All of us—researchers, journalists, patients and their loved ones--are desperate for genuine progress in treatments for severe mental illness. But if the history of such treatments teaches us anything, it is that we must view claims of dramatic progress with skepticism, or we will fall prey to false hopes.
Case in point: a depression treatment, pioneered by neurologist Helen Mayberg of Emory University, that involves electrically stimulating the brain with electrodes inserted through holes drilled in the skull. In 2005, Mayberg and colleagues reported that stimulating a region called Brodmann area 25 can relieve severe, intractable depression in two out of three patients.
Since then, many journalists and scientists have lauded Mayberg's research. In 2005, National Public Radio called her treatment "revolutionary." In 2006, the journalist David Dobbs, in a glowing profile of Mayberg in The New York Times Magazine, said her "incredible" results were "already changing how neuroscientists and psychiatrists think about depression."
More recently, her linkage of depression to area 25 has been praised by heavyweights such as Nobel laureate and neuroscientist Eric Kandel of Columbia and Thomas Insel, director of the National Institute of Mental Health. Last October, James Gorman of The New York Times cited Mayberg's research in a report on how the Pentagon plans to "spend more than $70 million over five years to jump to the next level of brain implants."
Mayberg continues to report promising results, most recently at a lecture that I attended yesterday at New York University. The most powerful part of her presentation consisted of depressed patients describing how their mood lifted after implants stimulated their brains.
But Mayberg "buried the lead," as we journalists like to say. Midway through her talk, she mentioned that a multi-center, controlled trial of her method of deep-brain stimulation has halted.
Mayberg, who did not participate in the trial, did not know why exactly it had stopped. But she suspected that either subjects receiving stimulation of area 25 did worse than expected, or controls receiving "sham" surgery did better than expected, or both. Mayberg later told me by email that the so-called BROADEN (BROdmann Area 25 DEep brain Neuromodulation) trial was was overseen by St. Jude Medical Inc., for which she consults.
According to Neurotech Business Reports, an industry newsletter, the FDA suspended the BROADEN trial last fall because it failed a "futility analysis," which considers whether an experimental treatment has a reasonable chance of improving upon current treatments. (See this post by the terrific blogger "Neurocritic" for more on the suspended trial.)
I've always had doubts about Mayberg's claims. Her implant experiments have involved small numbers of patients (six in her 2005 study and 17 in a 2012 trial). I'm also troubled by Mayberg's links to medical-device manufacturers, such as St. Jude. Mayberg's potential conflicts of interest have been explored by one of her rare critics, journalist Alison Bass.
Moreover, I've delved into the history of deep-brain stimulation, so I know that it has inspired unfulfilled hopes in the past. (See my 2005 Scientific American article on brain-implant pioneer Jose Delgado.) Although the technology has become more refined, deep brain stimulation is still "associated with surgical risks (e.g., hemorrhage) and psychiatric complications (suicidal attenuation, hypomania) as well as high costs," according to a recent review in Nature.
In a post last September, I expressed doubts about Mayberg's work and criticized the reporting on her by David Dobbs. In a comment on my post, Dobbs vigorously defended Mayberg and himself, accusing me of desiring not "to inform, answer, or illuminate, but to deceive, darken, and distract." (See his entire comment following my blog post.)
My guess is that Dobbs, in spite of the suspended BROADEN trial, will double down on his support of Mayberg's approach to depression. At NYU, Mayberg admitted that she has to wonder why her implant studies show better results than the BROADEN trial apparently did. "Do my patients want to please me?" she asked.
She nonetheless remained upbeat. She told me by email: "The field will hopefully continue to move forward independently as it is doing, and hopefully companies will see the value of pursuing this approach given the research results."
The question is, at what point does hope do more harm than good?
For more information: Last September, Financial Times gave an upbeat overview of clinical research on DBS, including the recently suspended BROADEN trial, which according to the newspaper had 200 patients. Psychiatrist Carl Erik Fisher discussed the risks and benefits of deep brain stimulation for mental illness in December in Scientific American Mind. Mayberg's research was praised by physician Sanjay Gupta on CNN in 2012 and by journalist Andrew Solomon on National Public Radio this month. So far, no prominent journalist has mentioned the suspension of the BROADEN trial.