Clinical Practice Guidelines for the Use of Electroconvulsive Therapy.

Abstract

INTRODUCTION Electroconvulsive therapy (ECT) is a clinical procedure where a small dose of electric current is passed through the brain for a brief period to induce seizures for therapeutic purposes in psychiatric (and certain neurological) conditions. Modified ECT is the modern form of ECT where the electrical stimulus is given under general anesthesia and muscle relaxation. This is one of the most effective treatments for many psychiatric conditions. Modern modified ECT is a safe treatment when practiced with adequate knowledge, skills, and expertise. Following the basic standards of ECT practice is necessary for better clinical outcomes including minimal cognitive adversities. This guideline document is aimed at enabling consistent, safe, and effective practice of ECT in patients in applicable psychiatric disorders. METHODS These guidelines are developed as part of the initiative of Clinical Practice Guidelines (CPG) subcommittee of Indian Psychiatric Society. The initial draft guideline was developed by the authors. The information was sourced from key research articles, national/international guidelines on psychiatric care, and ECT. No formal systematic literature search was conducted. The current guideline was prepared to suit the existing Indian mental health care system and legislations. The draft was further presented and discussed in the in-person workshop of CPG-2022. The draft was revised following the discussion in the workshop based on the consensus-based recommendation method. This guideline is not a directive or mandatory instruction but a guidance document for professional practitioners administering ECT. This is not a full and complete review of ECT procedure. But it is intended to improve patient outcomes by facilitating best practice standards by maximizing benefits and minimizing adversities. USE OF ELECTROCONVULSIVE THERAPY Indications Table 1 shows the indications for ECT. Evidence exists for the efficacy of ECT in depressive episodes, manic episodes, and acute exacerbations of psychosis in schizophrenia. Treatment-resistant depression, mania, and schizophrenia, including clozapine-resistant schizophrenia, are well-recognized indications,[1-6] with evidence from comparative trials (comparison across types of ECT or with waitlisted patients). ECT should not be withheld until the failure of several medication/psychotherapy trials in severe depression. Health economics suggest that it is beneficial to consider ECT as a second or third line agent in severe depression. ECT is considered as first-line (primary) treatment for emergency psychiatric conditions across diagnoses. These include high suicidality, catatonia, excitement, aggression, poor oral intake, acute psychotic symptom exacerbations, and severe physical debilitation secondary to psychiatric disorders.[7-13] The rigor of the evidence base is limited for such indications due to ethical and pragmatic considerations in conducting sham-controlled trials in these emergency life-threatening transdiagnostic situations. It may be noted that almost all international standard guidelines suggest ECT as a first-line treatment option for these indications.[8-13]Table 1: Indications of ECTPredictors of response In general, older age, psychotic symptoms, and shorter episode duration are predictors of response to ECT. Melancholic features and greater baseline depressive symptom severity are also associated with better ECT response. Past good response to ECT is considered a good predictor of response for the current episode. Continuation/Maintenance (C/M) ECT should be considered for patients with a history of severe, recurrent episodes who have failed to remain well on medications.[14] ECT is a first-line treatment when rapid and/or definitive response to avert harm to self/others is needed. Acute suicidal risk, agitation, catatonia, and deteriorating physical status secondary to psychiatric conditions are some of such situations. After an acute course of ECT, C/M treatment with pharmacotherapy and/or psychotherapy is needed. All the indications mentioned above have to be individualized and should be based on the clinical needs, patient’s preferences, and putative risk of adverse effects. ECT staffing ECT without anesthesia and muscle relaxation is now prohibited under the Mental Health Care Act, 2017. Hence, the staffing shown in Table 2 is advisable for administering modified ECT.Table 2: Staffing for ECTTreatment site and equipment The treatment suite ideally involves three distinct areas, but which are nearby or closely connected:[9,10] a. Waiting/preparation room: should have the following facilities: i. Waiting area for patients and caregivers ii. Space for assessment: for interviewing, examining, verifying the records, and to ensure adequate preparation iii. Sphygmomanometer and stethoscope b. ECT administration room i. ECT apparatus including bite block, electroencephalogram (EEG) monitor, and ECG monitor ii. Anesthetic agents (e.g., thiopentone, propofol, etomidate, ketamine, isoflurane, sevoflurane, etc.) and muscle relaxants (along with succinylcholine, at least one nondepolarizing agent like atracurium or rocuronium should be available) iii. Emergency medication tray to manage uncontrolled hypertension, hypotension, cardiac arrhythmia, cardiopulmonary arrest, anaphylactic shock, prolonged seizure, and status epilepticus. This should include intravenous fluids, epinephrine, dopamine, atropine or glycopyrrolate, cholinesterase inhibitors (neostigmine, physostigmine), anticonvulsants (lorazepam, diazepam, phenytoin), steroids, beta blockers (esmolol, labetalol), alpha-blockers (prazosin, clonidine), vasodilators (nitroglycerin, hydralazine), antiarrhythmics (lidocaine), analgesics (paracetamol), antiemetics (domperidone, metoclopramide), antihistamines (chlorpheniramine, cetirizine), bronchodilators (aminophylline) among others) iv. Vitals monitoring: sphygmomanometer, reflex hammer, oxygen saturation, ECG v. Intubation set: oral and naso-pharyngeal airways vi. Oxygen delivery system with intermittent positive pressure ventilation capabilities through a mask as well as endotracheal tubes vii. Suction apparatus, iv infusion set, syringes with needles, cotton and gauze pads, hand gloves. viii. Defibrillator ix. Portable cots/beds, disposable containers c. Recovery room: should have all items iii to ix listed above Informed consent (Supplements 1–4) Written informed consent has to be taken before initiating ECT based on principles of shared decision-making. Consent should be taken following due procedures in accordance with the highest ethical standards and applicable laws/regulations. Written information material may be provided to the patient and caregivers, and adequate time should be provided for reverting with any clarifications. Information should be provided regarding the anticipated benefits and possible short-term and long-term adverse effects of modified ECT, including possible risks with both anesthesia and ECT, in the given individual. Discussion on the type of ECT, modification procedure, electrode placement, and expected outcomes should be included in this process. Unless the patient disagrees, it is recommended to make caregivers a part of the consenting process. If a patient does not have the capacity to consent, the same needs to be documented. The advance directives, if any, have to be examined and, in accordance with that, consent may be obtained from the nominated representative. In the case of minors, oral/verbal assent (as per the age) should be obtained along with written informed consent from parents/nominated representative; the decision about initiating ECT has to be taken only after concurrence by two independent psychiatrists or a psychiatrist + a physician, and due permission from the mental health review board as per the law. As and when a patient regains the capacity to consent or attains 18 years of age, his/her consent has to be obtained for continuing ECT sessions then onwards.[15,16] Consent has to be obtained again before initiating C/M ECT, as the clinical condition, purpose (consolidation/relapse prevention), and character of treatment (frequency of ECT sessions and end-point) would have changed. Pre-ECT evaluation (Supplement 5): This should be performed as close to the ECT course as possible. Psychiatric and physical evaluation Psychiatric evaluation is needed to ascertain indications. Rating scales can be used to determine these indications systematically and measure the changes during the ECT course. If the patient has received ECT in the past, details of the electrode placement and electrical parameters in earlier ECTs, level of achieved response, and associated cognitive deficits would guide the current course of ECT. It is important to evaluate the psychotropic medications that can potentially interfere with anesthesia and ECT. For instance, anticonvulsants increase seizure threshold; antipsychotics like chlorpromazine and clozapine are known to be pro-convulsants; lithium can increase the risk of postictal delirium; tricyclic antidepressants are known to increase the risk of cardiac adverse events during ECT/anesthesia. Physical examination is needed to identify any relative contra-indications and prevent complications [Table 3]. It should mandatorily involve fundoscopic examination along with other systemic examinations. Dental evaluation for loose or missing teeth, cardiovascular examination for arrhythmias, assessment for neurological comorbidities, and pulmonary clinical evaluation are mandatory.Table 3: Clinical conditions requiring caution while administering ECTPreanesthetic evaluation is recommended to plan for an anesthetic agent and a muscle relaxant. Also, suitable investigations or interventions can be planned in the presence of medical conditions associated with a substantial risk for general anesthesia-related