The first use electroconvulsive therapy (ECT) occurred in 1938 to treat a patient who suffered from a psychotic illness.1 Introduced at a time when few treatments for severe psychiatric illness existed, the use of ECT spread quickly and its benefits in treating other neuropsychiatric conditions rapidly became recognized.2 Although depressive disorders have evolved into the most common indication for ECT use in the United States, Australia, New Zealand, and some European nations,3 this is not necessarily true worldwide. Schizophrenia, in particular, is a common indication for ECT in Asia, Latin America, Africa, and Russia.4 Although the safety and effectiveness of ECT in numerous conditions have been well established through decades of clinical experience, earlier studies may not have met current scientific standards, thus leaving regulatory agencies and device manufacturers in limbo—unwilling to “reinvent the wheel” by commissioning large-scale studies to confirm what is already generally accepted, yet unable because of administrative requirements to fully accept existing data.2,4
The US Food and Drug Administration (FDA) categorizes medical devices based on safety and effectiveness data. Class I devices are considered to have the lowest risk, and Class III are considered as the highest. ECT devices are “preamendment devices” (ie, introduced prior to the passage of the Medical Device Amendments to the Federal Food, Drug and Cosmetic Act), and as such they were automatically assigned to Class III; however, in December 2018, the FDA reclassified ECT devices to Class II for the treatment of catatonia or major depressive episodes (MDEs) associated with either unipolar major depression or bipolar disorders in patients older than age 13 years with severe, treatment-resistant forms of MDEs or in need of rapid response due to severe manifestations of illness.5 The FDA noted that there was sufficient information available to mitigate known risks of the devices and that a “reasonable assurance of safety and effectiveness” existed for their use. However, the FDA concluded that this level of evidence does not yet exist for other indications (eg, schizophrenia, schizophreniform disorder, schizoaffective disorder, bipolar manic and mixed states); so for these indications, ECT devices remain in a more restrictive category (Class III). Manufacturers are restricted in their advertising of how and what their product can do,5 but because the FDA does not dictate physician practice, the ECT provider can still use his or her professional judgment and provide ECT for other conditions,4 similar to the practice of prescribing medications “off-label.”
First-line treatment for severe forms of mania and mixed phases of bipolar disorder generally is considered to be a combination of an antipsychotic and a mood stabilizer.6 Although highly effective in all phases of bipolar illness, ECT is usually offered only to those patients who have proven resistant to pharmacotherapy (ie, those who have failed to respond to a combination of two or more antipsychotics and mood stabilizers for 16 weeks).7 Although clozapine is used in patients who are not responsive to the combination of first-line antipsychotics and mood stabilizers, it is unclear how clozapine fits into the above definition, as clozapine appears to be superior to other antipsychotics in treatment of mania and mixed episodes.8
Thus, use of ECT in mania is generally reserved for situations in which there is need for immediate clinical response due to associated suicidality and/or severe and sustained agitation or aggression. Previous history of positive response to ECT and patient's preference should be taken into consideration. Of note, ECT is especially effective when bipolar disorder is associated with catatonic states, with reported response of 80%, and hence should be the treatment of choice in such clinical situations.9
Maintenance of remitted or clinically improved state in bipolar disorder is a well-known clinical challenge, especially in the rapid cycling type of bipolar disorder. No randomized controlled trials (RCTs) have examined the efficacy of continuation or maintenance ECT in bipolar disorder, but two naturalistic observation studies support the use of continuation or maintenance ECT in bipolar disorder by reducing hospital readmission rate and hospital length of stay.10,11 In a case series of 14 participants, Minnai et al.11 found that monthly maintenance ECT in patients with severe rapid cycling illness reduced illness duration 13-fold (from 304 to 25 days per year), and increased illness-free intervals 6-fold (from 52 to 334 days per year).
A recent international survey of professional organizations with published guidelines for the treatment of mania showed that 7 of 9 organizations listed ECT as an option for the second-line treatment of mania.12 A review that included 50 years of research on ECT in the treatment of mania concluded that 80% of people with mania showed clinical improvement when treated with ECT, and that ECT is an effective treatment option in patients with poor response to pharmacotherapy.13
Bitemporal electrode placement appears to be more effective than right unilateral placement.14 A study by Hiremani et al.15 reported that patients with mania randomized to bi-frontal ECT responded faster than those randomized to bitemporal ECT, although outcome (including cognitive side effects) were comparable in both groups. Similarly, a study by Barekatain et al.16 concluded that moderate-dose bifrontal and low-dose bitemporal ECT had comparable efficacy, with bifrontal ECT having fewer cognitive side effects. A study by Mohan et al.17 compared twice-weekly bitemporal ECT dose delivered at seizure threshold versus at 2.5 times the threshold to treat mania and found no difference in efficacy.
