Electroconvulsive Therapy: What the Internist Needs to Know

REVIEW

MAYUR PANDYA, DO LEOPOLDO POZUELO, MD DONALD MALONE, MD* CME Psychiatric Neuromodulation Center, Section Head, Consultation Liaison Psychiatry, Section Head, Adult Psychiatry, Medical CREDIT Cleveland Clinic Department of Psychiatry and Psychology, Director, Psychiatric Neuromodulation Center, Cleveland Clinic Cleveland Clinic

Electroconvulsive therapy: What the internist needs to know

■ ABSTRACT LECTROCONVULSIVE THERAPY (ECT) has E an undeservedly bad reputation. This is Although electroconvulsive therapy (ECT) is widely used unfortunate. As currently performed, ECT is to treat a number of psychiatric disorders, many safe and is effective for treating a number of physicians are still unfamiliar with the procedure, its psychiatric disorders. For some patients, it is indications, and its contraindications. This article is an the only therapy that works. internist’s guide to ECT, with particular focus on how The following article outlines the indica- commonly prescribed medications and medical conditions tions for and contraindications to ECT and spe- affect ECT. cial considerations for patients referred for it. ■ KEY POINTS ■ TREATING MENTAL ILLNESS BY INDUCING SEIZURES ECT is safe and works rapidly, making it a primary therapy in situations requiring acute intervention. Another In 1927, Wagner-Jauregg won the Nobel Prize reason to consider ECT is a history of poor response to for curing patients with “dementia paralytica” medications or of adverse effects with medications. (tertiary syphilis) by infecting them with malaria. The concept that one illness could be treated by inducing another led von Meduna Although ECT was first used in patients with in 1934 to perform the first reported convul- schizophrenia, it is most often used today for mood sive therapy in psychiatry.1 disorders, including unipolar depression, bipolar Von Meduna, a neuropathologist, had depression, and acute mania. noted that patients with epilepsy had more glial cells than average, and patients with Before ECT is performed, patients require a medical schizophrenia had fewer. He had also seen evaluation to undergo anesthesia, and some may need data that few patients had both schizophrenia special consultation. and epilepsy (not true), and that when people with mental disorders suffered seizures, their Vagus nerve stimulation is the newest neuromodulatory mental condition often improved. He rea- technique to receive approval for adjunctive treatment of soned that if he could induce seizures in depression. Experimental treatments that show promise patients with schizophrenia by injecting cam- phor, their glial cells might increase, and their include deep brain stimulation and repetitive transcranial symptoms might improve. And in fact, in his magnetic stimulation. initial work, symptoms of schizophrenia improved partially to completely. In 1938, the Italians Bini and Cerletti performed the first documented electrical induction of seizures in humans.2 One year later, ECT was introduced to the United *Dr. Malone has obtained research funding from and is a consultant for Medtronic, Inc. States. Until effective antipsychotic drugs

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were developed in the 1950s, the only effec- resulting in interpersonal and financial dis- tive alternatives to ECT were insulin shock tress. According to the Global Burden of therapy and lobotomy, which was falling out Disease Study, depression ranks as the fourth- of favor. leading cause of disability worldwide.8 Initial In the early years, the lack of adequate therapies consist of drugs and psychotherapy, anesthesia or muscle relaxation resulted in alone or in combination. Patients with depres- fractures or dislocations, often with negative sion that is moderate to severe and resistant to recollection for the event. Lack of knowledge drug treatment may be referred for ECT, regarding the dose parameters of electrical which is often considered the gold standard stimulation led to more cognitive side effects. antidepressant treatment. Over the decades, the safety and efficacy Most patients should undergo an adequate of ECT have been improved and its indica- trial of oral drug therapy before being referred tions have been defined. Today, it is usually for ECT. The actual number of drugs that done with the patient under general anesthe- should be tried and for how long are deter- sia, and with muscle relaxants and cardiopul- mined on a case-by-case basis; in general, one monary monitoring, which have reduced its should try different classes of antidepressants complications. Nevertheless, ECT’s historical and various augmentation techniques before beginnings, combined with its negative por- turning to ECT. Poor response to medications trayal in the media,3 have left some patients or adverse effects with pharmacotherapy may fearful and hesitant to undergo ECT if they be reasons to consider ECT. need it. On the other hand, ECT’s safety and rapid efficacy make it a good primary treatment in How ECT works is unknown situations requiring acute intervention, such Although many mechanisms have been pro- as catatonia and psychiatric exacerbations posed, how ECT works remains unknown. An during pregnancy. attractive hypothesis to account for ECT’s All patients being considered for ECT effects on depression is that it alters serotonin should receive a general psychiatric evalua- ECT is far and dopamine activity.4,5 Changes in gamma- tion. The psychiatrist will then proceed with safer now aminobutyric acid (GABA) and noradrena- referral for ECT if appropriate and recom- line levels have also been reported.4,6 Most mend any necessary workup (discussed than in the past likely, the therapeutic effects of ECT are a below). result of a combination of neurotransmitter alterations. ■ ECT REQUIRES MEDICAL ASSESSMENT