complications. Liaison with other specialist physicians if deemed is necessary by the psychiatrist/anesthetist. Baseline cognitive screen Monitoring of cognitive adverse effects would be necessary for patients receiving ECT. Baseline knowledge of cognitive abilities is crucial in attributing the changes in cognitive abilities with ECT. Hindi Mental Status Examination and Mini Mental Status Examination are simple tools for monitoring, but are not sensitive to subtle cognitive changes associated with ECT. Montreal cognitive assessment battery (MoCA) and brief ECT cognitive screen are assessment tools used internationally. “Battery for ECT-Related Cognitive Deficits” (B4ECT RECODE) is a tool validated in the Indian population and is recommended to be used during the initiation and course of ECT.[10] Investigations For general anesthesia: hemoglobin levels, blood sugar, electrolytes, blood urea, and serum creatinine would facilitate the detection of common risk-enhancing medical comorbidities but are not mandatory. Similarly, X-ray, electrocardiography, echocardiogram, and other tests would be indicated based on physical evaluation and associated medical comorbidities TREATMENT PROCEDURE ECT is mandatorily used as a modified procedure, as per the law in India. The modification involves using muscle relaxants to reduce the neuromuscular injuries and using anesthetic agents to induce sedation and amnesia for the procedure involving muscle relaxation and electrical stimulation. a. Anesthesia Preparation before anesthesia [Figure 1, Table 4 and Supplement 6]The procedure may be anxiety provoking. So, reassure patients while initiating the procedure including while securing iv access and placing the mask for oxygenation.An ideal anesthetic agent for ECT would be rapidly inducing and short acting (early emergence from effects of anesthesia), has a good amnesic effect and stable systemic/cerebral hemodynamics during ECT, and would not have any effects on seizure threshold. Tables 5 and 6 provide information helpful in selecting anesthetic agents.[17]A combination of propofol and ketamine called ketofol can be used to balance seizure duration and hemodynamic effects. Adjunctive short-acting opiates (remifentanyl, alfentanil, fentanyl) or dexmedetomidine have dose-sparing effects and can be used, but they need more evidence of their exact role in ECT. The differential effects of anesthetic agents are dependent on their dose, and this needs to be considered while choosing the anesthetic agent.Muscle relaxation is an important component of modified ECT. Ideal muscle relaxants should have the ability to avoid musculoskeletal injury without affecting cerebral seizure activity and provide rapid recovery without residual paralysis. Succinylcholine (0.3–1 mg/kg) is a preferred muscle relaxant due to its rapid onset and recovery. Nondepolarizing muscle relaxants may be considered in certain conditions. These include peudocholinesterase deficiency, recent organophosphorus poisoning, severe, widespread burns, hypercalcemia, severe neuromuscular disease or injury (e.g., quadriplegia, amyotrophic lateral sclerosis, muscular dystrophy), history of malignant hyperthermia in the patient or his/her family. In a patient with suspected/known history of a recent (4 weeks) suicide attempt and referred to ECT, a high suspicion of organophosphorous poisoning should be considered. There are reports of prolonged apnea even after 4 weeks of poisoning. Clinicians may consider the assessment of pseudocholinesterase level when in doubt or may use of nondepolarizing agents in such cases.Pseudocholinesterase level can be assessed in patients with high suspicion (e.g., patients belonging to Arya Vysya community, an earlier history of prolonged apnea). Routine determination of pseudocholinesterase level is not recommended. Routine prophylactic use of anticholinergics (atropine/glycopyrrolate), beta-blockers, calcium channel blockers, nitrates, hydralazine, and ganglionic blockers for cardiovascular stability is not recommended. Wherever used, the rationale for using such an agent should be noted. b. ECT Dosing The protocol of ECT varies considerably and choice on the protocols should be based on individual needs of a given patient. The rapidity of needed response, effectiveness, and potential cognitive adverse effects of the protocols should guide the choice. Rather than any set of protocols, it is important to have knowledge of each parameter in the protocol, and personalization of protocol can be done based on clinical situations.