A study by Sikdar et al.18 compared ECT versus sham ECT plus chlorpromazine for treatment of mania and found that 12 of 15 patients who received ECT responded, as compared to only 1 of 15 patients in the sham-ECT/chlorpromazine group. It should be noted, however, that reported efficacy of antipsychotics is typically higher than what was found in this study, possibly because treatment occurred only over a period of approximately 2 weeks, so it is likely that more participants would have responded to chlorpromazine given a longer period of treatment. However, this highlights the rapidity of ECT response as compared to pharmacotherapy alone.18,19 All these trials found that ECT was efficacious in mania, with response rates ranging from 70% to 80%.14–17,20
Three organizations (The British Association of Psychopharmacology,21 The Royal Australian and New Zealand College of Psychiatrists,22 and The World Federation of Societies of Biological Psychiatry23) recognize ECT as an effective treatment for bipolar disorder mixed episodes. Studies specifically addressing bipolar mixed states are limited and there are no randomized controlled trials demonstrating efficacy. However, numerous case series, retrospective studies, and naturalistic studies have demonstrated efficacy of ECT in mixed states.7,9,24
There is evidence to suggest that people with mixed bipolar states respond as well to ECT as those in manic or depressive episodes, although they may need more treatments.24 Conversely, other researchers have found that response rate in mixed episode bipolar disorder may be greater than in bipolar depression, and in one group the response was more rapid, with a greater reduction in suicidal ideation compared to a bipolar depression group.7,9 One case series reported 7 of 7 patients with medication-refractory mixed episode bipolar disorder responded to a trial of ECT.25 In a recent naturalistic study comprised of 522 patients with bipolar disorder, 197 patients met criteria for mixed episode and the response rate in these patients was 72.9%.9 Thus, available evidence strongly supports use of ECT in mixed episode bipolar disorder.
A Cochrane review of eight RCTs of 5,419 patients concluded that ECT was effective in the treatment of schizophrenia, with fewer relapses and better outcomes as evidenced by greater likelihood of discharge from hospital.26 Although ECT was not found to be superior to antipsychotic medications in direct comparisons, the addition of ECT to antipsychotic treatment resulted in more rapid symptom reduction and global improvement when there was limited response to medication alone. An RCT of patients with treatment-resistant symptoms persisting for more than 2 years despite trials of two antipsychotics from different pharmacological classes reported that a combination of ECT and an antipsychotic medication was of benefit in 58 of 101 participants who completed the study.27 In that study, bitemporal brief pulse ECT was administered 3 times a week up to 20 total treatments or until patients achieved the response criteria.27,28 In a recent study of patients with treatment-resistant schizophrenia, addition of an 8-week treatment course of bitemporal ECT to clozapine (stable dose for 8 weeks) led to 20% and 40% reduction in psychosis items on the Brief Psychiatric Rating Scale in 60% and 50% of participants, respectively.29 Among participants who were taking a stable dose of clozapine for 16 weeks, 73.3% of participants showed 20% reduction and 40% showed a 40% reduction in psychosis subscale scores.
In addition to treatment of the acute phase, ECT has also been studied for its utility in maintenance treatment in schizophrenia. Combination of ECT and antipsychotic medication has been shown to be significantly more effective than ECT or antipsychotic medication alone in maintaining remission at 6 months22 and 1 year.30
ECT administration techniques have also been studied in randomized trials. Efficacy did not differ when unilateral ECT treatments were administered to dominant versus nondominant side of the brain.31 Bifrontal ECT was found superior to bitemporal ECT for both efficacy and cognitive outcomes in a randomized controlled trial.32
Despite this robust empirical evidence, health care policy makers and health insurance providers have been cautious in endorsing ECT as a routine treatment for schizophrenia. The United Kingdom National Institute for Health and Care Excellence guideline on the use of ECT concluded that there was insufficient evidence to endorse the general use of ECT in the management of schizophrenia.33 At this time, the most recent practice guidelines from the World Federation of Societies of Biological Psychiatry recommends ECT only as an add-on to antipsychotic medications for treatment-resistant schizophrenia.34
Catatonia is a psychiatric emergency. First-line treatment for catatonia is generally considered to be use of high-dose benzodiazepines or barbiturates, with reported efficacy rates of 60% to 80%.35 However, although there are no existing consensus statements or treatment guidelines, ECT is considered the standard of care for medication-resistant catatonic syndromes and is often a life-saving treatment. Several professional organizations (eg, American Psychiatric Association,36 National Institute for Clinical Excellence,33 World Federation of Societies of Biological Psychiatry,35 and the International Society for Bipolar Disorders and Canadian Network for Mood And Anxiety Treatments37) recommend ECT for mood and schizophrenia spectrum disorders presenting with catatonia.
