690. Impact of VNS on symptoms, function, and quality of life in patients with markedly treatment-resistant depression: findings from the US RECOVER study

Abstract

Abstract Background Treatment-resistant depression (TRD), characterized by marked symptom burden and poor daily function and quality of life (QoL), remains a major clinical challenge. Greater degrees of treatment resistance (more failed trials) are associated with lower rates of initial benefit and higher rates of relapse. Vagus nerve stimulation (VNS) offers potential benefits by delivering intermittent electrical pulses to the left cervical vagus nerve through a surgically implanted device. Although VNS was approved by the US Food and Drug Administration for TRD in 2005, the Centers for Medicare & Medicaid Services (CMS) declined coverage for this treatment in 2007. Following publications of VNS registry data showing benefits of VNS, LivaNova, in collaboration with CMS, launched RECOVER (NCT03887715) in 2019. Aims & Objectives To evaluate the short- and long-term safety and efficacy of adjunctive VNS with treatment as usual in adults with markedly TRD. Method RECOVER is a multicenter, triple-blind, randomized, controlled trial (RCT). Enrolled participants had moderate-to-severe depressive disorder and had failed ≥4 adequate antidepressant treatments in the current episode. Participants were randomized 1:1 to receive adjunctive active or sham VNS during an initial 12-month RCT phase, after which all participants received active adjunctive VNS for an additional 4 years. Clinical outcomes were assessed every month over the 12-month RCT phase and then every 6 months during the long-term extension. QoL and function were assessed quarterly during the RCT phase and then every 6 months thereafter. Results Altogether, 88.4% of participants (N=493) with markedly treatment-resistant (13.3 mean lifetime failed treatments) and chronic (29.4 mean years depressed) major depressive disorder completed the trial’s RCT phase. There was no between-group difference in percent time in response with the primary outcome, the Montgomery-Åsberg Depression Rating Scale (MADRS), though there was with the Quick Inventory of Depressive Symptomatology–Self-Report (QIDS-SR) (25.2% vs 19.8%; P=0.049) and the Clinical Global Impression–Improvement (CGI-I) (26.7% vs 18.2%; P=0.004). For partial response (at least a 30% reduction from baseline), the clinician-rated QIDS (QIDS-C) (39.6% vs 30.7%; P=0.006) and the CGI-I (53.8% vs 39.8%; P<0.001) also distinguished the groups, as did daily function (Work Productivity and Activity Impairment questionnaire item 6: 43.3% vs 37.5%; P=0.039) and QoL (Mini Quality of Life Enjoyment and Satisfaction Questionnaire: 45.4% vs 37.1%; P=0.011). A tripartite metric combining these 3 outcome domains (P=0.005) significantly favored active stimulation over sham. Over 80% of participants who achieved clinically meaningful benefit after 12 months of active VNS in symptom, function, or QoL measures retained these benefits at 18- and 24-month assessments, demonstrating remarkable durability in participants expected to relapse at high rates. Approximately 25% of participants without any benefit at 12 months improved meaningfully in the second year. Further, participants with a history of electroconvulsive therapy or transcranial magnetic stimulation benefited greatly with adjunctive VNS compared with sham VNS. Discussion & Conclusions In markedly TRD, adjunctive active VNS was more effective in reducing symptoms and improving function and QoL than a sham intervention administered over 1 year. Continued treatment with active VNS was associated with durable improvement.