Deep brain stimulation (DBS), used in treating Parkinson disease and other movement disorders, has emerged as a promising approach for early Alzheimer disease and for treatment-resistant depression (TRD), according to recent journal articles and key researchers in the neuromodulation field.
The evolution of DBS for various neuropsychiatric disorders results from advances in structural and functional brain imaging, increased understand-ing of neurocircuitry of the brain, and improvements in neurosurgical techniques and equipment, explained Helen Mayberg, MD, Dorothy C. Fuqua Chair of Psychiatric Neuroimaging and Therapeutics at Emory University School of Medicine, who conducts depression-related DBS research.
As early as 1997, the FDA approved DBS for treatment of essential tremor; this was followed in 2002 by approval for use in advanced Parkinson disease and, in 2003, for dystonia. To date, more than 85,000 patients worldwide have had DBS devices implanted.
In a recent editorial, Andres Lozano, MD, PhD,1 RR Tasker Chair in Functional Neurosurgery at the University Health Network (UHN) in Toronto, wrote that beyond DBS’s “striking clinical benefits” for movement disorders, it may have potential for patients with non-motor neurological and psychiatric disorders.
In 2009, the FDA approved a humanitarian device exemption for DBS therapy (Medtronics’ Reclaim) to suppress the symptoms associated with chronic, severe obsessive-compulsive disorder, said Mayberg.
Possible FDA consideration of DBS for Alzheimer disease and for TRD must await the results of stimulation versus sham trials, said Peter Giacobbe, MD, Assistant Professor at the University of Toronto and Staff Psychiatrist at UHN, where he serves as Head of the ECT service. He also programs DBS devices and provides preoperative and postoperative psychiatric management of patients receiving DBS.
According to a search of open studies listed on www.clinicaltrials.gov and a review article, DBS also is being studied for bipolar disorder, PTSD following combat, obesity, anorexia, addiction, Tourette syn-drome, and epilepsy, among other disorders.2 Despite the growing interest in DBS, Hariz and Hariz3 recently warned against the testing and touting of DBS for “dubious indications,” such as enhancing normal cognition and treating antisocial behavior.
The DBS procedure
The DBS procedure involves implanting electrodes within specific brain circuits to modulate the circuits’ activity, either to suppress pathological neuronal activity or to drive underactive output, according to Lozano.
“Electrodes are commonly placed with patients fully awake, which allows the surgeon to pinpoint the precise location in the brain using microelectrode recordings of neurons at the target,” he wrote in the editorial. “The surgeon can also gauge the patient’s response to stimulation, which helps guide the final placement of the electrodes. The electrodes are then connected to an implanted pulse generation (along the lines of a standard cardiac pacemaker), which can be programmed to deliver continuous stimulation for several years—batteries last 4 to 5 years or longer with recharging.”
1. Lozano AM. Deep brain stimulation therapy. BMJ. 2012;344:e1100.
2. Lyons MK. Deep brain stimulation: current and future clinical applications. Mayo Clin Proc. 2011;86:662-672.
3. Hariz MI, Hariz GM. Hyping deep brain stimulation in psychiatry could lead to its demise. BMJ. 2012;345:e5447.
4. Hamani C, McAndrews MP, Cohn M, et al. Memory enhancement induced by hypothalamic/fornix deep brain stimulation. Ann Neurol. 2008;63:119-123.
5. Laxton AW, Tang-Wai DF, McAndrews MP, et al. A phase I trial of deep brain stimulation of memory circuits in Alzheimer’s disease. Ann Neurol. 2010;68:521-534.
6. Laxton AW, Lozano AM. Deep brain stimulation for the treatment of Alzheimer disease and dementias. World Neurosurg. 2012 Jun 19; [Epub ahead of print].
7. Smith GS, Laxton AW, Tang-Wai DF, et al. Increased cerebral metabolism after 1 year of deep brain stimulation in Alzheimer disease. Arch Neurol. 2012;69:1141-1148.
8. Mayberg HS, Lozano AM, Voon V, et al. Deep brain stimulation for treatment-resistant depression. Neuron. 2005;45:651-660.
10. Kennedy SH, Giacobbe P, Rizvi SJ, et al. Deep brain stimulation for treatment-resistant depression: follow-up after 3 to 6 years. Am J Psychiatry. 2011;168:502-510.
11. Lozano AM, Giacobbe P, Hamani C, et al. A multicenter pilot study of subcallosal cingulate area deep brain stimulation for treatment-resistant depression. J Neurosurg. 2012;116:315-322.
12. Holtzheimer PE, Kelley ME, Gross RE, et al. Subcallosal cingulate deep brain stimulation for treatment-resistant unipolar and bipolar depression. Arch Gen Psychiatry. 2012;69:150-158.