tricyclic antidepressants (imip- limit communication between the more anterior ramine, amitryptyline), serotonin-norepinephrine and posterior portions of the cingulum bundle. reuptake inhibitors (venlafaxine extended release, We describe the case of a TRMD patient whose duloxetine), buproprion, nefazodone, as well as depression did not respond to aggressive pharma- antidepressant augmentation trials with lithium, cotherapy, psychotherapy, bilateral anterior cingu- aripiprazole, and olanzapine. She had multiple lotomy, or ECT, but which remitted when treated courses of ECT (bilateral and unilateral) from with VNS in combination with ECT. 1970–2006, with generally limited immediate ben- efit and no sustained or long-term benefit. In 1981, CASE REPORT she underwent bilateral anterior cingulotomy for Ms M, a Caucasian woman, 53 years of age, TRMD, which had no effect on depressive symp- had TRMD of 33 years duration, and posttraumatic toms. She attempted suicide on several occasions stress disorder (PTSD) related to sexual trauma after the cingulotomy. In 1983 she underwent a that occurred around 20 years of age. Her depres- course of bilateral ECT (10 treatments) with no sion began in her early teens and resulted in response. Two years later, another course of 10 multiple psychiatric hospitalizations and several bilateral ECT treatments also failed. serious suicide attempts during her early twen- With regards to history of Diagnostic and ties. She denied being depression-free for >30 Statistical Manual of Mental Disorders, Fourth consecutive days, alternating between “severely Edition axis II pathology: none of her outpatient depressed” and “mildly depressed” for her records lists her as having an Axis II diagnosis. entire adult life. She had no history of psychosis Two psychiatric hospitalizations (1999 and 2000) or manic episodes. She reported limited anxiety listed the diagnosis of “borderline personality dis- symptoms, predominantly PTSD-related (recur- order”; a subsequent hospitalization