Electroconvulsive Therapy and Newer Modalities for the Treatment of Medication-Refractory Mental Illness
From the Department of Psychiatry and
Psychology, Mayo Clinic, Rochester, Minn. A question-and-answer section
appears at the end of this article. Individual reprints of this article are not available. Address correspondence to Keith G. Rasmussen, MD, Department of Psychiatry and Psychology, Mayo Clinic, 200 First St SW, Rochester, MN 55905 (e-mail: rasmussen.keith@mayo.edu).
Severe mental illnesses often remain chronic and refractory to medication, leading to substantial morbidity and mortality. For more than 60 years, electroconvulsive therapy has been the only nonpharmacological psychiatric procedure available to treat severe or medication-refractory major depressive disorder and other psychiatric conditions. Memory dysfunction remains the most serious ad verse effect, and current research focuses on attempts to ameliorate this complication. Transcranial magnetic stimulation and vagus nerve stimulation, 2 new neuropsychiatric technologies, are emerging as possible additions to our therapeutic armamentarium. Besides providing therapeutic benefits, these 3 methods may help elucidate the pathophysiology of psychiatric illness. Mayo Clin Proc. 2002;77:552-556
The use of chemically induced seizures for treatment of mental disorders is documented in various reports dating back centuries.1 The first systematic descriptions of convulsive therapy were provided in 1934 by Ladislaus von Meduna, who used injections of camphor liniment to induce seizures in patients with schizophrenia, many of whom responded dramatically.1 His technique was quickly recognized for its value in psychiatric therapeutics and was adopted worldwide within a few years of its introduction. Other chemicals, such as pentylenetetrazol, were also used to induce seizures. This pharmacoconvulsive therapy, although beneficial, was fraught with problems, such as unreliable induction of seizures, and was frightening to patients. Thus, when Cerletti and Bini introduced the technique of electrically induced seizures in 1938, it was welcomed and quickly became the preferred method.1
Several aspects of the ECT technique affect efficacy and adverse effects. The most prominently studied is the site of stimulus electrode placement on the head (Figure 1). The original placement was bilateral, in which each electrode is placed on the temporal fossa on each side of the head (the so-called bitemporal position). One alternative placement currently in use is the unilateral position, in which 1 electrode is placed on the temporal fossa on the right side as in the bitemporal position, but the other electrode is placed just to the right of the vertex of the head. In this placement, the electrical current is concentrated away from the language areas on the left side of the brain, thus lessening the memory impairment that is common with ECT (see subsequent discussion). Another electrode placement, also designed to lessen ECT-induced memory impairment, is bifrontal, in which the electrodes are placed on either side of the forehead. In this placement, electrical current is concentrated away from mesial temporal lobe structures involved with memory formation. Whether the well-known therapeutic efficacy of traditional bitemporal ECT is preserved with unilateral or bifrontal ECT is unclear. A second technical factor is the dose of electrical charge used during ECT. Typical electrical doses used in ECT range from 25 to 504 mC, most of which is shunted across the scalp and does not reach the brain. The electrical dose may affect both therapeutic efficacy and cognitive adverse effects. For example, in unilateral ECT, giving a dose of electricity barely enough to induce a seizure (the seizure threshold) is associated with low therapeutic efficacy, whereas giving too much electrical charge results in excessive cognitive dysfunction.2 Precise quantification of the electrical dose ensures that the correct amount is administered. A third technical issue in ECT concerns treatment frequency. Usually in the United States, treatment frequency is thrice weekly, but several studies have shown that twice weekly may yield equivalent therapeutic benefit (albeit more slowly) with much less cognitive impairment.1The choice of electrode placement, stimulus dose, and treatment frequency is individualized and depends on such factors as patient age and severity of illness. Indications Electroconvulsive therapy is the most effective treatment for major depression, with average response rates of 70% to 90% compared with about 60% to 70% for antidepressant medications.1 It is given to patients whose condition is refractory to or who are intolerant of antidepressant medications, who are so ill (eg, suicidal, catatonically stuporous, refusing food and