Vagus nerve stimulation therapy randomized to different amounts of electrical charge for treatment-resistant depression: Acute and chronic effects

Scott T. Aaronson, Linda L. Carpenter, Charles R. Conway, Frederick W. Reimherr, Sarah H. Lisanby, Thomas L. Schwartz, Francisco A. Moreno, David L. Dunner, Michael D. Lesem, Peter M. Thompson, Mustafa Husain, Craig J. Vine, Michael D. Banov, Lawrence P. Bernstein, Robert B. Lehman, Guy E. Brannon, George Keepers, John P. O'Reardon, Richard L. Rudolph, Mark Bunker

Research output: Contribution to journalArticle

60 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)631-640
Number of pages10
JournalBrain Stimulation
Volume6
Issue number4
DOIs
StatePublished - Jul 2013

Fingerprint

Treatment-Resistant Depressive Disorder
Vagus Nerve Stimulation
Therapeutics
Equipment and Supplies
Major Depressive Disorder
Double-Blind Method
Psychiatry
Depression
Safety

Keywords

  • Dose response
  • Treatment durability
  • Treatment-resistant depression
  • Vagus nerve stimulation
  • VNS efficacy

ASJC Scopus subject areas

  • Clinical Neurology
  • Neuroscience(all)
  • Biophysics

Cite this

Aaronson, S. T., Carpenter, L. L., Conway, C. R., Reimherr, F. W., Lisanby, S. H., Schwartz, T. L., ... Bunker, M. (2013). Vagus nerve stimulation therapy randomized to different amounts of electrical charge for treatment-resistant depression: Acute and chronic effects. Brain Stimulation, 6(4), 631-640. https://doi.org/10.1016/j.brs.2012.09.013

Vagus nerve stimulation therapy randomized to different amounts of electrical charge for treatment-resistant depression : Acute and chronic effects. / Aaronson, Scott T.; Carpenter, Linda L.; Conway, Charles R.; Reimherr, Frederick W.; Lisanby, Sarah H.; Schwartz, Thomas L.; Moreno, Francisco A.; Dunner, David L.; Lesem, Michael D.; Thompson, Peter M.; Husain, Mustafa; Vine, Craig J.; Banov, Michael D.; Bernstein, Lawrence P.; Lehman, Robert B.; Brannon, Guy E.; Keepers, George; O'Reardon, John P.; Rudolph, Richard L.; Bunker, Mark.

In: Brain Stimulation, Vol. 6, No. 4, 07.2013, p. 631-640.

Research output: Contribution to journalArticle

Aaronson, ST, Carpenter, LL, Conway, CR, Reimherr, FW, Lisanby, SH, Schwartz, TL, Moreno, FA, Dunner, DL, Lesem, MD, Thompson, PM, Husain, M, Vine, CJ, Banov, MD, Bernstein, LP, Lehman, RB, Brannon, GE, Keepers, G, O'Reardon, JP, Rudolph, RL & Bunker, M 2013, 'Vagus nerve stimulation therapy randomized to different amounts of electrical charge for treatment-resistant depression: Acute and chronic effects', Brain Stimulation, vol. 6, no. 4, pp. 631-640. https://doi.org/10.1016/j.brs.2012.09.013
Aaronson, Scott T. ; Carpenter, Linda L. ; Conway, Charles R. ; Reimherr, Frederick W. ; Lisanby, Sarah H. ; Schwartz, Thomas L. ; Moreno, Francisco A. ; Dunner, David L. ; Lesem, Michael D. ; Thompson, Peter M. ; Husain, Mustafa ; Vine, Craig J. ; Banov, Michael D. ; Bernstein, Lawrence P. ; Lehman, Robert B. ; Brannon, Guy E. ; Keepers, George ; O'Reardon, John P. ; Rudolph, Richard L. ; Bunker, Mark. / Vagus nerve stimulation therapy randomized to different amounts of electrical charge for treatment-resistant depression : Acute and chronic effects. In: Brain Stimulation. 2013 ; Vol. 6, No. 4. pp. 631-640.
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T1 - Vagus nerve stimulation therapy randomized to different amounts of electrical charge for treatment-resistant depression

T2 - Acute and chronic effects

AU - Aaronson, Scott T.

AU - Carpenter, Linda L.

AU - Conway, Charles R.

AU - Reimherr, Frederick W.

AU - Lisanby, Sarah H.

AU - Schwartz, Thomas L.

AU - Moreno, Francisco A.

AU - Dunner, David L.

AU - Lesem, Michael D.

AU - Thompson, Peter M.

AU - Husain, Mustafa

AU - Vine, Craig J.

AU - Banov, Michael D.

AU - Bernstein, Lawrence P.

AU - Lehman, Robert B.

AU - Brannon, Guy E.

AU - Keepers, George

AU - O'Reardon, John P.

AU - Rudolph, Richard L.

AU - Bunker, Mark

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N2 - 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.

AB - 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.

KW - Dose response

KW - Treatment durability

KW - Treatment-resistant depression

KW - Vagus nerve stimulation

KW - VNS efficacy

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