Those aren’t stellar scientific results for a device as invasive, risky and expensive ($20,000) as VNS, and many researchers criticize the FDA approval based on what they consider paltry evidence. But Husain sees even these relatively modest numbers of positive outcomes as significant and meaningful to patients who have failed to benefit from other treatments and tend to be in desperate straits. Moreover, Husain says, patients seem to benefit the longer the VNS device is in place, and even those whose symptoms don’t improve significantly may be able to go longer between ECT sessions.
Repetitive transcranial magnetic stimulation has been approved in Canada for treatment-resistant depression and, although not yet cleared for that purpose in the United States, it is offered “off label,” much as some drugs are prescribed for conditions other than those for which the medications are FDA-approved. Like ECT, rTMS works from outside the skull, but rather than shocking the brain with a surge of externally generated electricity, it creates a focused magnetic field that induces a current inside the dorsolateral prefrontal cortex, at the front of the skull, where brain-imaging studies of some depressed patients have shown abnormal activity patterns. But the neuroscience isn’t yet clear about which depressive symptoms these abnormal activities may produce—or whether stimulating the brain region with rTMS increases beneficial activity, promoting optimism and motivation, or inhibits negative brain activity, reducing anxiety and agitation.
Yet, while there is much to be learned about how rTMS works, some patients seem to be benefiting. J.T. of Arlington, Mass., sidelined by depression throughout his twenties, has been receiving rTMS for three years at a clinic run by Alvaro Pascual-Leone, director of the Center for Non-Invasive Brain Stimulation at Boston’s Beth Israel Deaconess Medical Center. J.T. describes his treatment sessions as “routine as getting a haircut.” He reads a magazine while a technician circles a wand containing a stimulation coil over the left side of his forehead. For half an hour, with brief pauses, the device fires magnetic pulses at a rate of 20 times per second into J.T.’s left dorsolateral prefrontal cortex. Researchers think this bombardment gradually affects the brain activity there, perhaps restoring the proper balance of neurotransmitters.
J.T. says he knew the treatments were beginning to help when the musical score of his life changed from the dark strains of Metallica to a Mozart symphony. At first, J.T. received treatment several times a week, which tapered off to once a month. But then symptoms returned, and he is now on a biweekly schedule.
Some critics contend that because rTMS penetrates
only a few centimeters into the cortex, it’s unlikely to have much effect
on the brain circuitry or chemistry implicated in depression. (Pascual-Leone
counters that although the effect is directly exerted in part of the cortex,
it spreads through this “window” to deeper parts of the brain along specific
connections.) They note that in a double-blind trial of the treatment,
only one in three patients appeared to benefit—not a clinically significant
improvement, in some views. But the success rate approaches that for VNS
and is not much worse than the roughly 40% achieved by ECT administered
at community hospitals. (At academic medical centers, four out of five
ECT treatments succeed, presumably because physicians there are better
trained and more experienced.)
Deep brain stimulation (DBS), approved for severe cases of Parkinson’s disease but used on only a relative handful of patients in research studies of depression, uses electrodes implanted directly into the brain in a region that has been implicated in depression. The electrodes are connected to a pacemaker-like device in the chest or neck that can be controlled externally, as in VNS.
DBS is being explored as a reversible alternative to brain surgery, the last, desperate recourse for severely depressed patients who have exhausted all conventional alternatives. When used to treat depression and Parkinson’s disease, DBS can have an effect described as astonishing and immediate, as if there were switches in the brain waiting to be thrown.
There may be no single switch for depression, but several groups of researchers using DBS for obsessive-compulsive patients have noted that stimulating the anterior limb of the internal capsule improved patients’ moods, lessened their anxiety and boosted their motivation. That made sense because neurosurgeons frequently target that portion of the brain, part of a fan-shaped structure in front of the ears that mediates communication between the thalamus, the main relay nucleus in the brain, and parts of the frontal lobes involved in emotion.
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