Vagus nerve stimulation shows lasting benefit in treatment-resistant depression

Vagus nerve stimulation shows lasting benefit in treatment-resistant depression

Two-year data show that the addition of VNS to standard care can result in lasting symptoms, function, and quality of life in one of the most difficult-to-treat depression populations.

Study: Durability of benefit from vagus nerve stimulation in markedly treatment-resistant major depression: a RECOVER study report. Photo credit: BigBlueStudio/Shutterstock.com

In a recently published study in theInternational Journal of NeuropsychopharmacologyResearchers characterized function, depressive symptoms, and quality of life (QoL) over two years of vagus nerve stimulation (VNS) in individuals with severe, chronic treatment-resistant depression (TRD).

High resistance to treatment limits the long-term consequences of depression

Most people with major depressive disorder improve after one to three attempts at antidepressant treatment, but this does not happen in 18% to 33% of patients. Individuals with difficult-to-treat depression, or TRD, are more likely to experience hospitalizations, relapses, disabilities, and suicide attempts than those who respond to treatment.

TRD presents two fundamental challenges: achieving and maintaining benefit, particularly in patients with long disease duration and multiple failed treatment attempts.

The likelihood of symptomatic improvement decreases as resistance to therapy increases. Likewise, the likelihood that the benefit will last decreases as treatment resistance increases.

For TRD, assessing the durability of initial benefit is critical to assessing the clinical impact of treatment in patients who are more likely to lose it due to chronic disease and prior nonresponse.

The RECOVER study tracks long-term outcomes during ongoing VNS

In the present study, researchers evaluated clinical outcomes after VNS in individuals with TRD. The first phase of the triple-blind, randomized RECOVER trial evaluated the safety and efficacy of additional VNS therapy for 12 months in patients with TRD and assigned them either additional active or sham VNS therapy along with usual care (TAU).

After the 12-month blinded phase, all participants received open-label active VNS in addition to TAU. The analysis focuses on outcomes during ongoing treatment without a control condition.

The current analysis included participants randomized to active VNS for the first 12 months. Depressive symptom severity was assessed using the clinician-rated and self-reported Quick Inventory of Depressive Symptomatology (QIDS) and the Montgomery, Åsberg Depression Rating Scale (MADRS).

For each scale, a partial response (PR) or a response was defined as ≥30% or ≥50% decrease from baseline, respectively. A score of ≤5 on the QIDS scale and ≤9 on the MADRS scale indicated remission.

For these scales, meaningful benefit (MB) was synonymous with PR and significant benefit (SB) was synonymous with response. The Clinical Global Impression, Improvement (CGI-I) scale was used to assess general psychiatric status, with scores of ≤3, ≤2, and 1 indicating MB, SB, and remission, respectively.

A subset of the QoL Enjoyment and Satisfaction Questionnaire was used to assess quality of life and yielded the minimal clinically important difference (MCID) of an increase of 11.89% from baseline, indicating MB.

The impact of depression on daily activities was assessed using item 6 of the Work Productivity and Activity Impairment Questionnaire, with MB defined as a reduction of two or more points.

All measurements were combined into a single, composite metric with a value of 0.3 based on the number of domains containing one MB. A composite score of 0 indicated no significant benefit (NB), 1 indicated an MB, and 2 or 3 indicated SB. Rates of each outcome measure were determined at 12, 18, and 24 months after randomization.

Durability of benefit was estimated as the proportion of participants with ≥MB at 12 months who at least maintained that status at 18 and 24 months. In contrast, the proportion of participants with MB or SB at 12 months but NB at later time points reflected loss of benefit. Furthermore, the proportion of participants with SB at 12 months but NB at later time points suggested relapse. Benefit was also assessed in patients with NB at 12 months.

In most patients, the significant benefit was maintained over two years

214 participants with an average age of 55.2 years took part in the study. Most participants were female (68%) and unemployed (72%). The study population spent 52.6% of their lives with a depressive illness, had failed multiple previous antidepressant and interventional treatments, had a very poor quality of life, and was functionally impaired.

At 12 months, 80% of the sample achieved at least MB on the three-item composite measure. At 18 and 24 months, 83.6% and 82.4% of the sample achieved at least MB, respectively.

Of participants who were in remission at 12 months, approximately 59% to 66% maintained remission at 18 months, and approximately 48% to 70% maintained remission at 24 months. Across all outcome measures, approximately 17% of participants experienced loss of benefit at 18 months and 19% at 24 months.

The relapse rate was 6.7% at 18 months and 7.8% at 24 months. In addition, many participants with NB achieved at least MB at later time points at 12 months, with approximately a third achieving improvement at 18 months and nearly 38% at 24 months.

VNS shows durable benefit in highly treatment-resistant depression

Taken together, a significant proportion of individuals with TRD treated with TAU and VNS achieved benefit on symptom, functional and quality of life measures at 12 months. Approximately 80% of participants who achieved at least MB at 12 months maintained at least MB in the following 12 months while continuing additional VNS.

A subset of participants (approximately 38%) who had not achieved MB at 12 months had achieved this status at 24 months. Rates of performance loss were low and relapses were rare.

The authors note that sustained and emerging benefits were not explained by changes in concomitant medications or exposure to other interventional treatments, supporting the durability of VNS-associated outcomes in a population with exceptionally high treatment resistance and disease chronicity.

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