fluids) that the most rapid treatment is needed, or who express preference for it based on past experience.3 Additionally, ECT is highly effective for mania and certain cases of schizophrenia.3 An intriguing series of reports suggests that ECT can help ameliorate the motor symptoms of Parkinson disease and various other movement disorders, such as tardive dystonia, tardive dyskinesia, and neuroleptic-induced malignant catatonia (also termed neuroleptic malignant syndrome).1 Risks and Adverse Effects Electroconvulsive therapy is actually a safe procedure. In fact, the death rate due to treatment is approximately 1 per 10,000 patients.1 Although ECT has no absolute contraindications, relative contraindications include presence of brain tumor with increased intracranial pressure, unstable myocardial function, and American Society of Anesthesiology risk level 4 or 5.3 During the seizure, heart rate and blood pressure increase sharply. Thus, patients with cardiac disease, such as coronary atherosclerosis, congestive heart failure, or cardiac dysrhythmias, have a higher risk of cardiovascular complications. Therefore, any patient with suspected unstable or untreated cardiac illness should undergo evaluation before ECT. Additionally, any unstable vascular malformation, such as an arteriovenous fistula or a leaky aneurysm, would be at risk of rupture during ECT. Thorough evaluation and stabilization of any existing cardiovascular condition before treatment make ECT safe even for many patients with advanced disease. For patients with a known increase in intracranial pressure, such as those with brain tumors, ECT is relatively contraindicated.3 However, ECT has been used safely in patients with various neurologic conditions, such as dementia and epilepsy. In contrast to the rarity of medical complications associated with ECT, memory disturbance of varying severity is common and is by far the most bothersome adverse effect. Electroconvulsive therapy–induced memory impairment takes 3 forms. The first is posttreatment confusion. Typically, it takes a few minutes to half an hour for a patient to become fully alert and oriented after treatment. Occasionally, especially in elderly patients receiving thrice-weekly treatment with bitemporal electrode placement, the period of posttreatment confusion persists for several hours or even days. This interictal delirium is reversible with cessation of treatment. The second type of memory impairment with ECT is anterograde amnesia. This refers to the inability to recall information learned after the treatments have begun. An example is when a patient has a conversation with somebody early in the day and then forgets it later on that day. Extensive research has documented that ECT-induced anterograde amnesia is temporary.2 The third and most bothersome type of ECT-induced memory impairment is retrograde amnesia, forgetting things that happened before the course of treatments. An example is forgetting a movie that was seen a week before the first treatment. Events of several months before treatment are most likely forgotten. Usually, only a few events, such as conversations, are forgotten, but patients occasionally forget most of the events of this period. Additionally, patients sometimes have sporadic episodes of forgetting personal life events that happened several years before treatment. Some of the forgotten events may never be remembered. Thus, during the informed consent process, it is important to discuss this issue with patients and to monitor their memory function during the course of treatments. Mechanism of Action The precise mechanism of action of ECT is unknown. Traditional theories have been based on neurotransmitter and neuroreceptor studies in animals and probably have limited utility in extrapolation to humans. However, some of the consistent findings in the animal literature include down-regulation of postsynaptic β-receptors and up-regulation of postsynaptic serotonin type 2 receptors.1 An intriguing finding in humans is that potent reduction of cerebral blood flow in the frontal lobes along with induced slowing of EEG frequencies in the same region correlates strongly with therapeutic outcome in ECT.4,5 Thus, the effects of treatments on frontal lobe function, an area implicated in the pathophysiology of depressive illness, may be relevant in the mechanism of action of ECT. Current Research A particularly common problem in ECT practice is the high relapse rates of depressive illness after a successful course of treatments.6Standard practice is to give patients antidepressant medications after ECT. Another strategy is continuation and maintenance ECT, in which treatments are continued at spaced intervals (eg, weekly, biweekly, or monthly) for a few months or even years after the successful treatment sessions. Current research is