Electroconvulsive modern psychiatry

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1 Electroconvulsive therapy (ECT) in modern psychiatry Eva Kos University of Zagreb, School of Medicine Anamarija Kruc University of Zagreb, School of Medicine Abstract Electroconvulsive therapy (ECT) is an example of a non-pharmacological treatment that is used to treat certain psychiatric disorders. Today, it is most commonly used to treat severe depressive episodes, but is also indicated for patients with psychosis, catatonia, bipolar disorder, neuroleptic malignant syndrome and others. During ETC, small amount of electrical current is passed through the brain which causes chemical changes in the brain. Safety and tolerability of ECT have been enhanced by using modified stimulation techniques and by progress in modern anesthesia. Due to high efficacy, side effects of the ECT, such as confusion, nausea and short-term memory loss, are practically negligible. Despite all of this, it continues to be the most stigmatized treatment not only in psychiatry, but in medicine in general. Keywords: BDNF, electroconvulsive therapy, mood disorders, psychiatry INTRODUCTION Electroconvulsive therapy (ECT) is the safe induction of a series of generalized epileptic seizures for therapeutic purposes, using brief-pulse stimulation techniques under anesthesia and muscle paralysis. Informed consent of the patient or the responsible legal guardian and Ethics Committee approval are obligatory. In the past decade, several large-scale studies have confirmed the significant superiority of ECT in the treatment of severe and refractory psychiatric conditions, such as major depressive disorder and bipolar disorder. However, although the technique and practice of ECT has improved considerably in the last decades, the crucial neurobiological mechanisms contributing to the therapeutic efficacy in distinct, psychiatric disorders are still under investigation. 1, 7 The aim of this article is to give a short overview and summarize the current knowledge of the role of ECT in the treatment of psychiatric disorders. HISTORY AND ETHICAL DILLEMAS Although being a great subject of controversy in medical and non-medical world, ECT is the only somatic therapy from the 30 s that remains in widespread use today. The idea of potential therapeutic effects of ECT dates back to 16th century, although we were not aware of its benefits in psychiatry. It all started when the Swiss alchemist Para celsus gave camphor by mouth to induce convulsions and cure lunacy. It was a method based on chemically induced convulsions. 1 Three centuries later, in 1934, Ladislaw Meduna, a Hungarian psychiatrist, investigated a hypothetical inverse relationship between seizures and schizophrenia. Hoping to cure patients with schizophrenia by inducing epilepsy, he injected camphor in oil into a patient with catatonic schizophrenia, causing a 60 second grand mal seizure. The patient went into a full recovery after a short series of such treatments. Camphor was later abandoned and metrazol was used instead, but as metrazol caused severely unpleasant sensations in patients treated with it, the concept of applying electricity to the heads of people with mental problems emerged. 1 The Italian scientists Cerletti and Bini were very successful in finding the right approach of how to apply electricity directly to the human scalp. In 1938, they treated an unidentified 39-year-old man who was found delusional in a train station. His delusions receded after several treatments; he recovered fully after 11 treatments without adverse effects. Thus electroconvulsive therapy was born and soon replaced metrazol therapy all over the world. It was cheaper, less frightening and more convenient. 1 It s been a long journey since, to get to where we are today. In 2001 the American Psychiatric Association released its latest Task Force report, which emphasizes the importance of informed consent, and the expanded role that ECT has in modern medicine

2 MISCONCEPTIONS CONCERNING ECT When most people think of ECT, the first thing that crosses their mind is an image of Jack Nicholson strapped-down helplessly, overwhelmed by pain. Is this really how it works and why does the public see it this way, as a barbaric and inhumane therapy? Misinformation and various representations in media, culture, arts and Internet have taken its toll on this subject. Even today, when we know how beneficial and low-risk ECT is, people (including medical professionals) tend to fear it, condemn it or dismiss it as a form of treatment. It is true, that in the past, it was often misused and applied without patients consent, controlling the patients for the benefits of the hospital staff. That is no longer an issue, since standards for informed consent were initially established in a 1978 report from an American Psychiatric Association (APA) Task Force and the World Health Organization in 2005 advised that ECT should be used only with the informed consent of the patient (or their guardian if their incapacity to consent has been established). 2 It is also true that poorly performed procedure, without proper anesthesia, oxygenation, and muscle relaxants, inevitably led to injuries. Nowadays, it is always performed with premedication in order to make the procedure as comfortable as possible. 