Around one in five adults suffers from severe depression at some point in their lives. Many people experience an improvement after a few attempts at treatment, but for up to a third of patients, conventional antidepressants or psychotherapy do not provide sufficient relief. This condition, known as treatment-resistant depression, can last for years or even decades. New research now suggests that a small implanted device could provide significant and lasting improvement for people with the most severe forms of the condition.
Severe Depression Has a Massive Impact on Quality of Life
Severe depression is characterized by persistent, profound depression that can last for weeks or months and affects a person’s entire way of thinking, feeling and acting. Those affected often feel a pronounced hopelessness, inner emptiness or numbness and almost completely lose interest in things that used to be important or enjoyable to them. Joy, motivation and drive are missing, even simple everyday tasks such as getting out of bed, showering or shopping can seem almost impossible to accomplish. Mentally, there is often a lot of brooding, negative thought spirals and a very pessimistic view of oneself, the environment and the future. Many sufferers feel worthless, reproach themselves excessively or experience strong feelings of guilt. Concentration and the ability to make decisions are significantly impaired. In severe cases, recurring thoughts of death or suicide occur, which is a serious warning situation.
Severe depression also manifests itself physically. There is often pronounced exhaustion, sleep disturbances, changes in appetite and weight as well as physical complaints such as headaches, back pain or stomach pain without a clear organic cause. Some people appear very slow in movement and speech, others experience agonizing inner restlessness. Those affected usually withdraw socially, avoid contact and neglect work, school or family commitments.
How Vagus Nerve Stimulation Works
Scientists at Washington University School of Medicine in St. Louis conducted a large, multi-center clinical trial. They found that a vagus nerve stimulation device was associated with sustained improvement in depressive symptoms, daily functioning and overall quality of life. For most patients who showed improvement after one year, these improvements lasted for at least two years. The participants in the study had been living with depression for an average of 29 years and had already tried around 13 treatments without success. These included intensive options such as electroconvulsive therapy and transcranial magnetic stimulation, illustrating how difficult their condition was to treat. The latest results come from the ongoing RECOVER study and have been published in the International Journal of Neuropsychopharmacology.
“We believe the sample in this study represents the sickest treatment-resistant depressed patients ever examined in a clinical trial,” said lead author Charles Conway, MD, professor of psychiatry and director of the WashU Medicine Treatment Resistant Mood Disorders Center. “There is an urgent need to find effective treatments for these patients, who often have no other options. With this type of chronic, disabling disorder, even a partial response to treatment can be life-changing, and with vagus nerve stimulation, we’re seeing that the benefits are long-lasting.”
The RECOVER trial was designed to test whether the addition of vagus nerve stimulation (VNS) to ongoing treatment can improve outcomes for people with treatment-resistant depression. The therapy involves surgically implanting a device under the skin in the chest area. The device sends carefully controlled electrical signals to the left vagus nerve – an important communication pathway between the brain and many internal organs.
The VNS Therapy System is manufactured by LivaNova USA, Inc., which sponsored and funded the RECOVER study. The study collects long-term data on mood, daily functioning and quality of life of people with severe treatment-resistant depression. One goal of the research is to help the U.S. Centers for Medicare and Medicaid Services (CMS) decide whether to expand coverage for the therapy.
Insight Into the RECOVER Study
Nearly 500 patients were enrolled in the study at 84 sites across the United States. About three-quarters of the participants were so severely affected by depression that they were unable to work. All patients received the implanted device, but only half had the device activated in the first year to allow for comparison. The researchers tracked changes in depression severity, quality of life and daily functioning. A response was considered significant if symptoms improved by at least 30% compared to the start of the study. A reduction of 50% or more was classified as a “substantial” response.
Conway emphasized that even minor improvements can dramatically change a person’s life. Major depression can leave people feeling “paralyzed by life,” unable to perform basic daily activities, and at a higher risk of hospitalization or early death. Previous results from the blinded first year of the study showed that patients with activated devices spent more time with improved mood, better functioning and higher quality of life than those whose devices were not active. However, the primary measurement tool (the Montgomery-Åsberg Depression Scale, which measures the severity of depressive episodes) showed no statistically significant difference between the two groups.
Long-Lasting Benefits
In the latest analysis, the researchers focused on patients whose devices were active from the start of the study. They wanted to find out whether the improvements seen after 12 months were still sustained after 24 months. They also investigated whether some patients who did not improve in the first year might later respond to continued treatment. Of the 214 patients who were actively treated from the start, around 69% (147 people) showed a significant response in at least one measurement after one year. Of the patients who showed a benefit at 12 months, more than 80% maintained or improved their outcomes at two years in terms of depression, quality of life and daily functioning. For patients with a significant response after one year – defined as at least a 50% reduction in symptoms – 92% were still benefiting after two years.
Almost a third of participants who had not improved after the first year reported positive effects at the end of the second year, suggesting that the therapy may take longer to work for some people. Relapse rates remained low among those who had responded to the therapy, particularly among those who had responded most strongly. The researchers also found that more than 20% of treated patients, or 39 people, achieved remission after 24 months. This means that their symptoms had subsided to such an extent that they were able to resume their daily lives as normal – a result that Conway described as particularly remarkable. The researchers were shocked that one in five patients had virtually no depressive symptoms after two years. Given such results in this complicated disease, they are optimistic about the future of this treatment. These results are highly atypical, as most studies on markedly treatment-resistant depression show very little sustainability of effect, certainly not over two years.