■ MOST OFTEN USED Although no absolute contraindications to FOR MOOD DISORDERS ECT exist, several conditions are associated with an increased risk of complications and ECT was first used in patients with schizo- even death (see below). The cardiovascular, phrenia, and today, treatment-resistant psy- central nervous, and pulmonary systems carry chosis is still considered an appropriate indica- the highest risks from general anesthesia and tion for it. Today, however, ECT is most often the induction of generalized seizure activity. used for mood disorders, including unipolar In most routine cases, the patient under- depression, bipolar depression, and acute goes routine clearance for anesthesia, but spe- mania. cial considerations may necessitate consulta- The Diagnostic and Statistical Manual of tion with medical specialists such as a cardiol- Mental Disorders defines major depression as a ogist, neurologist, neurosurgeon, endocrinolo- constellation of symptoms, which may include gist, anesthesiologist, or dentist. All cases depressed mood, anhedonia, sleep distur- referred for ECT require analysis of the med- bance, psychomotor retardation or agitation, ical risks of treatment (discussed below). fatigue, guilt, poor concentration, and suici- The pre-ECT evaluation includes basic dality.7 The symptoms result in marked social tests such as a complete blood cell count, and occupational impairment, commonly serum electrolyte levels, renal function tests,

680 CLEVELAND CLINIC JOURNAL OF MEDICINE VOLUME 74 • NUMBER 9 SEPTEMBER 2007 Downloaded from www.ccjm.org on October 1, 2021. For personal use only. All other uses require permission. and electrocardiography. Neuroimaging, chest TABLE 1 radiography, and spine films are not routinely done unless clinically indicated. For example, Conditions requiring special consideration spine films may be necessary in some patients before electroconvulsive therapy who are elderly or who have osteoporosis. Conditions associated with autonomic sensitivity Compression fractures are not an absolute Clinically evident hyperthyroidism contraindication to ECT, but the physician Decompensated congestive heart failure performing ECT would want this information Elevated intracranial pressure so that he or she can make sure to provide Fragile aneurysm adequate paralysis. Careful attention should Narrow-angle or closed-angle glaucoma also be paid to the teeth, with dental consul- Pheochromocytoma tation obtained if needed. Recent myocardial infarction Before ECT, electrolyte levels should be Recent stroke stabilized and appropriate fluid status main- Severe valvular disease Significant arrhythmia tained. Uncontrolled hypertension Unstable angina ■ SOME ECT PATIENTS NEED SPECIAL CONSIDERATION Conditions associated with sensitivity to anesthesia Amyotrophic lateral sclerosis According to the American Psychiatric Genetic or acquired pseudocholinesterase deficiency Myasthenia gravis Association’s Task Force on Electroconvulsive Neuroleptic malignant syndrome 9 Therapy, patients with certain medical con- Porphyria ditions may require more extensive workup Pregnancy and consideration during ECT (TABLE 1). Conditions associated with cognitive sensitivity Patients with autonomic sensitivity Dementia Traumatic brain injury Seizure induction causes acute cardiopulmonary changes, including some initial parasympathetic bradycardia. This is followed by a sympathetic surge, causing transient tachycardia and hyper- and giving an antihypertensive agent (eg, tension. The sympathetic surge occurs only if a intravenous labetalol or esmolol) during the seizure is induced. Thus, patients at risk of brady- procedure to blunt the sympathetic response cardia (eg, those on beta-blockers) may be par- in patients at high risk. ticularly prone if stimulation is given but a Patients with chronic atrial fibrillation seizure is not induced. To counteract the can undergo ECT safely. Therapeutic antico- parasympathetic effect, some physicians give an agulation should be continued throughout the anticholinergic drug—atropine or glycopyrro- ECT course. late (Robinul)—although this is not routine or Other conditions that pose increased risk required. are clinically evident hyperthyroidism (in These autonomic effects make