3 Media, including films and literature often depicted ECT as a brutal and harmful method which left the treated patients mute, unable to perform any mentally demanding actions. The biggest impact made on the public was probably Milos Forman s 1973 film version of One Flew over the Cuckoo s Nest. On the other hand, Internet was a revolution for enlightenment of the public, providing evidence-based information that could finally take the stigma of ECT off. Unfortunately, it also gave rise to anti-ect lobbying often supported by medical professionals. 4 But what do the patients who underwent ECT say? Various research was done, both retrospective and prospective, to investigate patients subjective views of ECT. More than 80% of patients felt better and would be willing to have ECT again, if needed. The biggest problem they faced was memory loss, which was often transient, and was the reason why some of the patients feared ECT. 3, 4 PROCEDURE Electroconvulsive therapy implies use of the electric current that provokes generalized cerebral seizure, as a way of treatment in several psychiatric disorders. It is done under general anesthesia. 5 Pre-ECT evaluation. PRE- ECT evaluation includes taking a complete medical history with a particular attention paid to any history of cardiopulmonary and central nervous system disease. Appropriate physical examination and laboratory evaluation can be tailored to the patient s medical history, and should be used to identify the presence and severity of medical risk factors, so they could be treated. Mandatory pre-ect examination includes blood hematology and biochemistry as well as urine analysis, ECG, EEG, brain CT and examination by internist and anesthesiologist. At the day of treatment patient has to be NPO (no food or drink after midnight), and should empty his or her bladder before the treatment. A written informed consent and Ethics Committee approval is an obligatory part of ECT. 5 Treatment protocol. During the whole procedure, patient s vital signs, blood oxygenation saturation, cardiac rhythms (ECG), and electrical activity of the brain (EEG) are continuously monitored. In addition, electromyography (EMG) may be performed to evaluate the electrical activity of the muscles. EEG monitoring is crucial because it enables the practitioner to confirm that a cerebral seizure has occurred and has ended in a timely fashion. Anesthesia technique. Through intravenous line the patient receives general anesthesia. The induction agent of choice is methohexital. Other induction agents include propofol, thiopental, etomidate and ketamine. 5 Preoxygenation. The patient is preoxygenated with supplemental oxygen, with the goal of maintaining oxygen saturation near 100%. The patient is often hyperventilated immediately prior to delivering the electrical stimulus, because this induces cerebral hypocapnia, which increases seizure intensity. Anticholinergic medication. Premedication with glycopyrrolate or atropine is often used to prevent vagally-mediated bradycardia and excess oral and respiratory secretions. Muscle relaxation medication. Skeletal muscle relaxation is used during ECT to minimize the motor seizure and prevent musculoskeletal injury which is particularly important for patients with osteoporosis. The standard agent for muscle relaxation is succinylcholine. 5 Electrode placement. There are three typical ways of placing stimulating electrodes: bilateral, right unilateral and bifrontal. Bilateral or bifrontotemporal electrode placement. One electrode is placed on each temple, with the center of the each electrode approximately 2 to 3 cm above the midpoint of an imaginary line drawn from the tragus to the external canthus on each side of the head. This gold standard placement has the greatest antidepressant efficacy, but is also associated with more short-term and long-term cognitive side effects than right-unilateral ECT. Right unilateral electrode placement consists of placing one electrode on the right temple and one on the scalp, just to the right of the vertex. This technique avoids initial stimulation of the left cerebral hemisphere, which is usually dominant for language functions. This way of placing the electrodes may be slightly less effective for some patients, but generally causes fewer adverse cognitive effects. Thus, it is commonly indicated when there is a significant concern about minimizing retrograde amnesia. 195 april 2017 Gyrus Vol. 4 No. 2

3 Bifrontal electrode placement consists of placing each electrode on the forehead above the outer canthus of each eye. Cognitive impairment with bifrontal placement may be comparable to right unilateral. 5 Stimulus type. The type of stimulus used in ECT devices is a brief pulse (0.5 to 2.0 milliseconds) or ultra-brief pulse (<0.5 milliseconds) waveform. Brief pulse is considered standard due to its efficacy compared with ultra-brief pulse. The choice depends upon urgency of response, prior treatment history, and patient preferences. 5 Stimulus dose. The intensity of the electric stimulus affects efficacy, speed of response, and adverse cognitive effects. It is usually described in terms of seizure threshold, which is estimated empirically at the first treatment session. If the initial small dose does not produce a seizure, an incrementally higher dose is given until a seizure occurs, which then establishes the seizure threshold. The stimulus dose depends upon the electrode placement. The suggested stimulus dose for bilateral or bifrontal ECT is 1.5 to 2 times initial seizure threshold and the suggested dose for right unilateral is 6 to 8 times initial seizure threshold. 