Vagus nerve stimulation for treatment-resistant depression: a randomized, controlled acute phase trial.
BACKGROUND
Vagus nerve stimulation (VNS) alters both concentrations of neurotransmitters or their metabolites and functional activity of central nervous system regions dysregulated in mood disorders. An open trial has suggested efficacy.


METHODS
This 10-week, acute, randomized, controlled, masked trial compared adjunctive VNS with sham treatment in 235 outpatients with nonpsychotic major depressive disorder (n = 210) or nonpsychotic, depressed phase, bipolar disorder (n = 25). In the current episode, participants had not responded adequately to between two and six research-qualified medication trials. A two-week, single-blind recovery period (no stimulation) and then 10 weeks of masked active or sham VNS followed implantation. Medications were kept stable. Primary efficacy outcome among 222 evaluable participants was based on response rates (>/=50% reduction from baseline on the 24-item Hamilton Rating Scale for Depression [HRSD(24)]).


RESULTS
At 10-weeks, HRSD(24) response rates were 15.2% for the active (n = 112) and 10.0% for the sham (n = 110) groups (p = .251, last observation carried forward [LOCF]). Response rates with a secondary outcome, the Inventory of Depressive Symptomatology - Self-Report (IDS-SR(30)), were 17.0% (active) and 7.3% (sham) (p = .032, LOCF). VNS was well tolerated; 1% (3/235) left the study because of adverse events.


CONCLUSIONS
This study did not yield definitive evidence of short-term efficacy for adjunctive VNS in treatment-resistant depression.
Rush
A John
AJ
Department of Psychiatry, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA. John.Rush@UTSouthwestern.edu
Marangell
Lauren B
LB
Sackeim
Harold A
HA
George
Mark S
MS
Brannan
Stephen K
SK
Davis
Sonia M
SM
Howland
Robert
R
Kling
Mitchel A
MA
Rittberg
Barry R
BR
Burke
William J
WJ
Rapaport
Mark H
MH
Zajecka
John
J
Nierenberg
Andrew A
AA
Husain
Mustafa M
MM
Ginsberg
David
D
Cooke
Robert G
RG
D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D000928:Antidepressive Agents / Q000627:therapeutic use; D001714:Bipolar Disorder / Q000628:therapy; D016022:Case-Control Studies; D003865:Major Depressive Disorder / Q000628:therapy*; D004351:Drug Resistance; D004599:Electric Stimulation Therapy; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D019964:Mood Disorders / Q000628:therapy; D011569:Psychiatric Status Rating Scales; D012016:Reference Values; D016896:Treatment Outcome; D014630:Vagus Nerve / Q000502:physiology / Q000528:radiation effects*
D000928:Antidepressive Agents