patients which ECT may result in thyroid storm), with a number of cardiovascular and neuro- pheochromocytoma, and narrow-angle or logic conditions particularly vulnerable to closed-angle glaucoma. However, ECT has exacerbation and increased risk of death. been successfully performed in all of the above These conditions include increased intracra- conditions, and therefore the condition alone nial pressure, recent stroke, recent myocar- should not exclude appropriate patients from dial infarction, unstable angina, uncon- ECT. trolled hypertension, severe valvular disease, A cardiology consultation is also recom- decompensated congestive heart failure, frag- mended for patients with pacemakers or ile aneurysm, and significant arrhythmia. implantable cardioverter-defibrillators (ICDs); Recommended management for patients these patients can undergo ECT safely if the with many of these conditions includes func- device has been checked recently. Depending tional cardiac testing before the procedure on the type of pacemaker, it may have to be

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T ABLE 2 Medications requiring special consideration before electroconvulsive therapy

MEDICATION POSSIBLE UNDESIRED EFFECT

Lidocaine Seizure inhibition Diabetic agents Hypoglycemia Theophylline Prolonged seizures, status epilepticus Antidepressants, mood stabilizers Carbamazepine (Carbatrol, Tegretol) Seizure inhibition (major effect) Gabapentin (Neurontin) Seizure inhibition (major effect) Lamotrigine (Lamictal) Seizure inhibition (minor effect) Lithium Delirium, prolonged seizures Monoamine oxidase inhibitors Hypertensive crisis Tricyclic antidepressants Cardiotoxicity Topiramate (Topamax) Seizure inhibition (minor effect) Valproic acid (Depakene) Seizure inhibition (major effect) Benzodiazepines Seizure inhibition, reduced efficacy, cognitive effects Anticholinesterases Prolonged anesthesia effect Herbal supplements Ginkgo biloba Increased intracranial pressure, cerebral hemorrhage Ginseng Parasympathetically mediated bradycardia St. John’s wort Prolonged anesthesia effect, cardiovascular collapse

Most patients adjusted, especially if the patient is pacemaker- During pregnancy, the risk of teratogene- should have an dependent. ICDs must be turned off immedi- sis with many oral psychotropic agents makes ately before the procedure, during which the ECT invaluable for the treatment of decom- adequate trial patient must be monitored electrocardiograph- pensated psychiatric conditions. Although of drug therapy ically. The ICD is turned back on when the ECT does pose risks (greatest during the first treatment is complete.10 trimester) and should be avoided if possible,11 before trying it can be safe and effective with proper prepa- ECT Patients with anesthesia sensitivity ration and monitoring, including a pelvic A pre-anesthesia consultation is indicated to examination, uterine tocodynamometry, address any cardiac, pulmonary, or other med- intravenous hydration, fetal cardiac monitor- ical risk factors that affect the risk of anesthe- ing, and avoidance of excessive hyperventila- sia and to determine whether the patient’s tion.12 The risk to the fetus is low because the medication regimen or the anesthetic tech- anesthetic doses are small, the patient receives nique need to be modified. the anesthetic for only a short time, and little The depolarizing muscle relaxants that are of it crosses the placenta. Similarly, breast- commonly used, such as succinylcholine, may feeding can continue during courses of ECT, pose risks of adverse effects in patients with since the concentrations of anesthetics in certain conditions, eg, myasthenia gravis, breast milk are low. amyotrophic lateral sclerosis, genetic or acquired pseudocholinesterase deficiency, and Patients with cognitive sensitivity neuroleptic malignant syndrome. In such con- Transient cognitive effects are a common side ditions, a substitute nondepolarizing agent effect of ECT. Although this can occur in may be indicated. Barbiturates are considered patients with normal cognitive function, the unsafe in patients with porphyria, who should risk is higher in patients with a history of brain receive alternative anesthetics. trauma or dementia. Cognitive effects include

