Vagus Nerve Stimulation: 2-Year Outcomes for Bipolar Versus Unipolar Treatment-Resistant Depression

Andrew A. Nierenberg, Jonathan E. Alpert, Erica E. Gardner-Schuster, Sheila Seay, David Mischoulon

Research output: Contribution to journalArticlepeer-review

66 Scopus citations


Background: The outcome of vagus nerve stimulation (VNS) for patients with bipolar treatment-resistant depression (TRD) has not been well characterized. This study describes the outcome of VNS for bipolar TRD patients participating in the acute and longitudinal pivotal trials and compares their outcome with unipolar TRD patients in the same trials. Methods: Of 235 participants enrolled in the acute study, 25 (11%) were diagnosed with DSM-IV bipolar I or II disorder. A sham-controlled 12-week trial of VNS preceded 2 years of open treatment. Bipolar and unipolar subjects were compared on baseline characteristics as well as acute and long-term outcomes. Results: At baseline, bipolar TRD was as severe as unipolar TRD but with depressive episodes of shorter duration and more failed antidepressant trials/year. Acute, 1-year, and 2-year outcomes were similar for both groups, even when the definition of response for bipolar TRD was expanded to include lack of manic symptoms. Conclusions: Bipolar TRD is a serious condition. In this hypothesis-generating analysis, VNS short- and long-term effects on bipolar and unipolar TRD were similar. Because these analyses were post hoc, these findings should not be interpreted as warranting clinical inference regarding effectiveness of VNS in patients with bipolar depression.

Original languageEnglish (US)
Pages (from-to)455-460
Number of pages6
JournalBiological Psychiatry
Issue number6
StatePublished - Sep 15 2008
Externally publishedYes


  • 2-year outcome
  • bipolar treatment-resistant depression
  • vagus nerve stimulation

ASJC Scopus subject areas

  • Biological Psychiatry


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