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Interest Surging in Electroconvulsive and Other Brain Stimulation Therapies

Interest Surging in Electroconvulsive and Other Brain Stimulation Therapies San Diego—A course of electroconvulsive therapy (ECT) every 9 or 10 months keeps her cyclic depression at bay, Kitty Dukakis said in an invited lecture at the annual meeting of the American Psychiatric Association (APA) here in May. Dukakis, the wife of former Massachusetts governor and 1988 Democratic presidential nominee Michael Dukakis, hopes her candor will help counter inaccurate and harrowing portrayals of ECT, such as those in the 1975 film One Flew Over the Cuckoo's Nest, based on Ken Kesey's 1962 novel. Although studies have demonstrated that electroconvulsive therapy (ECT) is an effective and safe treatment for severe major depression, inaccurate perceptions of ECT contribute to lingering stigma and fear regarding its use. (Photo credit: Will McIntyre/www.sciencesource.com) “Patients who are not helped by antidepressant medications and psychotherapy should not have to suffer for months, and in some cases, years, without ECT being an option,” noted Dukakis, who said she first received ECT in 2001, after experiencing deepening “bouts of despair” over 2 decades. Now 70 years old, she details her depression and its treatment, along with her earlier dependence on alcohol and amphetamine diet pills, in Shock: The Healing Power of Electroconvulsive Therapy (New York, NY: Avery; 2006), written with medical journalist Larry Tye. Dukakis' willingness to speak out has helped boost public and physician awareness of ECT's safety and efficacy, said Max Fink, MD, professor emeritus of psychiatry and neurology at the Stony Brook University School of Medicine, Stony Brook, NY. Results from 2 recent multisite collaborative studies also are prompting increased use of ECT worldwide, Fink noted. Remissions occurred with ECT in 86% of 394 patients with major depressive disorder completing the Consortium for Research in ECT study (Kellner CH et al. Arch Gen Psychiatry. 2006;63[12]:1337-1344) and in 55% of 290 patients completing a multisite study led by researchers at the New York State Psychiatric Institute and Columbia University College of Physicians and Surgeons, in New York City (Sackeim HA et al. JAMA. 2001;285[10]:1299-1307). These rates compare favorably with those obtained from use of antidepressant medications in similar patients. In the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial—the first study to examine the effectiveness of medication and other treatment for patients who did not become symptom-free after initial medication—about 30% of patients initially treated with citalopram experienced a remission. Among 727 patients whose symptoms did not remit with citalopram or who could not tolerate it, remission occurred in about 1 in 4 patients given either bupropion, sertraline, or venlafaxine. Thus, STAR*D patients had about a 55% chance of achieving remission with their first or second course of medication (Rush AJ et al. N Engl J Med. 2006;354[12]:1231-1242). However, among 235 patients not reaching remission in the first 2 rounds, fewer than 1 in 5 became symptom-free after switching to a third medication (Fava M et al. Am J Psychiatry. 2006;163[7]:1161-1172). Despite its utility, “ECT is widely stigmatized as a last-resort treatment,” said Fink, an ECT specialist for more than 50 years. The lack of required ECT instruction in US medical schools and psychiatry residency training programs, he said, has limited practitioners' ability to recognize patients who may benefit from ECT (Fink M and Taylor MA. JAMA. 2007;298[3]:330-332). Major depressive disorder accounts for an estimated 70% to 80% of ECT use. National statistics for use of ECT are lacking; only a few states mandate reporting of this treatment. Safe method of delivery Safe method of delivery Today's techniques virtually eliminate the risk of fracture once associated with ECT-induced seizures, Fink said. A patient receiving ECT is first given general anesthesia and a muscle relaxant, as well as ventilation with oxygen. Two electrodes then are placed on the scalp, either on both temples (bilateral ECT) or on the nondominant temple and near the vertex on the same side (unilateral ECT). Safe method of delivery The patient receives a brief-pulse electrical stimulus that causes a seizure in the brain lasting about 1 minute. The patient's body does not convulse. The patient awakens in 5 to 10 minutes. A course of ECT usually consists of 6 to 12 treatments, given 3 times a week for 2 to 4 weeks. The effects of different energy dosing and electrode placement are debated. Safe method of delivery Patients with severe depression often show substantial clinical improvement after only a few ECT treatments. By contrast, patients taking antidepressant medications may not start to feel better for several weeks. Continuation treatment with ECT and / or antidepressant medications commonly is required to maintain remissions. Forgetfulness of things past Forgetfulness of things past “We inform patients that ECT may make them forget how depressed they were when they entered the hospital, and that they may lose memory for facts, events, and names learned around the time of their ECT treatment,” said Raymond DePaulo Jr, MD, professor and chair of psychiatry and behavioral sciences at the Johns Hopkins University School of Medicine, in Baltimore, Md. “We explain that the ability to remember returns, but some memories may not come back,” he added. Forgetfulness of things past For many patients, memory loss is the most vexing adverse effect of ECT, said Sarah Lisanby, MD, director of the Division of Brain Stimulation and Therapeutic Modulation at New York State Psychiatric Institute and associate professor of clinical psychiatry at Columbia University College of Physicians and Surgeons. Forgetfulness of things past Lisanby and colleagues studied 55 patients with major depression who were randomly assigned to receive either right unilateral ECT or bilateral ECT, at either a low or high electrical dosage. The researchers found that unilateral electrode placement preserved memories better than bilateral placement, independent of electrical dosage and clinical outcome. Most patients had greater and more persistent loss of memory for public events than for personal experiences (Lisanby SH et al. Arch Gen Psychiatry. 