[18,19] i. Electrical Parameters A brief or ultrabrief pulse is strongly recommended and should be administered with a constant current device. Sinewave ECT and constant voltage systems are not recommended in the modern practice of ECT due to safety concerns. Electrical charge is generally considered as a linear measure and chief parameter of dosing. But this approach is faulty, and the combination of electric current intensity, pulse width, pulse frequency and train duration (number of pulses) along with electrode placement (stimulation site), frequency of sessions and duration of session should be carefully considered in choosing a protocol. Electrical current intensity: Historically, 500–1000 mA has been used in the practice of ECT. Most devices come with a default current of 800–900 mA. The current intensity is known to linearly correlate with tolerability, cognitive as well as seizure quality but is generally kept constant and not modified during dose incrementation. Recently, low amplitude (200–400 mA) has been explored as part of individualized low-amplitude seizure therapy.[20] Its clinical utility is yet to be understood. Pulse width: ECT is classified as brief pulse (0.5–2 ms) and ultrabrief pulse (0.2–0.4 ms). Pulse width is likely to have a linear effect on cognitive adverse effects with broader widths being associated with worse cognitive effects. Ultrabrief pulse of 0.3 ms has been shown to have a cognitive advantage over brief pulses with right unilateral placement in depressive disorders. But the antidepressant efficacy may be compromised with it. A lower range of brief pulse (0.5–1 ms) may be considered optimal to obtain a rapid clinical effect. But when cognitive effects are of major concern, a stimulus with ultra-brief pulse width may be chosen.[21] Pulse frequency: The number of biphasic pulses every second is the electrical parameter that is inverse of the interpulse interval. It is an important electrical parameter that generally ranges from 20 to 240 pulses/s (10–120 Hz, i.e., bidirectional pulse pair per second). Stimuli with lower frequencies are generally more efficient, i.e., a seizure can be elicited at a lesser charge with lower frequency than with higher frequency when all other parameters are kept constant. Many ECT devices in the default increment method involve an increase in frequency. ECT clinicians should be aware of this aspect while using a default way of increasing stimulus charges to address the issue of high seizure threshold. Train duration: This is the most commonly modified parameter to set the dose. Generally, the pulse duration is limited by the devices. Most devices have a range of 0.2–8 s, but certain devices come with the highest limit of up to 16 s. No limit has been examined/recommended on the highest duration. An increase in charge is achieved by increasing train duration till the upper limit of the device is reached. The number of pulses: It is directly a factor of train duration and will also be influenced by pulse frequency. The number of pulses may intuitively suggest a direct correlation with seizure. But as “crowding of pulses” is inefficient in eliciting seizure, the number of pulses by itself may not be a good indicator for setting electrical parameters. Directionality: The default ECT parameter widely applied is bidirectional current. There are preliminary trials of unidirectional current – anodal at one site and cathodal at the other. But the evidence is limited to suggest the clinical utility of unidirectional current. Patterned doses: Bursts of pulses are provided similar to theta bursts in transcranial magnetic stimulation. The available evidence is for continuous pulses with similar intervals, which is supported by most commercially available devices. Currently, patterned pulses cannot be recommended for routine clinical application. ii. Electrode placement The electrodes are placed in different ways [Figure 2]:[22-25] 1. Bilateral: Bitemporal: Classical method. One electrode is placed in the frontotemporal region (one inch above the imaginary line joining the outer canthus and external auditory meatus). Bifrontal: Electrodes placed on frontal regions (2 inches above outer canthus on an imaginary vertical line perpendicular to the imaginary line joining two pupils). Clinical trials have shown that bifrontal is equally if not more effective than bitemporal placement, but with lesser cognitive effects in patients with mania, depression as well as schizophrenia. Left anterior right temporal: Asymmetrical placement of electrodes with the left side on the frontal region and right on frontotemporal regions is reported. Evidence from systematic studies is lacking for this placement. 