682 CLEVELAND CLINIC JOURNAL OF MEDICINE VOLUME 74 • NUMBER 9 SEPTEMBER 2007 Downloaded from www.ccjm.org on October 1, 2021. For personal use only. All other uses require permission. Electroconvulsive therapy Baseline Induction Seizures continue Recovery

FIGURE 1. Electroencephalographic (EEG, top two lines); electromyelographic (EMG, foot lead, third line), and electrocardiographic (ECG, bottom line) monitoring during electroconvulsive therapy. At baseline, notice the EEG activity. At induction (time 0 seconds), the immediate spike of EEG activity documents seizures. EMG activity in the foot lead documents motor seizures. The heart rate is unchanged from baseline. As seizures continue, EEG activity continues, while motor seizures terminate at 26 seconds on the EMG lead. Tachycardia is evident on the ECG tracing. On recovery, EEG activity returns to baseline, indicating that the seizure is over, and the heart rate returns to baseline. The pre-ECT evaluation short-term retrograde and anterograde amne- ■ DRUG INTERACTIONS sia around the time of the procedure. includes a The risk is less if the electrodes are Several classes of medications need to be CBC count, placed unilaterally instead of on both sides of reduced in dosage or completely stopped the head. Because the response to unilateral before ECT. Some medications suppress electrolytes, treatment is believed to be correlated with seizure activity; others have synergistic effects renal function the dosage of stimulation above threshold, with ECT that can lead to serious complica- tests, and ECG we recommend dose titration to determine tions such as cardiotoxicity or prolonged the seizure threshold level and to assure seizures. For this reason, all cardioprotective appropriate but not excessive stimulation agents are usually continued during the course dosage. For bilateral treatment, this dose- of ECT. response relationship above threshold may • Lidocaine should be continued only in be less critical. life-threatening situations due to its anti- Another strategy to reduce cognitive convulsant effects. impairment may be to place the electrodes on • On the day of the procedure, hypo- both sides, but over the frontal lobes instead glycemic medications should be re- of the temporal lobes. Research on bifrontal duced or withheld until after the pro- placement is ongoing to determine if it mini- cedure, since patients must fast before mizes cognitive impact and if it is as effective ECT. as bitemporal placement.13,14 • Theophylline should be decreased in dose Cognitive impairment can also be reduced or discontinued, if possible, as it has been by scheduling longer intervals between treat- associated with prolonged seizures and ments. status epilepticus.

