@article{e082c0e8c91f43d080a0200d497dad80,
title = "Vagus nerve stimulation therapy randomized to different amounts of electrical charge for treatment-resistant depression: Acute and chronic effects",
abstract = "Background: Major depressive disorder is a prevalent, disabling, and often chronic or recurrent psychiatric condition. About 35% of patients fail to respond to conventional treatment approaches and are considered to have treatment-resistant depression (TRD). Objective: We compared the safety and effectiveness of different stimulation levels of adjunctive vagus nerve stimulation (VNS) therapy for the treatment of TRD. Methods: In a multicenter, double blind study, 331 patients with TRD were randomized to one of three dose groups: LOW (0.25 mA current, 130 μs pulse width), MEDIUM (0.5-1.0 mA, 250 μs), or HIGH (1.25-1.5 mA, 250 μs). A highly treatment-resistant population (>97% had failed to respond to ≥6 previous treatments) was enrolled. Response and adverse effects were assessed for 22 weeks (end of acute phase), after which output current could be increased, if clinically warranted. Assessments then continued until Week 50 (end of long-term phase). Results: VNS therapy was well tolerated. During the acute phase, all groups showed statistically significant improvement on the primary efficacy endpoint (change in Inventory of Depressive Symptomatology-Clinician Administered Version [IDS-C]), but not for any between-treatment group comparisons. In the long-term phase, mean change in IDS-C scores showed continued improvement. Post-hoc analyses demonstrated a statistically significant correlation between total charge delivered per day and decreasing depressive symptoms; and analysis of acute phase responders demonstrated significantly greater durability of response at MEDIUM and HIGH doses than at the LOW dose. Conclusions: TRD patients who received adjunctive VNS showed significant improvement at study endpoint compared with baseline, and the effect was durable over 1 year. Higher electrical dose parameters were associated with response durability.",
keywords = "Dose response, Treatment durability, Treatment-resistant depression, VNS efficacy, Vagus nerve stimulation",
author = "Aaronson, {Scott T.} and Carpenter, {Linda L.} and Conway, {Charles R.} and Reimherr, {Frederick W.} and Lisanby, {Sarah H.} and Schwartz, {Thomas L.} and Moreno, {Francisco A.} and Dunner, {David L.} and Lesem, {Michael D.} and Thompson, {Peter M.} and Mustafa Husain and Vine, {Craig J.} and Banov, {Michael D.} and Bernstein, {Lawrence P.} and Lehman, {Robert B.} and Brannon, {Guy E.} and Keepers, {George A.} and O'Reardon, {John P.} and Rudolph, {Richard L.} and Mark Bunker",
note = "Funding Information: The study was sponsored by Cyberonics, Inc., through contracts to investigating sites. Funding Information: Conflict of interest/financial disclosure statement: We declare the following financial relationships during the past two years: Dr. Aaronson has received consulting fees from Cyberonics, Neuronetics, Eli Lilly, and Genomind, lecture fees from Neuronetics, Eli Lilly, Sunovion, and AstraZeneca, and research support from the Dalio Family Foundation. Dr. Carpenter has served as an unpaid consultant to Neuronetics, received consulting fees from Abbott, Takeda-Lundbeck, Helicon, and Johnson & Johnson. She has received research support from NIMH, Cyberonics, Medtronic, NeoSync and Neuronetics. Dr. Conway has received grant support from a K08 NIMH Mentored Clinical Scientist Award, NARSAD Young Investigator Award, and Sidney Baer Foundation , research support from Bristol-Myers Squibb , and lecture fees from Merck, Bristol-Myers Squibb, Pfizer, and Sunovion. Dr. Reimherr has received research support from Cyberonics , GSK , Otsuka , Sunovion , Pfizer , Bristol-Myers Squibb, Novartis and Eli Lilly . He owns shares in Celgene. Dr. Lisanby has received research grants from Cyberonics, Neuronetics , Brainsway , ANS/St. Jude and NeoSync , equipment support from Magstim and Magventure, and holds patents on magnetic stimulation technology (not the focus of this manuscript). Dr. Schwartz has received research funding from Cyberonics, Teva (Cephalon) , and Bristol-Myers Squibb, consulting fees from PamLab, and Mylan (Dey). Dr. Moreno has received research support from Cyberonics. Dr. Dunner has received grant support from Cyberonics and Neuronetics, consulting fees from Eli Lilly, Cyberonics, Neuronetics, Cervel, Wyeth, Pfizer, and Jazz, and speaking fees from Pfizer, Wyeth, Neuronetics, AstraZeneca, and Bristol-Myers Squibb. Dr. Lesem has no disclosures to report. Dr. Thompson has received grant support from NIMH and DOD . Dr. Husain has received grant support from NIH /NIMH, NIDA , NINDS , NIA , NARSAD , Stanley Foundation , Cyberonics, Neuronetics, St. Jude Medical, MagStim (equipment only), Brainsway, and NeoSync . Dr. Vine has received consulting fees from, Eli Lilly, Forest, and Abbott. He has received honoraria from Eli Lilly, Pfizer, Forest, AstraZeneca, Wyeth, Shire, Janssen/Johnson and Johnson, GlaxoSmithKline, Somerset, Novartis and Merck. He has received grant/research support from SmithKline Beecham , Lilly Research Foundation , Organon , Janssen Research Foundation , Wyeth-Ayerst , Parke-Davis , Merck Research , and Cyberonics. Dr. Banov has received speaking fees from Eli Lilly, Pfizer, Bristol-Myers Squibb, Forest, Sunovion, and Merck. Dr. Bernstein has no disclosures to report. Dr. Lehman receives honoraria for promotional speaking from Merck, Shionogie, Purdue, Forest and Sunovion. Dr. Brannon has received research support from Sunovion , Merck , Novartis and Forest . Dr. Keepers has received research support from Cyberonics and Broaden . Dr. O'Reardon has received research support from Neosync. Dr. Rudolph was an employee (retired) and stockholder of Cyberonics. Dr. Bunker is an employee and stockholder of Cyberonics. ",
year = "2013",
month = jul,
doi = "10.1016/j.brs.2012.09.013",
language = "English (US)",
volume = "6",
pages = "631--640",
journal = "Brain Stimulation",
issn = "1935-861X",
publisher = "Elsevier Inc.",
number = "4",
}