2000;57[6]:581-590). Novel stimulation techniques Novel stimulation techniques While striving to improve ECT's efficacy and reduce its adverse effects, researchers also are seeking better ways to modulate and improve brain function, said Lisanby, who chairs the APA's Committee on ECT and Related Electromagnetic Therapies. Novel stimulation techniques Electrical stimulation techniques developed in the past 2 decades allow exploration of neural circuitry underlying both normal and abnormal brain function, she noted. They vary in their degree of invasiveness; some do not involve induction of seizures. As treatments, these techniques generally remain investigational. Novel stimulation techniques Vagus nerve stimulation (VNS) uses a pacemaker surgically implanted in the chest and connected to the left vagus nerve in the neck to regulate nerve impulses going to the brain. VNS does not cause a seizure. There is no evidence that it causes any measurable memory loss, Lisanby said. While only about 30% of patients with depression show an acute positive response to VNS, she said, it may help prevent relapses over the long term (Sackeim HA et al. Int J Neuropsychopharmacol. doi:10.1017/S1461145706007425 [published online ahead of print February 9, 2007]). Novel stimulation techniques In 1997, the US Food and Drug Administration (FDA) approved VNS for treatment of refractory epilepsy; some patients using it reported improved mood. In 2005, the FDA approved VNS for use in patients with refractory major depressive disorder. However, the Centers for Medicare & Medicaid Services concluded that VNS is not reasonable and necessary for the treatment of resistant depression and issued a national noncoverage determination for this indication, effective May 4, 2007 (http://www.cms.hhs.gov/MLNMattersArticles/downloads/MM5612.pdf). Novel stimulation techniques Transcranial magnetic stimulation (TMS) uses rapidly alternating magnetic fields applied to the scalp to induce small electrical currents in regions of the prefrontal cortex thought to be crucial to the antidepressant response. It can be focused on regions as small as 0.5 cm in diameter, largely sparing deeper brain structures implicated in ECT's amnestic effects. The technique does not require anesthesia and does not cause a seizure when given at doses within the safety guidelines. Novel stimulation techniques A 23-site trial, sponsored by Neuronetics Inc (Malvern, Pa), a TMS device manufacturer, found active TMS superior to sham TMS in 301 patients with treatment-resistant depression. The FDA is reviewing results of the trial, said Lisanby, principal investigator of Columbia University's site. This study found no measurable memory loss in patients receiving TMS (O’Reardon JP et al. Biol Psychiatry. doi:10.1016/j.biopsych.2007.01 .018 [published online ahead of issue June 13, 2007]). Novel stimulation techniques Magnetic seizure therapy (MST) involves use of TMS at a dosage high enough to induce a focal seizure. MST requires anesthesia. In their first trial of MST's safety and feasibility in treating patients with major depression, Lisanby and colleagues found it had a better acute safety profile with less memory loss than ECT (Lisanby SH et al. Neuropsychopharmacology. 2003;28[10]:1852-1865). Their study of MST's efficacy is under way. Novel stimulation techniques Transcranial direct current stimulation (tDCS) uses very weak electrical fields through the scalp to alter firing rates of cortical neurons. Depending on the direction of current flow, tDCS can either inhibit or facilitate function. It does not require anesthesia and does not cause a seizure. Pilot studies suggest tDCS may have antidepressant effects (Boggio PS et al. Int J Neuropsychopharmacol. doi:10.1017/S1461145707007833 [published online ahead of issue June 11, 2007]). Novel stimulation techniques Deep brain stimulation (DBS) requires surgical implantation of small electrodes in the brain to stimulate regions too deep to reach from the scalp. Already approved to treat Parkinson disease, DBS can be used to alter neural circuits as symptoms change. Its invasiveness, Lisanby said, may limit its use to patients with severe treatment-resistant depression (Mayberg HS et al. Neuron. 2005;45[5]:651-660). Further Resources Further Resources American Psychiatric Association Task Force. The Practice of Electroconvulsive Therapy: Recommendations for Treatment, Training, and Privileging. 2nd ed. Arlington, VA: American Psychiatric Publishing Inc; 2001. Further Resources Fink M. Electroshock: Healing Mental Illness. New York NY: Oxford University Press; 2002. Further Resources Lisanby SH, ed. Brain Stimulation in Psychiatric Treatment. Arlington, VA: American Psychiatric Publishing Inc; 2004. Further Resources George MS, Belmaker RH, eds. Transcranial Magnetic Stimulation in Clinical Psychiatry. Arlington, VA: American Psychiatric Publishing Inc; 2007. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png JAMA American Medical Association