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• Mood stabilizers and sedative agents may ■ A COURSE OF ECT interfere with seizure activity, owing to IS SIX TO 10 TREATMENTS agonist effects on GABA. • Anticholinesterases and popular com- A typical course of ECT consists of six to 10 mon alternative and complementary treatments, scheduled at intervals of two or medications may carry risks as well (TABLE three times per week. The patient should start 2).15 to experience some improvement in psychiatric symptoms by the second or third treat- ■ THE PROCEDURE ment, with a full response by the fifth to 10th treatment. How many treatments are ulti- The ECT procedure involves coordinated care mately given is based upon clinical improve- between the anesthesiologist and psychiatrist. ment; treatments are stopped when the The goal of ECT is to produce a controlled patient no longer improves with successive and monitored seizure. It is most often per- treatments. formed in a postanesthesia care unit, with Many patients with severe refractory anesthesia and cardiac, hemodynamic, and depression begin ECT treatment while hospi- respiratory monitoring. talized. Those who have significant improve- General anesthesia is commonly ment quickly may be able to complete the achieved with methohexital or etomidate. ECT series on an outpatient basis. Once the patient is completely asleep, he or The series of six to 10 treatments is known she is given a muscle relaxant (almost always as the acute index series and typically is all succinylcholine). The goal is to cause signif- that is needed to lift the patient out of depres- icant muscle relaxation, especially if the sion. In contrast, 2 to 3 months are needed to patient has osteoporosis or a history of spinal achieve remission with standard antidepres- injury. Direct electrical stimulation of the sant therapy. Treatment with antidepressants, masseter muscles will bypass succinyl- mood stabilizers, or both should be resumed choline’s effect, so a bite block is inserted to immediately after the ECT series is done, as Antidepressant avoid oral injury. The anesthetist ventilates relapse rates greater than 80% have been drug therapy the patient with 100% oxygen under positive reported within 6 months in those not receiv- pressure. ing treatment (compared with 60% with nor- should resume Once anesthesia and muscle relaxation triptyline [Pamelor] and 39% with nortripty- immediately are achieved, the electrical stimulus is given. line and lithium in combination).16 Depending on the institution or physician, A subset of patients who have more after ECT to the stimulus is delivered either unilaterally or refractory mood disorders may need to contin- maintain bilaterally. The induced seizure usually lasts ue their ECT treatments in combination with remission 30 to 90 seconds (FIGURE 1). Seizures lasting maintenance medication. These are patients more than 120 seconds are commonly termi- who had relapses on medication alone and nated with intravenous benzodiazepines. needed another series of ECT as rescue thera- After the seizure is over, the patient usually py. After a response is achieved with ECT, the recovers in 5 to 15 minutes and does not treatments are tapered in frequency over the remember the treatment episode. Once next few weeks until they are given every cleared to leave the recovery area, the month. patient is taken back to his or her ward if an inpatient or sent home if an outpatient. ■ THE FUTURE (Many patients receive ECT on an outpatient basis and can be sent home approxi- Although ECT has been an effective treat- mately 1 hour after the procedure without ment for mood disorders, the search continues complications.) for better long-term psychiatric neuromodula- Common adverse effects include myalgias, tory techniques. The most promising treat- headache, nausea, and transient cognitive ments on the horizon include vagus nerve effects. Tardive seizures have been reported stimulation, deep brain stimulation, and but are extremely rare. repetitive transcranial magnetic stimulation.

684 CLEVELAND CLINIC JOURNAL OF MEDICINE VOLUME 74 • NUMBER 9 SEPTEMBER 2007 Downloaded from www.ccjm.org on October 1, 2021. For personal use only. All other uses require permission. Vagus nerve stimulation (by means of an sions, so it does not necessitate anesthesia and implanted pacemaker-type device) is the most therefore causes fewer side effects. However, it recent neuromodulatory technique to receive does not appear to work as well as ECT. US Food and Drug Administration (FDA) Deep brain stimulation is delivered via approval for adjunctive treatment of depres- electrodes implanted in precise areas of the sion. Its current indications require failure of brain, which are connected to an implanted treatment with four or more antidepressants. pacemaker-type device. It is also used in Symptoms improve gradually with time. Parkinson disease, but with the electrodes in Unlike ECT, vagus nerve stimulation is not different areas of the brain. Studies of its use in indicated for acute or emergency treatment. several psychiatric disorders were prompted by Repetitive transcranial magnetic stimula- observations in studies in which lesions were tion and deep brain stimulation have not yet surgically created in the brain. Of the experi- received FDA approval, but they appeared mental treatments, deep brain stimulation may promising in initial trials.17,18 Repetitive trans- hold the most promise because it is directed at cranial magnetic stimulation is delivered via precise targets in the brain and it has been suc- an induction coil, in brief daily sessions over a cessful in severe, refractory cases. However, its course of days to weeks. It has an advantage use remains investigational, and the results over ECT in that it does not induce convul- seen so far are highly preliminary. ■

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