2. Unilateral: Right unilateral: One electrode is placed on the right frontotemporal region and another electrode 1 inch right to vertex (point of crossing of two imaginary lines, one joining two tragi and other joining nasion-inion). This is shown to have lesser cognitive adversities but requires nearly 4–6 times the threshold dose when provided as an ultrabrief pulse for efficacy, equaling that of bilateral placements. Left unilateral: Same as right unilateral on the left hemisphere. This is found to be equi-efficacious to the right unilateral. This placement can be chosen when sparing nonverbal and visual memory is needed more than sparing verbal memory. It is also considered in those having the right dominant brain function. The evidence for the efficacy of unilateral ECT is available only for depression. The evidence of unilateral ECT is lacking for other common indications (namely, schizophrenia or mania). iii. Dose of ECT ECT dosing is discussed in terms of charge (milliCoulombs, mC). A higher charge is associated with better efficacy and higher cognitive adverse effects. But as discussed earlier, the charge is not a linear measure but a combination of multiple electrical parameters [Figure 3]. Table 4: Preparation for ECT procedureTable 5: Summary of critical properties of anesthesia agents in choosing for ECTTable 6: Dosage and selected properties of anesthetic agents used during ECTFigure 1: Steps of preanesthesia preparationFigure 2: ECT electrode placementsFigure 3: Electrical parametersElectrical charge = Current intensity × pulse width × pulse frequency × train duration. The total dose for optimal efficacy through repeated ECT sessions is considered with respect to the seizure threshold; efficacy is also dependent on pulse width and electrode placement. Marginally suprathreshold charge (1.5 × seizure threshold) is recommended in bilateral (Bitemporal/Bifrontal) ECT with brief pulse ECT (pulse width of 1 ms or more). Some evidence suggests a requirement of a higher charge (2.5 × seizure threshold) when a lower range of brief-pulse (0.5 ms) is used with bilateral ECT. There is strong evidence that a markedly suprathreshold (6 × seizure threshold) is required with ultrabrief (0.3 ms) ECT, with the evidence available for primarily right unilateral ECT, specifically in depression. For right unilateral ECT with brief pulse width, electrical charge is to be considered 4–6 times the seizure threshold. Ultrabrief bilateral (bifrontal/bitemporal at 0.3 ms) is found to be less effective and may not be advisable with the existing evidence. Ideally, the dose increment has to happen for a fixed current amplitude, pulse frequency, and pulse width. Hence, the suprathreshold dose should also be a function of train duration. But most of the standard devices have a limitation of train duration at 4–8 s in default settings, and they increase pulse frequency to increase the total duration. Most studies have used these default increments, and hence this guideline should be read with caution. More studies are needed to ascertain this need. Dose estimation methods:[26,27] Stimulus titration method: This will be the recommended method in regular practice. The first session can be spared in finding the lowest dose needed for seizure threshold estimation. Formula-based methods can be used as guidance for identifying the first dose of titration. Faster titration may be attempted with higher increments between stimuli in elderly patients, and slower titration with smaller increments may be attempted in adolescents/younger adult patients. Subsequent sessions can be provided at suprathreshold doses as discussed above. Formula-based methods: Based on the age and sex of the patient, different formulae are derived. There is a need to be cautious in using the formula, as medications and anesthetic agents may impact the seizure threshold. The stimulus should have the same amplitude, pulse width, pulse frequency, and electrode location from which the formula was derived. Fixed high dosing: This uses a single high dose, commonly the maximum for all the sessions. The use of a high fixed dosing strategy should be reserved only for patients with sufficiently serious concomitant medical conditions in which avoidance of subconvulsive stimulation is a priority Dosing from benchmark: A high dose will be administered at the first session. The peak heart rate and tonic-clonic convulsions would be observed. In subsequent sessions, the doses are down-titrated to continue at the lowest dose producing a similar outcome. This could be a better alternative to the continued fixed high dosing method, wherever it is used. c. Procedure and monitoring [Supplements 7 and 8] i. ECT procedure [Figure 4] Figure 4: Steps of ECT procedureSeizure monitoring Hamilton cuff method is recommended for monitoring motor seizures by isolating the ipsilateral limb (right limb in the right unilateral ECT) from muscle relaxants. EEG gives a direct measure of seizure activity and is recommended wherever available. Bilateral EEG recording from at least two channels (FP1 and FP2) referenced to the ipsilateral mastoid is preferred. When only a single channel is available, a contralateral channel is preferred. EEG recording can have artifacts due to muscle movements and other technical issues. Hence, motor monitoring should always be used to supplement EEG. Adequate seizure Good quality seizure should be given more importance than any specific duration. A good quality seizure, even of shorter duration, has been demonstrated to be efficacious in elderly depressed patients. Earlier definition of 15 s of motor seizure and 25 s of EEG seizure to define adequate seizure is found to be