Psychiatry and the surgical treatment of depression, Part II
Yesterday I posted on a NY Times article about an implantable vagus nerve stimulator being used to treat severe depression. This device is surgically implanted in the chest and electrical leads are threaded up into the neck in contact with the vagus nerve. It was developed by Cyberonics originally for the purpose of treating intractible epilepsy and the company is seeking FDA approval to expand its indications.
The previous post expressed my "squeamishness" with this kind of surgical solution for modifying mood and behavior. In the end however, I recognized both the paralyzing impact of severe depression and the need to accept any therapy that is proven to work where other less invasive therapies have not.
I closed with an admonition that "when we're dealing with those aspects of our being that cut at the very heart of our humanity, we need to be especially careful."
Unfortunately, regarding this device, it appears that such has not been the case.
In June 2004, an FDA advisory committee recommended such approval. However, the following August the FDA denied approval pending further data from the company. (Advisory committee recommendations are not binding and can be overruled by the agency.) Recently, the FDA announced that it is reconsidering approval for the marketing of this device for the treatment of intractable depression.
In a randomized trial, the vagus nerve stimulator was implanted in 235 severely depressed patients. In only half of them, was it turned on. 17 of 111 such patients reported significant improvement. 11 of 110 in the control group did. (No mention was made of the remaining 24 patients.) The difference was not statistically significant which means that it could have been attributed to mere chance. In other words, efficacy was not demonstrated by this study.
In addition, this device is not without side-effects. Patients have complained of hoarseness and "odd" inflections in the voice. At least one patient cited a constricting pain in the back of her throat which at times left her unable to speak. In addition, removal is technically difficult should this ever be necessary and the wire leads must generally be left in place. It should also be noted that there are only two years of safety data thus far which is not much for a device that presumably will be left in for life.
So why did the advisory committee approve this device? With no phase III trials demonstrating efficacy and no long term safety data on depressed patients, their decision amazes me. This hardly seems the appropriate background for a "reasonable assurance" of safety and efficacy as mandated by the FDA. As it turns out, this recommendation appears to have arisen largely out of emotion.
The committee's chairperson, neurologist Kyra Becker MD made the extraordinary statement that if she had voted her conscience, soley on the basis of the evidence, she would have voted not to approve.
Huh?
Then on what basis did she vote? I've heard some poorly thought out statements to the media before, but this one redefines the term malapropism. She also relates that "the whole meeting was uncomfortable, and everyone wanted to see another trial done, no question about it." So why vote for approval before such a trial was done?
Dissenting committee member Dr. Richard Malone said "I walked out of there thinking I was nuts. It was stunning..."
Since there are so few options remaining for patients with intractable depression, grasping at straws can seem the compassionate thing to do. Unfortunately, such decisions can have unintended consequences.
First, severe depression almost always has other treatments that are efficacious, usually in the form of multi-drug regimens. This being the case, treatments with unproven efficacy might very well direct a patient away from other potentially beneficial therapies. In fact, with FDA approval, there is nothing to stop physicians enamored by high tech solutions from utilizing this device in patients with even moderate depression (or severe depression for which established therapies haven't been exhausted.)
Second, any treatment such as this device that may be capable of making depression better, may in fact make it worse. What would we think if down the line, we found higher rates of social dysfunction or suicide among those who opted for this product? Every intervention has potential downsides.
Third, should a device with essentially no established benefit be allowed to be aggressively marketed by the company? This is exactly the right that FDA approval would grant. Should insurance companies and other third-party payers be required to foot the bill for this $15,000 treatment (not including the costs of implantation and maintenance)?
For these reasons, the FDA needs to make a well thought out, rational decision, not one based on emotion as has apparently been done by members of this committee (especially the chairperson).
I agree that there are many bureaucratic obstacles to FDA approval of medical technology, many of which are manifestly unnecessary. Demanding proof of safety and efficacy is not one of them.
As an aside, I will mention that there are some questions about the propriety of the FDA's reconsidering approval in this case:
The previous post expressed my "squeamishness" with this kind of surgical solution for modifying mood and behavior. In the end however, I recognized both the paralyzing impact of severe depression and the need to accept any therapy that is proven to work where other less invasive therapies have not.
I closed with an admonition that "when we're dealing with those aspects of our being that cut at the very heart of our humanity, we need to be especially careful."
Unfortunately, regarding this device, it appears that such has not been the case.
In June 2004, an FDA advisory committee recommended such approval. However, the following August the FDA denied approval pending further data from the company. (Advisory committee recommendations are not binding and can be overruled by the agency.) Recently, the FDA announced that it is reconsidering approval for the marketing of this device for the treatment of intractable depression.
In a randomized trial, the vagus nerve stimulator was implanted in 235 severely depressed patients. In only half of them, was it turned on. 17 of 111 such patients reported significant improvement. 11 of 110 in the control group did. (No mention was made of the remaining 24 patients.) The difference was not statistically significant which means that it could have been attributed to mere chance. In other words, efficacy was not demonstrated by this study.
In addition, this device is not without side-effects. Patients have complained of hoarseness and "odd" inflections in the voice. At least one patient cited a constricting pain in the back of her throat which at times left her unable to speak. In addition, removal is technically difficult should this ever be necessary and the wire leads must generally be left in place. It should also be noted that there are only two years of safety data thus far which is not much for a device that presumably will be left in for life.