5 Seizure duration. Most therapeutic ECT seizures last 15 to 70 seconds on EEG recording. Seizures that are shorter than 15 seconds have a higher likelihood of being therapeutically ineffective, while prolonged seizures may be associated with increased cognitive impairment. A typical course of ECT consists of 6 to 12 treatments, individualized for each patient. 5 HYPOTHESES ON THE MECHANISM OF ECT S EFFECTS ON THE BRAIN Despite decades of research, the exact mechanism of ECT s effects on the brain is yet to be found. Recent theories have focused on the neurophysiologic changes produced by the ECT stimulus, which are likely related to ECT s anticonvulsant effects New research present that the magnitude of the change in seizure threshold over the ECT course is associated with therapeutic outcome, particularly with right unilateral (RUL) ECT. New findings also point out that the change in seizure threshold is inversely related to some inhibitory aspects of seizure expression, and is independent of the cumulative decrease in seizure duration. 6 Brain imaging (PET) has shown an increase in cerebral blood flow and cerebral metabolic rate during the ECT seizure and a decrease in cerebral blood flow and cerebral metabolism after the ECT seizure (postictal). Recently, a lot of attention was drawn to hippocampus (a structure in the limbic system which plays important roles in the consolidation of information from short-term memory to long-term memory and spatial navigation). 7 Research from 1965, published by Altman and Das, revealed that antidepressant treatments, particularly ECT, promote neurogenesis in the hippocampus, and that pathophysiologic reaction to environmental factors, such as stress, can reduce it. 7 The mechanism of action here may involve the up regulation of the expression of brain-derived neurotrophic factor (BDNF) in this region. Increased levels of stress-induced or exogenously-introduced glucocorticoids lower the expression of mrna for BDNF in the adult rat hippocampus; ECS have been shown to block the stress-induced down regulation of BDNF ECT acutely elevates certain hormone levels such as prolactin, TSH, oxytocin, vasopressin, and glucocorticoids, which may or may not be connected to antidepressant effect of the ECT. Different effects have been reported, indicating both way of stimulus administration, and placement of electrodes modulate the final result of the treatment. ECT was initially delivered using a sinusoidal waveform, which proved to have had more cognitive side-effects. Instead, the brief pulse stimulus, widely used today, reduces chance of memory loss as a side-effect. 7 INDICATIONS ECT is primarily given for treatment-refractory, severe clinical presentations. Most frequent indication for ECT are mood disorders, major depressive disorder (MDD) being the commonest, which encompasses more than 80% of all cases. Unipolar depression, after up to 8 treatments has shown high remission rates of 75% or even higher. Unchanging abnormal mood, vegetative signs, delusional thoughts, and psychomotor retardation or agitation, are predictors of good outcomes with ECT. Bipolar disorder (BD), current episode depressed is another indication, which responds to ECT therapy almost as good as unipolar depression. Depressive Mood Disorders with Psychosis. In patients suffering from depressive disorder with psychotic features, even higher remission rates can be achieved (almost 90%), compared with nonpsychotic patients. Suicide Risk. The presence of suicidal thoughts and acts is another major reason to consider ECT earlier in the treatment course, as a rapid reduction in expressed suicidal intent can be expected in just few weeks of therapy. 7 Bipolar disorder (BD), current episode manic ECT is generally used in patients who are intolerant of, or refractory to, lithium and other antimanic agents. However, ECT shouldn t be taken into account as a last resort treatment in bipolar disorder (BD). In severe cases where the patient is at significant risk of harming self or others, requiring physical restraint or large doses of sedatives, or when the symptoms are life-threatening owing to exhaustion, ECT should be considered earlier. Catatonia. The most dramatic improvement with ECT is encountered in patients presenting with catatonia, regardless of the underlying condition. These patients present with stupor, mutism, refusal to eat or drink, excitement or hypokinesis, or repetitive movements. They hold abnormal rigid body positions, and show motor and other behavioral resistance to following simple requests or commands. Considering its benefits in these acute states, ECT should be used here as a first-line treatment

4 Malignant catatonia is a syndrome of acute onset, fever, and autonomic instability of life-threatening dimensions. Benzodiazepines are the treatment of first choice in catatonia, with reported remission rates of 80% or higher within days. Should initial treatment with benzodiazepines fail, ECT is to be used without delay. 8 CONTRAINDICATIONS AND RISKS Induced seizure causes transient increases in blood pressure, pulse and intracranial pressure. These changes might have deleterious effects on certain patients. Organ systems of most concern are cardiovascular, pulmonary and central nervous system. 8 Absolute contraindications. ECT has no absolute contraindications. Relative contraindications. The most significant relative medical contraindications to ECT are mostly associated with serious unstable cardiovascular disorders and CNS disorders, such as acute myocardial infarction, serious arrhythmias, uncompensated congestive heart failure, aortic and cerebral aneurysms, brain tumors, cerebral hemorrhage and any other state that can cause increased intracranial pressure. However, these risks can usually be modified pharmacologically. 