elucidating treatment strategies to prevent relapse of depression after ECT. Another common problem is memory impairment. Current ECT research is evaluating alternative electrode placements to lessen ECT-induced cognitive adverse effects. For example, the bifrontal placement allows the electrical current to be concentrated in the frontal lobes, where clinical efficacy may be most important, but bypasses the mesial temporal lobes, areas thought to be most critical for memory impairment. An exciting area of ECT research involves the use of sophisticated brain imaging (eg, positron emission tomography and single-photon emission computed tomography) and computerized EEG technology to elucidate the mechanism of action of ECT and even the neurobiological basis of depressive illness. As mentioned previously, successful courses of ECT produce sharp (although reversible) reductions of cerebral blood flow in the frontal lobes as well as induction of delta and theta EEG activity in the same region.4,5 Additionally, computer analysis of the EEG during ECT seizures is helping to distinguish therapeutic from nontherapeutic treatments.7 This line of inquiry should help us understand brain mechanisms in the action of ECT and may help lead to other treatment technologies. Because ECT involves repeated administrations of general anesthesia, some risk of medical complications, and memory impairment, less invasive neuropsychiatric treatments are needed. The 2 emerging technologies that appear promising are transcranial magnetic stimulation (TMS) and vagus nerve stimulation (VNS). A novel and safe method of brain stimulation first used in 1985, TMS consists of applying magnetic fields to the brain through a metal coil placed over the cranium.8 During a typical TMS session, the patient sits comfortably awake throughout the whole procedure. It was first used clinically to stimulate the motor cortex to record electromyographic activity in certain muscle groups to test the integrity of the motor pathways, analogous to the use of evoked potentials to test the integrity of sensory pathways. Transcranial magnetic stimulation can be used to study cortical neurophysiology or as a possible therapeutic intervention for psychiatric disorders. In recent years, much excitement has developed regarding the possibility that TMS can treat depression.8 In contrast to ECT, TMS requires no anesthesia, does not induce seizures, and does not appear to cause cognitive deficits. Studies directly comparing ECT to TMS are limited thus far but suggest comparable antidepressant efficacy.9 At publication of this article, TMS has not been approved for the treatment of depression. Based on early work in animals showing that electrical stimulation of the vagus nerve stopped seizures in dogs, an implantable device capable of stimulating the vagus nerve in humans was developed and studied. Vagus nerve stimulation involves implantation of an electrical generator (about the size and shape of a cardiac pacemaker) into the left chest wall. This is connected to a wire, which in turn is connected to the vagus nerve in the neck. An implantable vagus nerve stimulator (NeuroCybernetic prosthesis [Cyberonics, Inc, Houston, Tex]) is now commercially available, has been approved by the Food and Drug Administration for medication-refractory partial-onset epilepsy, and has been implanted in thousands of humans. The function of the electrical generator, including modification of the intensity of electrical stimulation to the vagus, is monitored and modified by a portable wand connected to a computer and held over the generator site above the skin noninvasively. Long-term safety has been established. This stimulator has been successful in patients with refractory epilepsy and has been found to be safe and effective by the American Academy of Neurology.10 Based on apparent antidepressant activity in epileptic patients and effects of VNS on cortical blood flow and neurochemistry that are similar to the effects of antidepressant treatments, a preliminary open trial of VNS in patients with medication-refractory depression was undertaken, and it was found to be successful in a substantial proportion.11 At publication of this article, the NeuroCybernetic prosthesis has not been approved by the Food and Drug Administration for the treatment of depression. Questions About Treatment of Medication-Refractory Mental Illness 1. Which one of the following most likely indicates further medical investigation before clearance for ECT?
2. Which one of the following most appropriately indicates referral for ECT?
3. Which one of the following is not true regarding the memory disturbances caused by ECT?
4. Which one,of the following is true about TMS?
5. Which one of the following is true regarding VNS?
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