So why did the advisory committee approve this device? With no phase III trials demonstrating efficacy and no long term safety data on depressed patients, their decision amazes me. This hardly seems the appropriate background for a "reasonable assurance" of safety and efficacy as mandated by the FDA. As it turns out, this recommendation appears to have arisen largely out of emotion.
The committee's chairperson, neurologist Kyra Becker MD made the extraordinary statement that if she had voted her conscience, soley on the basis of the evidence, she would have voted not to approve.
Huh?
Then on what basis did she vote? I've heard some poorly thought out statements to the media before, but this one redefines the term malapropism. She also relates that "the whole meeting was uncomfortable, and everyone wanted to see another trial done, no question about it." So why vote for approval before such a trial was done?
Dissenting committee member Dr. Richard Malone said "I walked out of there thinking I was nuts. It was stunning..."
Since there are so few options remaining for patients with intractable depression, grasping at straws can seem the compassionate thing to do. Unfortunately, such decisions can have unintended consequences.
First, severe depression almost always has other treatments that are efficacious, usually in the form of multi-drug regimens. This being the case, treatments with unproven efficacy might very well direct a patient away from other potentially beneficial therapies. In fact, with FDA approval, there is nothing to stop physicians enamored by high tech solutions from utilizing this device in patients with even moderate depression (or severe depression for which established therapies haven't been exhausted.)
Second, any treatment such as this device that may be capable of making depression better, may in fact make it worse. What would we think if down the line, we found higher rates of social dysfunction or suicide among those who opted for this product? Every intervention has potential downsides.
Third, should a device with essentially no established benefit be allowed to be aggressively marketed by the company? This is exactly the right that FDA approval would grant. Should insurance companies and other third-party payers be required to foot the bill for this $15,000 treatment (not including the costs of implantation and maintenance)?
For these reasons, the FDA needs to make a well thought out, rational decision, not one based on emotion as has apparently been done by members of this committee (especially the chairperson).
I agree that there are many bureaucratic obstacles to FDA approval of medical technology, many of which are manifestly unnecessary. Demanding proof of safety and efficacy is not one of them.
As an aside, I will mention that there are some questions about the propriety of the FDA's reconsidering approval in this case:
"Cummins (Cyberonics Chief Executive Robert Cummins), who personally owns 1.15 million Cyberonics shares, acknowledged the company appealed to a number of Republican and Democratic Senators and Congressmen, as well as the Senate Finance Committee for help after the negative decision from the FDA."I'll leave it up to the reader to ponder the morality of doing an "end run" around the FDA.
Labels: Ethics, FDA, Junk Science, Medical Technology, Politics, Public Health
posted by The Medicine Man at 5:33 AM
6 Comments:
Whatever the side effects, they are much better than cancer causing drug cocktails that Drs so easily prescribe. You are probably a paid operative of the drug companies.
Anonymous,
See my post today regarding all financial disclosures.
John
My mother was severely depressed all the years we were growing up. I carried on the tradition, feeling chronically, clinically depressed and seeking a cure for my depression for over twenty-five years. I was, oddly enough, one of the “lucky” ones: my depression was partner to an equally common disorder called Attention Deficit Disorder. So though I was at first treated only for the cure for depression alone, with Prozac, which saved me from offing myself but added a hundred pounds to my already hefty frame, I was eventually (in my early forties) treated for ADD with medication that took away the depression for the most part. Some days I can hear it coming, can feel in my gut the angst churning and brewing, but can embrace it for what it is, climb in bed with books and toys and whatever other comfort items I choose, and ride that bitch of a malady out. For it does pass. And as to a “cure” for depression, I still say really good drugs help.
Muna wa Wanjiru has been researching and reporting on Health for years. If You Have Any Comments Or Views That You Would Wish To Share With Our Readers on Cure for Depression, Post Them On His Blog HERE CURE FOR DEPRESSION
I MUST find an alternate "cure" for my intractible depression. I believe I have had these symptoms since birth. I am a 53 yr. old woman in excellent physical health overall, excluding high blood pressure and hypothyroidism, both of which are controlled with medication. During the previous 20 yrs. I've been diagnosed with bipolar I and II disorder with very rapid cycling and frequent mixed state, ADD, dysthemia, borderline personality disorder, major depressive episode, and unipolar depression. I have been hospitalized for suicidal intentions or actual tries at more than 6 hospitals in three states. I have taken nearly every medication available for manic-depression, depression and anxiety. I have been an extremely compliant patient with over a dozen psychiatrists. I have undergone extensive CBT, Dialectic Behavior Therapy, and eclectic modalities of psychotherapy with over a dozen psychologists and LCSW's. I am chronicly suicidal, unable to adequately care for myself including bathing regularly, eating appropriately, and get no exercise. I am highly intelligent and educated including some post grad courses at Harvard just four years ago. I will get relief by suicide within the next 12 to 24 mos. if I cannot get relief from my depression in any other way. I hate to have to do that because I have three grown children who would obviously be traumatized by my suicide. However, my body will begin to go the way of my mind due to lack of care, and rather than such a long and insufferable path to death, I will end it sooner if necessary.
Anonymous,
I hope you get the help you need soon (and that you obviously know you need).
You absolutely have to get to a mental health professional.
John
I was wondering if you are doing any more studies on severe depression and if you need any more volunteers. Only problem being that I cannot eat fish oil because I am a vegan.
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