Interest Surging in Electroconvulsive and Other Brain Stimulation Therapies

JAMA , Volume 298 (10) – Sep 12, 2007

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American Medical Association
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Copyright © 2007 American Medical Association. All Rights Reserved.
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0098-7484
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1538-3598
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10.1001/jama.298.10.1147
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Abstract

San Diego—A course of electroconvulsive therapy (ECT) every 9 or 10 months keeps her cyclic depression at bay, Kitty Dukakis said in an invited lecture at the annual meeting of the American Psychiatric Association (APA) here in May. Dukakis, the wife of former Massachusetts governor and 1988 Democratic presidential nominee Michael Dukakis, hopes her candor will help counter inaccurate and harrowing portrayals of ECT, such as those in the 1975 film One Flew Over the Cuckoo's Nest, based on Ken Kesey's 1962 novel. Although studies have demonstrated that electroconvulsive therapy (ECT) is an effective and safe treatment for severe major depression, inaccurate perceptions of ECT contribute to lingering stigma and fear regarding its use. (Photo credit: Will McIntyre/www.sciencesource.com) “Patients who are not helped by antidepressant medications and psychotherapy should not have to suffer for months, and in some cases, years, without ECT being an option,” noted Dukakis, who said she first received ECT in 2001, after experiencing deepening “bouts of despair” over 2 decades. Now 70 years old, she details her depression and its treatment, along with her earlier dependence on alcohol and amphetamine diet pills, in Shock: The Healing Power of Electroconvulsive Therapy (New York, NY: Avery; 2006), written with medical journalist Larry Tye. Dukakis' willingness to speak out has helped boost public and physician awareness of ECT's safety and efficacy, said Max Fink, MD, professor emeritus of psychiatry and neurology at the Stony Brook University School of Medicine, Stony Brook, NY. Results from 2 recent multisite collaborative studies also are prompting increased use of ECT worldwide, Fink noted. Remissions occurred with ECT in 86% of 394 patients with major depressive disorder completing the Consortium for Research in ECT study (Kellner CH et al. Arch Gen Psychiatry. 2006;63[12]:1337-1344) and in 55% of 290 patients completing a multisite study led by researchers at the New York State Psychiatric Institute and Columbia University College of Physicians and Surgeons, in New York City (Sackeim HA et al. JAMA. 2001;285[10]:1299-1307). These rates compare favorably with those obtained from use of antidepressant medications in similar patients. In the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial—the first study to examine the effectiveness of medication and other treatment for patients who did not become symptom-free after initial medication—about 30% of patients initially treated with citalopram experienced a remission. Among 727 patients whose symptoms did not remit with citalopram or who could not tolerate it, remission occurred in about 1 in 4 patients given either bupropion, sertraline, or venlafaxine. Thus, STAR*D patients had about a 55% chance of achieving remission with their first or second course of medication (Rush AJ et al. N Engl J Med. 2006;354[12]:1231-1242). However, among 235 patients not reaching remission in the first 2 rounds, fewer than 1 in 5 became symptom-free after switching to a third medication (Fava M et al. Am J Psychiatry. 