8 Pregnancy. ECT is not contraindicated in pregnant patients, however, there are some modifications in ECT technique. Pacemakers and cardioverter defibrillators. With a proper pre-ect evaluation, patients with cardiac pacemakers and implantable cardioverter defibrillators can safely undergo ECT. ECT is one of the safest procedures performed under general anesthesia. It is generally estimated that mortality rate is comparable to that for anesthesia alone. Deaths are mostly related to cardiac complications. 8 SIDE EFFECTS General (somatic) medical effects. The most common immediate unpleasant effects of ECT are headache, nausea and vomiting. Loss of appetite and functional bowel disorders are slightly less frequent. 1 Headache is present in almost half of the patients, and usually responds to common analgesics. Nausea is the result of anesthesia and airway manipulation, which may introduce air into the stomach. In patients with significant post-ect nausea, prophylactic treatment with agents such as ondansetron may be used. Other less common somatic side effects include myalgias, aspiration pneumonia, fractures (that may occur in patients with severe osteoporosis), dental and tongue injuries. 1 Cognitive side effects. Three basic types of transient cognitive impairment are acute confusional state, anterograde amnesia and retrograde amnesia. Its incidence, duration and severity depend on electrode placement (more prominent in bilateral than in unilateral ECT), stimulus type and dose (more prominent in high-dose than the lower dose ECT), anesthesia, and the patient s pretreatment cognitive status (older patients usually have more prolonged and more severe periods of confusion). 8 An acute confusional state, which is a result of both the seizure and the anesthetic administration, typically resolves 10 to 30 minutes after the procedure. Anterograde amnesia is the impairment in retaining newly acquired information. It typically resolves within two weeks after completing the course. Retrograde amnesia refers to the inability to recall memories for events occurring before and during the course of ECT, wherein impersonal memory is affected more significantly than personal memory. Retrograde amnesia recovers more slowly than anterograde amnesia. Some amnesia may be permanent. However, objective tests indicate that cognitive abnormalities caused by ECT are generally short lived. Nevertheless, modified ECT techniques, substantially reduce the risk of serious cognitive side effects. 8 CONCLUSION Although ECT is highly effective and superior to other therapies in certain psychiatric conditions, it is still not widely used. In fact, it is often perceived as a last resort, since its side effects, such as memory loss seem frightening, and the benefits are often overlooked. In addition, the public, as well as some medical professionals, still lack information about the current practice of ECT, which is very different from images and records of early ECT treatment, often depicted in films and literature. The fact that ECT is recommended to treat potentially life-threatening conditions cannot be overstated. Thus it is of huge importance that medical community become more actively engaged in fighting stigma of ECT, by providing thorough and specific information to 1,4, 5,7 patients, their families, the press and other media. There is only one calamity: ignorance. And there is only one solution: enlightenment. Jaggi Vasudev 197 april 2017 Gyrus Vol. 4 No. 2

5 References: Payne NA, Prudic J. Electroconvulsive Therapy : Part I. A Perspective on the Evolution and Current Practice of ECT. Journal of psychiatric practice. 2009;15(5): Greenberg RM, Kellner CH. Electroconvulsive Therapy: A Selected Review. Am J Geriatr Psychiatry. 2005;13(4): Overview of electroconvulsive therapy (ECT) for adults. Accessed: 29 June 2017 Payne NA, Prudic J. Electroconvulsive Therapy: Part II. Journal of psychiatric practice. A Biopsychosocial Perspective. 2009;15(5): Technique for performing electroconvulsive therapy (ECT) in adults. Accessed: 29 June 2017 Sackeim HA. The anticonvulsant hypothesis of the mechanisms of action of ECT: current status. The journal of ECT. 1999; 15(1):5-26. Baghai TC, Moller H. Electroconvulsive therapy and its different indications. Dialogues in clinical neuroscience. 2008: Pascal S. What We Have Learned About Electroconvulsive Therapy and Its Relevance for the Practising Psychiatrist. The Canadian Journal of Psychiatry. 2011;56(1):5-12. Elektrokonvulzivna terapija (EKT) u modernoj psihijatriji Sažetak Elektrokonvulzivna terapija primjer je nefarmakološke terapije koja se koristi u liječenju određenih psihičkih poremećaja. Danas se najčešće upotrebljava za liječenje teških depresivnih epizoda, ali je indicirana i za psihotične pacijente, katatone poremećaje, maniju, bipolarni poremećaj, neuroleptični maligni poremećaj i druge. Tijekom primjene EKT-a, mala količina električne struje pušta se kroz mozak uzrokujući kemijske promjene. Sigurnost EKT-a poboljšana je korištenjem modificiranih stimulirajućih tehnika i napretkom u moderne anestezije. S obzirom na visoku učinkovitost, nuspojave poput konfuzije, mučnine i kratkoročnog gubitka memorije, praktički su zanemarive. Unatoč svemu navedenome, EKT je i dalje stigmatizirana terapija, ne samo u psihijatriji, već i u cijeloj medicini. Ključne riječi: BDNF, elektrokonvulzivna terapija, poremećaji raspoloženja, psihijatrija Received November 14, Accepted April 11,