of little clinical or prognostic benefit. Good quality motor seizure involves different stages. Initially, there is a gradual seizure induction during (or soon after the end of) the stimulation. This will be followed by tonic contraction. Bilateral convulsions will emerge, which will end gradually. A comatose stage will succeed the convulsions, with the gradual regaining of consciousness and orientation. The motor manifestation should be monitored even in the presence of EEG monitoring. Hamilton cuff method of isolation and monitoring of the convulsion in the ipsilateral limb (in case of unilateral electrode placements) is preferred in modified ECTs, as it indicates generalization of seizures. Time from the beginning of ECT stimulus till the end of the last clonus in any part of the body (usually ends in the limbs) shall be considered for motor seizure duration. Good quality EEG seizure involves the visualization of seizure activity in contralateral channels. Good quality EEG seizure will have four phases [Figure 5]: Phase 1: Recruitment stage involving high-frequency waves with gradually increasing amplitude. Phase 2: Hypersynchronous high amplitude polyspike bursts at around 10 Hz lasting 10–20 s corresponds to tonic contraction. Phase 3: Hypersynchronous polyspikes intermixed with slow waves for 20–40 s correspond to the tonic-clonic phase. Phase 4: Postictal suppression – a flat isoelectric line is seen. The onset of this phase heralds the end of seizures. Phase 5: The last phase is recovery from delta to theta to alpha waveform. Visualization of EEG is better in younger patients than in elderly patients. Figure 5: Phases of electroconvulsive therapy-induced electroencephalogram-monitored seizuresMissed seizure: If there is no motor or EEG seizure even after 20 s of completion of electrical stimuli administration, then restimulation may be attempted by increasing the stimulus dose. Delayed onset seizure should be watched out for. Inadequate seizure: If the EEG seizure is of low quality or the motor seizure is nongeneralized, limiting to one side of the body or restricted to the facial region only, restimulation at higher doses may be attempted after 45 s. Restimulation may be attempted till the patient comes out of anesthesia/muscle relaxant. Generally, four to five restimulations can be attempted. If needed, reinduction of anesthesia, or “top-up” dose, can be requested from the anesthetist. It may be noted that top-up doses reduce the quality of seizures. If the seizures are very brief (e.g., 5–10 s duration), and if the patient is showing the expected clinical response, then restimulation with a higher dose need not be administered. Restimulation on the same day after adequate seizure, called the multiple monitored ECT (MMECT), is not recommended. Even in cases of unilateral ECT, markedly suprathreshold stimulation would not be necessary on the first day of titration. This might be considered only extremely rare life-saving conditions like neuroleptic malignant syndrome or intractable seizures. In the case of a prolonged seizure (seizure longer than 180 s), termination can be attempted if a seizure extends beyond 120 s. Airway and respiration should be closely monitored till the complete cessation of seizure. A seizure may be terminated using benzodiazepines, phenytoin, valproate, or barbiturate (usually, the anesthetic agent used for induction). If the patient is on theophylline or lithium, stopping them temporarily or alternatives may be considered. Shifting to anticonvulsant anesthetic agents may also be considered. Left lateral positioning and monitoring in the ECT suite should continue under the care of an anesthetist till spontaneous breathing is gained. Then, the patient can be shifted to the recovery room. ii. Monitoring in the recovery room Monitoring of the vitals should be continued: pulse rate, blood pressure, and oxygen saturation. ECG should be monitored in high-risk patients (history of cardiac disease). Patient should be monitored for agitation/delirium, aspiration, arrhythmia, tardive seizure, enuresis/encoperesis, and neuroleptic syndrome. Feeding should be avoided until the patient regains full consciousness. Any adversities during the procedure should be evaluated for: tongue bite/mucosal injury, musculoskeletal injuries (fractures, dislocations). Orientation and gait should be assessed for recovery to baseline or near baseline before shifting the patient from the recovery room. iii. During the course of ECT treatment. The number of ECTs should not be predetermined but should be based on the needs of individual patients. Progress in terms of clinical symptoms and cognitive and other adverse effects should be monitored at least once a week during the course of ECT. ECT may be terminated at any time if complete clinical improvement/remission is achieved. If satisfactory clinical improvement is not observed, a minimum of 8–12 ECT sessions should be provided in acute courses before considering