2006;163[7]:1161-1172). Despite its utility, “ECT is widely stigmatized as a last-resort treatment,” said Fink, an ECT specialist for more than 50 years. The lack of required ECT instruction in US medical schools and psychiatry residency training programs, he said, has limited practitioners' ability to recognize patients who may benefit from ECT (Fink M and Taylor MA. JAMA. 2007;298[3]:330-332). Major depressive disorder accounts for an estimated 70% to 80% of ECT use. National statistics for use of ECT are lacking; only a few states mandate reporting of this treatment. Safe method of delivery Safe method of delivery Today's techniques virtually eliminate the risk of fracture once associated with ECT-induced seizures, Fink said. A patient receiving ECT is first given general anesthesia and a muscle relaxant, as well as ventilation with oxygen. Two electrodes then are placed on the scalp, either on both temples (bilateral ECT) or on the nondominant temple and near the vertex on the same side (unilateral ECT). Safe method of delivery The patient receives a brief-pulse electrical stimulus that causes a seizure in the brain lasting about 1 minute. The patient's body does not convulse. The patient awakens in 5 to 10 minutes. A course of ECT usually consists of 6 to 12 treatments, given 3 times a week for 2 to 4 weeks. The effects of different energy dosing and electrode placement are debated. Safe method of delivery Patients with severe depression often show substantial clinical improvement after only a few ECT treatments. By contrast, patients taking antidepressant medications may not start to feel better for several weeks. Continuation treatment with ECT and / or antidepressant medications commonly is required to maintain remissions. Forgetfulness of things past Forgetfulness of things past “We inform patients that ECT may make them forget how depressed they were when they entered the hospital, and that they may lose memory for facts, events, and names learned around the time of their ECT treatment,” said Raymond DePaulo Jr, MD, professor and chair of psychiatry and behavioral sciences at the Johns Hopkins University School of Medicine, in Baltimore, Md. “We explain that the ability to remember returns, but some memories may not come back,” he added. Forgetfulness of things past For many patients, memory loss is the most vexing adverse effect of ECT, said Sarah Lisanby, MD, director of the Division of Brain Stimulation and Therapeutic Modulation at New York State Psychiatric Institute and associate professor of clinical psychiatry at Columbia University College of Physicians and Surgeons. Forgetfulness of things past Lisanby and colleagues studied 55 patients with major depression who were randomly assigned to receive either right unilateral ECT or bilateral ECT, at either a low or high electrical dosage. The researchers found that unilateral electrode placement preserved memories better than bilateral placement, independent of electrical dosage and clinical outcome. Most patients had greater and more persistent loss of memory for public events than for personal experiences (Lisanby SH et al. Arch Gen Psychiatry. 2000;57[6]:581-590). Novel stimulation techniques Novel stimulation techniques While striving to improve ECT's efficacy and reduce its adverse effects, researchers also are seeking better ways to modulate and improve brain function, said Lisanby, who chairs the APA's Committee on ECT and Related Electromagnetic Therapies. Novel stimulation techniques Electrical stimulation techniques developed in the past 2 decades allow exploration of neural circuitry underlying both normal and abnormal brain function, she noted. They vary in their degree of invasiveness; some do not involve induction of seizures. As treatments, these techniques generally remain investigational. Novel stimulation techniques Vagus nerve stimulation (VNS) uses a pacemaker surgically implanted in the chest and connected to the left vagus nerve in the neck to regulate nerve impulses going to the brain. VNS does not cause a seizure. There is no evidence that it causes any measurable memory loss, Lisanby said. While only about 30% of patients with depression show an acute positive response to VNS, she said, it may help prevent relapses