The Question of When
In the 17 years that we have published this newsletter, one of the greatest therapeutic successes we have witnessed has been deep brain stimulation. The therapy has helped hundreds of thousands of patients with a variety of neurological disorders and much progress has been made in device design and implantation. Still, one major unresolved issue about DBS concerns timing. How soon in the progression of a disease or disorder should a patient begin a DBS regimen? And once begun, how long should the therapy continue before ceasing stimulation or explanting in the event of lack of response?
Traditionally, DBS, like most implanted neuromodulation therapies, is only begun once a patient has failed to respond to available pharmaceutical therapies, or in the case of Parkinson’s disease, after a drug like L-dopa shows diminished effectiveness. Some clinicians have argued that waiting too long to begin a DBS regimen could limit its therapeutic value and that neuromodulation begun at an earlier stage of disease progression could have a curative effect.
We were thus encouraged by a Vanderbilt University study, published this month in Neurology, that shows DBS may slow the progression of tremor for early-stage PD patients. Patients were randomized to receive DBS plus drug therapy or drug therapy alone; the drug therapy alone group was seven times more likely to develop new rest tremor after two years in comparison to the DBS plus drug therapy group.
We were also encouraged by the release of second-year data from the ADvance trial of DBS-fornix for treatment of Alzheimer’s disease. Writing in the Journal of Alzheimer’s Disease, the authors from the University of Toronto reported that patients over 65 that benefited from DBS-f in the first 12 months of the trial continued to benefit in the second year. Data released by Abbott last year from the Broaden trial of DBS for depression showed that response to the therapy improved after the initial six months.
While clinical trials of pharmaceutical therapies often have a six-month time horizon, it should be clear to regulators that device interventions should be encouraged to explore at least a 12- to 24-month window. LivaNova (formerly Cyberonics) has reported a similar long-term improvement in response to its VNS depression therapy, a finding that helped motivate the company to encourage CMS to reconsider its National Coverage Determination.
The timing of when to commence and cease a DBS therapeutic regimen can have a dramatic effect on patient outcome. Regulators should allow clinicians and investigators as much latitude as possible to treat patients at any stage of disease progression.
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