Although level 1 evidence for use of ECT in catatonia is not available, naturalistic studies and case series are promising. Reported response rates in catatonia treated with ECT range from 60% to 100%,38–41 and combination of a benzodiazepine and ECT may have a synergistic relationship in treatment of catatonia (as reported in a case series of five patients42). McCall43 found that 19 of 20 patients had resolution of catatonic mutism with combination of medication and ECT, regardless of the response to intravenous amobarbital interview, which had a 50% rate of response.
One study reported 100% efficacy of ECT as compared to antipsychotics (16%–68%) and benzodiazepine (2%).44 This study used an algorithmic approach to offer treatments to patients with catatonia. The efficacy of benzodiazepine therapy in this study was unusually low, likely due to limitation of the dose of benzodiazepine to an equivalent of 3 mg of lorazepam. Medda et al.41 treated 26 patients with medication-resistant bipolar disorder with catatonia features with ECT and noted 80.8% responded to the treatment. Suzuki et al.39,40,45 reported 100% efficacy in the treatment of catatonia secondary to schizophrenia in a series of studies that included 11 patients who showed efficacy of continuation ECT in prevention of relapse after meeting criteria for response in 4 of 7 patients during 1-year follow-up. One case series reported that patients with catatonia secondary to mood disorder showed greater clinical improvement and required fewer treatments overall than patients with catatonia secondary to schizophrenia.46 Overall, the studies suggest acute catatonia has good prognosis when benzodiazepine and/or ECT are offered, but the long-term prognosis depends on the underlying etiology of catatonia.47
It has been argued that self-injurious behavior in children and adults with autism is a sign of catatonia and that such behavior should be conceptualized as a type of stereotypy (as occurs in other catatonic syndromes).48 A recent retrospective review over a 12-year period found that 21 of 22 youths with autism diagnosed with catatonia and who did not respond to use of benzodiazepine responded to ECT.49 The number of treatments needed ranged from 16 to 688, with 13 patients requiring maintenance treatments at the end of the study due to relapse of symptoms with treatment discontinuation. Maintenance treatments ranged from every 5 to 21 days.49
Two aspects of Parkinson's disease—depression and motor symptoms—often respond to ECT.50 In a sham-controlled RCT involving 11 patients with Parkinson's disease with severe “on-off” phenomena, active ECT patients had significantly prolonged “on” phase after ECT. Due to lack of improvement in the sham-treatment group, all 11 patients in the study were administered ECT as open label, and they reported significant reduction in parkinsonian symptoms.51 A recent systematic review that included 43 published studies involving 116 patients with depression and Parkinson's disease found improvement in depression in 93% and motor symptom severity in 83% of the patients.52 Unfortunately, the benefits of ECT on motor symptoms appear to be short lived after the treatment is terminated, with reported duration ranging from few weeks to 6 months.53
Agitation in Dementia
In the past 2 decades, several published case reports, retrospective studies, case control studies, and open-label studies have reported on the use of ECT in the treatment of agitation in dementia.54 A recent review that included 17 articles on this topic found substantial benefits of ECT in 107 of 122 (88%) patients.54 Among the patients, more than one-half required maintenance treatments due to high relapse rates. Adverse effects were generally mild and transient; more severe complications such as delirium, postictal confusion, and seizure occurred in only 9 of 122 patients. Davies et al.55 have published an algorithm for agitation and aggression in Alzheimer's or mixed dementia that has been implemented at several sites in Toronto, Ontario, and ECT is recommended as the last option in the 7-step algorithm.
Refractory Status Epilepticus
Refractory status epilepticus that requires general anesthesia for management is sometimes termed “super refractory” status epilepticus. Zeiler et al.56 identified 14 articles that included 19 patients treated with ECT for refractory status epilepticus in a systematic review. Of these 19 patients, 7 had complete cessation of seizures and 4 had partial response on electroencephalogram, whereas 8 patients had no response to ECT.56 Since the review by Zeiler et al.56 was published, there have been additional articles published on this subject, with four case reports reporting efficacy with complete cessation of seizure activity after a trial of ECT in super refractory status epilepticus that failed to respond to various interventions such as anticonvulsant pharmacotherapy, general anesthesia, ketogenic diet, corticosteroids, and intravenous immunoglobulins for durations ranging from 1 to 4 months.57–60 In a recent case series of 8 patients with super refractory status epilepticus, 5 patients showed clinical evidence of improvement and required an average of eight ECT treatments.61 The available evidence supports consideration of ECT in challenging cases of refractory status epilepticus and supports the need for more systematic studies.
ECT, when considered at all, is most often thought of as an intervention for treatment-resistant depression. However, there is enough scientific support for clinicians to consider ECT in mania or mixed episodes of bipolar disorder, schizophrenia, and catatonic syndromes. There is less strong but still persuasive evidence based on case reports and retrospective reviews that support the use of ECT to address severe self-harm behaviors in patients with autism. ECT also has a role in treating other conditions, such as Parkinson's disease, agitation in dementia, and refractory status epilepticus, when other interventions have proven to be ineffective.
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