over the long term (Sackeim HA et al. Int J Neuropsychopharmacol. doi:10.1017/S1461145706007425 [published online ahead of print February 9, 2007]). Novel stimulation techniques In 1997, the US Food and Drug Administration (FDA) approved VNS for treatment of refractory epilepsy; some patients using it reported improved mood. In 2005, the FDA approved VNS for use in patients with refractory major depressive disorder. However, the Centers for Medicare & Medicaid Services concluded that VNS is not reasonable and necessary for the treatment of resistant depression and issued a national noncoverage determination for this indication, effective May 4, 2007 (http://www.cms.hhs.gov/MLNMattersArticles/downloads/MM5612.pdf). Novel stimulation techniques Transcranial magnetic stimulation (TMS) uses rapidly alternating magnetic fields applied to the scalp to induce small electrical currents in regions of the prefrontal cortex thought to be crucial to the antidepressant response. It can be focused on regions as small as 0.5 cm in diameter, largely sparing deeper brain structures implicated in ECT's amnestic effects. The technique does not require anesthesia and does not cause a seizure when given at doses within the safety guidelines. Novel stimulation techniques A 23-site trial, sponsored by Neuronetics Inc (Malvern, Pa), a TMS device manufacturer, found active TMS superior to sham TMS in 301 patients with treatment-resistant depression. The FDA is reviewing results of the trial, said Lisanby, principal investigator of Columbia University's site. This study found no measurable memory loss in patients receiving TMS (O’Reardon JP et al. Biol Psychiatry. doi:10.1016/j.biopsych.2007.01 .018 [published online ahead of issue June 13, 2007]). Novel stimulation techniques Magnetic seizure therapy (MST) involves use of TMS at a dosage high enough to induce a focal seizure. MST requires anesthesia. In their first trial of MST's safety and feasibility in treating patients with major depression, Lisanby and colleagues found it had a better acute safety profile with less memory loss than ECT (Lisanby SH et al. Neuropsychopharmacology. 2003;28[10]:1852-1865). Their study of MST's efficacy is under way. Novel stimulation techniques Transcranial direct current stimulation (tDCS) uses very weak electrical fields through the scalp to alter firing rates of cortical neurons. Depending on the direction of current flow, tDCS can either inhibit or facilitate function. It does not require anesthesia and does not cause a seizure. Pilot studies suggest tDCS may have antidepressant effects (Boggio PS et al. Int J Neuropsychopharmacol. doi:10.1017/S1461145707007833 [published online ahead of issue June 11, 2007]). Novel stimulation techniques Deep brain stimulation (DBS) requires surgical implantation of small electrodes in the brain to stimulate regions too deep to reach from the scalp. Already approved to treat Parkinson disease, DBS can be used to alter neural circuits as symptoms change. Its invasiveness, Lisanby said, may limit its use to patients with severe treatment-resistant depression (Mayberg HS et al. Neuron. 2005;45[5]:651-660). Further Resources Further Resources American Psychiatric Association Task Force. The Practice of Electroconvulsive Therapy: Recommendations for Treatment, Training, and Privileging. 2nd ed. Arlington, VA: American Psychiatric Publishing Inc; 2001. Further Resources Fink M. Electroshock: Healing Mental Illness. New York NY: Oxford University Press; 2002. Further Resources Lisanby SH, ed. Brain Stimulation in Psychiatric Treatment. Arlington, VA: American Psychiatric Publishing Inc; 2004. Further Resources George MS, Belmaker RH, eds. Transcranial Magnetic Stimulation in Clinical Psychiatry. Arlington, VA: American Psychiatric Publishing Inc; 2007.

Journal

JAMAAmerican Medical Association

Published: Sep 12, 2007

Keywords: brain stimulation,seizures,psychiatry

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