The Re-Emerging Role of Therapeutic Neuromodulation
The brain’s activity is able to be adjusted therapeutically through electrical pulses, medicine, or a combination of the two. Focusing on electrical neuromodulation, Rush University Medical Center, Department of Psychiatry Professor Dr. Philip G. Janicak and colleagues discuss the various techniques in which electrical currents are induced within the peripheral or central nervous tissue: electroconvulsive therapy (ECT), vagus nerve stimulation (VNS), transcranial magnetic stimulation (TMS), and deep brain stimulation (DBS). The electrical currents regulate certain dysfunctions within the neural circuits, impacting the brain at certain time installments, moderating the beneficial effects and decreasing the adverse effects.1 These types of therapy are currently being considered for many different psychiatric disorders; however, it is most commonly used for severe cases of treatment-resistant depression.1 Janicak ad colleagues focus on the neuromodulation treatments that are currently FDA-approved for the treatment of depression in their article “The Re-emerging Role of Therapeutic Neuromodulation.”
Electroconvulsive therapy has been used effectively over the past 70 years, and is known as the most effective form of neuromodulation that exists today. According to Janicak and colleagues, with ECT, electrical currents, strong enough to induce seizure, are delivered to the central nervous system, and over the course of six to 12 sessions, severe depression may be resolved.1 However, when antidepressants were introduced in the 1950s, the use of ECT declined and still has yet to recover. Additionally, Janicak and colleagues state that several important factors continue to hinder its popularity, as access and expertise are limited in many parts of the country, the patient’s cognition is temporarily negatively affected, relapse rates are high, the cost of the therapy is high, and the public’s perception of the treatment is often negative.1 In order to improve upon these issues, studies are currently being conducted. For instance, the National Institute of Mental Health has sponsored the Consortium on Research with ECT (CORE) group to research how to effectively maintain the benefits of ECT longer. Also, there are studies being conducted regarding placement of electrodes and wavelength characteristics, looking to increase the benefits and decrease the adverse effects.
In 1997, vagus nerve stimulation was introduced as a treatment for epilepsy; however, in 2005, it became FDA-approved for the treatment of severe, treatment-resistant depression—the first implantable device to gain such approval.1 The vagus nerve itself regulates a person’s heart rate, intestinal motility, and gastric acid secretion, as information is transmitted to specific brain regions which have serotonergic and noradrenergic nerve distribution.1 These same neurotransmitters play an active role in major depression. According to Janicak and colleagues, with VNS , a pulse generator is placed subcutaneously in the patient’s chest, on the upper left side. The generator is attached to wires, which are run up through the patient’s neck to the left vagus nerve. Electrical signals are sent from the generator to the nerve via the wires every few seconds, and the strength of the signals are adjusted using a computer. Common side effects are voice alteration, cough, and shortness of breath; however, they may improve when the intensity of the electrical signals is adjusted.1 In a study conducted to measure the efficiency of VNS in 74 patients with treatment-resistant depression, after three months, 37 percent of patients responded to the treatment, and 17 percent were successfully in remission.4 Results grew, and at the one year mark, 53 percent had responded to the treatment and 33 percent were in remission.4 However, Janicak and colleagues state that as many insurance companies do not reimburse VNS treatment, it is not a frequently used treatment.1
More recently, transcranial magnetic stimulation has been FDA-approved for treatment-resistant depression.1 According to Janicak and colleagues, with TMS, an ferromagnetic coil delivers magnetic pulses caused by electrical charges to the left dorsolateral prefrontal cortex of the brain in fast, repetitive successions.1 Usually, TMS treatment is conducted on an outpatient basis, and a standard treatment course consists of five sessions per week for four to eight weeks.1 The largest trial of TMS treatment was conducted by O’Reardon and colleagues, who specifically studied the difference between active TMS treatment and non-active TMS treatment. They found that patients who received active TMS had better treatment responses than those who did not. In fact, remission rates were 14 percent for those receiving active TMS and six percent for those not receiving active TMS. Also, the treatment was well tolerated, and the most common side effects were headache and pain or discomfort at the application site.
Deep brain stimulation is a neurosurgery in which electrical currents are directed at specific locations within the brain. Both reversible and adjustable, a device is inserted subcutaneously into both the left and right upper chest of the patient.1 Then, electrodes, attached to wires, are run subcutaneously behind the patient’s ears and into burr holes made in the skull, leading to specific locations within the central nervous system.1 Janicak and colleagues state DBS is approved for the treatment of Parkinson’s disease, depression, and severe obsessive-compulsive disorder (OCD).1 Adverse effects of the treatment include: seizure, bleeding, infection, device malfunction, memory disruption, cognitive changes, psychiatric symptoms, and intracranial bleeding.1
According to Janicak and colleagues, cost of treatment must always be included in the patient’s risk-benefit analysis when considering undergoing neuromodulation.1 As many patients do not have insurance coverage, and many insurance providers do not cover neuromodulation treatment, discussing cost is important. Some device manufacturers will offer programs that aid in cost and coverage obtainment.7 However, direct cost is not the only cost the patient should be made aware of, as indirect cost may also significantly impact the patient.1 For instance, inability to work, caretaker and other assistance, and inpatient versus outpatient procedures all should be discussed with the patient before neuromodulation treatment is begun.1
 Janicak, P.G.; Dowd, S.M.; Rado, J.T.; Welch, M.J. (2010). The Re-emerging Role of Therapeutic Neuromodulation. Current Psychiatry 9(11): 66-74.
 Kellner CH, Knapp RG, Petrides G, et al. Continuation electroconvulsive therapy vs pharmacotherapy for relapse prevention in major depression. A multisite study from the Consortium for Research in Electroconvulsive Therapy (CORE). Arch Gen Psychiatry 2006;63:1337-1344.
 Sackeim HA, Prudic J, Nobler MS, et al. Effects of pulse width and electrode placement on the efficacy and cognitive effects of electroconvulsive therapy. Brain Stimulat. 2008;1:71-83.
 O’Reardon JP, Solvason HB, Janicak PG, et al. Efficacy and safety of transcranial magnetic stimulation in the acute treatment of major depression: a multisite randomized controlled trial. Biol Psychiatry. 2007;62:1208-1216.
 Janicak PG, O’Reardon JP, Sampson SM, et al. Transcranial magnetic stimulation in the treatment of major depressive disorder: a comprehensive summary of safety experience from acute exposure, extended exposure, and during reintroduction treatment. J Clin Psychiatry 2008;69:222-232.
 Pilitsis JG, Bakay RAE. Deep brain stimulation for psychiatric disorders. Psychopharm Rev 2007;42(9):67-74.
 Health insurance coverage. NeuroStar TMS Therapy® Web site. Available at http: / /www.neurostartms.com/TMSHealthhisurance/Health-Insurance-Coverage.aspx.