The device manufacturer swears it’s effective. The FDA approved it. But is there any evidence for vagus nerve stimulation (VNS) for treatment-resistant depression?
Susan Ricketts contacted me after reading “Vagus nerve stimulation (VNS) for depression: Does it work?” on this site. Now, in an exclusive interview, Ricketts describes her experience as Project Coordinator on the D-02 clinical trial of VNS for depression. It was the single randomized, controlled trial submitted to the FDA, but one Ricketts says was so poorly managed she ended up walking away from the job, minus a paycheck, but with integrity intact.
Excerpts from the interview begin in Part 2 of this article; first, some background information:
What is vagus nerve stimulation?
In VNS, a device is surgically implanted in the patient’s neck and connected to the vagus nerve. When switched on, the device shoots electrical impulses through that nerve and into the brain.
VNS has been shown to be effective in controlling seizures in severe cases of epilepsy, but there has never been solid evidence it works on depression.
Even so, it was approved by the FDA for treatment-resistant depression in 2005, over loud objections from FDA staff and the consumer group Public Citizen, among others. The approval process raised so many red flags it was the subject of a U.S. Senate investigation.
Many people think VNS is a radical but effective last-ditch treatment for depression that responds to nothing else. That belief is due largely to long-term and continuing marketing efforts by Cyberonics, Inc., the device manufacturer.
Cyberonics has managed to get its own press releases and a few vaguely scientific studies onto high-profile health websites. Unfortunately, that’s where many people go for health information, not realizing these sites are often used as free advertising space by pharmaceutical and device manufacturers with a serious financial stake in moving product off the shelves.
Understanding scientific studies
To understand why the evidence falls short, it’s important to know a few buzzwords.
In a randomized, controlled clinical trial, scientists compare the effects of a treatment on two randomly populated groups of patients, one group receiving the treatment being tested and the other group, called a control group, not getting the treatment. The control group receives a placebo or “sugar pill” (in the case of VNS, an inactive device), because patients who know whether they are being treated or not might be subject to the “placebo effect” and show improvement (or not) due to their own expectations.
Researchers try to eliminate every possible variable that could influence the results other than the treatment itself.
To envision this, imagine you are trying to find out if orange popsicles melt faster than green popsicles. You lay the popsicles out in two groups and observe them, and note that the orange popsicles do, in fact, melt much faster than green ones. Then you realize the group of orange popsicles was in direct sunlight. Oops! That’s an example of a variable affecting your results. Good thing you didn’t rush an article to the scientific journals.
Most VNS trials for depression were decidedly of the hot-popsicle type. In one study, for instance, subjects were allowed to use treatments other than VNS during the study, and to switch between the additional treatments. Even if the results of such a trial showed depression was relieved, it would be impossible to tell whether it was due to VNS, the add-on treatment, the combination – or pure chance.
Behind the scenes
Four years after VNS’s approval for depression, a report to Oregon Health & Science University’s Center for Evidence Based Policy found only one randomized, controlled study in the literature, and that study showed no benefit for VNS.
As it happens, that single trial, the D-02 study, was the one Susan Ricketts worked on. What she saw shocked her.
See Part 2