BACKGROUND: Major depressive disorder is a complex heterogeneous disorder. Treatment is especially challenging for patients with "difficult-to-treat depression" (DTD): a less stigmatizing and more clinically relevant framework defining depression that continues to cause significant burden despite usual treatment efforts.

METHODS: RESTORE-LIFE is a prospective, observational, multicenter, post-market study being conducted in Europe and is designed to reflect real-world clinical application of adjunctive Vagus Nerve Stimulation Therapy (VNS) for DTD. Baseline characteristics of RESTORE-LIFE patients were analyzed and compared to published treatment-resistant depression (TRD) trials.

RESULTS: This analysis includes the initial 98 RESTORE-LIFE patients who commenced treatment with VNS. Patients had a mean of 11.4 failed anti-depressant treatments, 1.1 suicide attempts, 87 % had prior electroconvulsive therapy, and 36 % had an endocrine/metabolic comorbidity. On average, disease severity was comparable to that in TRD trials (n = 15,463). However, RESTORE-LIFE patients appear to have been experiencing DTD for a longer duration and their DTD was characterized by a lack of positive mental health and meaningfulness of life, to a greater degree than by excess of negative mood. Despite high comorbidity rates in RESTORE-LIFE, VNS implantation was performed safely with no discontinuations due to surgical adverse events.

LIMITATIONS: RESTORE-LIFE enrolls any patient receiving adjunctive VNS for DTD. Prescription of VNS may be biased by differences in practices amongst sites and countries.

CONCLUSIONS: The present analysis offers insight into contemporary real-world use of VNS Therapy for DTD in Europe representing a comprehensive characterization of DTD and how this population may differ from those in the TRD literature.

Original languageEnglish
Pages (from-to)284-291
Number of pages8
JournalJournal of Affective Disorders
Early online date16 Oct 2023
Publication statusPublished - 1 Jan 2024


  • Humans
  • Vagus Nerve Stimulation/adverse effects
  • Depressive Disorder, Major/therapy
  • Depression
  • Prospective Studies
  • Treatment Outcome
  • Vagus Nerve/physiology


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