Unipolar major depression in adults: Indications for and efficacy of acute electroconvulsive therapy (ECT)

INTRODUCTION — 

Electroconvulsive therapy (ECT) uses a small electric current to produce a generalized seizure under general anesthesia. The primary indication for ECT is severe depression, but it is also used to treat other psychiatric conditions, including bipolar disorder, schizoaffective disorder, and schizophrenia [1].

The efficacy and safety of ECT is well established, and ECT is practiced throughout the world [1,2]. Nevertheless, ECT is stigmatized due to lack of knowledge about its benefits, as well as the modern techniques for administering it, which can mitigate adverse cognitive effects [1,3]. As a result, the treatment is not available in many hospitals and is underused; in the United States, approximately one to two percent of severely depressed patients receive ECT [1,4]. In some countries, legal restrictions have limited access to ECT, and misguided efforts to ban it persist [1,3,5].

The indications for treating unipolar major depression with ECT and its efficacy are reviewed here. An overview of ECT, the technique for performing ECT, medical consultation for ECT, and the indications for and efficacy of ECT in bipolar disorder are discussed separately, as is choosing initial treatment for depression and treatment of resistant depression.

●(See "Overview of electroconvulsive therapy (ECT) for adults".)

●(See "Technique for performing electroconvulsive therapy (ECT) in adults".)

●(See "Medical evaluation for electroconvulsive therapy".)

●(See "Bipolar disorder in adults: Indications for and efficacy of electroconvulsive therapy".)

●(See "Major depressive disorder in adults: Approach to initial management".)

●(See "Unipolar depression in adults: Choosing treatment for resistant depression".)

●(See "Catatonia: Treatment and prognosis".)

DEFINITIONS OF DEPRESSION — 

The term “depression” can be used in multiple ways, which can be confusing; depression may refer to a [6,7]:

●Mood state, as indicated by feelings of sadness, despair, anxiety, emptiness, discouragement, or hopelessness; having no feelings; or appearing tearful. Depressed (dysphoric) mood may be normal or a symptom of a psychopathologic syndrome or a general medical disorder.

●Syndrome, which is a constellation of symptoms and signs that may include depressed mood. Depressive syndromes that are typically encountered include major depression, minor depression, or persistent depressive disorder (dysthymia).

●Mental disorder that identifies a distinct clinical condition. As an example, the syndrome of major depression can occur in several disorders, such as unipolar major depression (also called “major depressive disorder”), bipolar disorder, schizophrenia, substance/medication-induced depressive disorder, and depressive disorder due to another (general) medical condition.

INDICATIONS — 

Referral for ECT is determined by clinical features, such as severity and urgency of current symptoms, as well as patient preference [8].

Most common indications — The primary indication for ECT is severe major depression that is treatment resistant or is life-threatening and requires a rapid response. In studies of patients who receive ECT, the mean score on the Hamilton Rating Scale for Depression (table 1) is typically >30 [9,10].

Among patients treated with ECT, the vast majority have not responded to prior trials of antidepressant medication and psychotherapy [1]. Although there are no established criteria for the number or duration of unsuccessful drug trials prior to initiating ECT, we often prescribe it for patients who fail two or three antidepressant medication trials in adequate doses for adequate duration and remain severely depressed for several months [1]. Subjecting patients to numerous (eg, five), progressively futile sequential medication trials exposes them to severe, unrelenting, and intolerable psychologic pain, which appears to be at the root of many suicide attempts. (See "Unipolar depression in adults: Choosing treatment for resistant depression" and "Suicidal ideation and behavior in adults".)

ECT provides a rapid clinical response and may thus be indicated as first-line treatment in patients with severe major depression and [1,2,11]:

●Severe suicidality, such as suicidal ideation with a plan and intent, or suicidal behavior.

●Severe psychosis, such as auditory hallucinations commanding patients to kill themselves. (See "Unipolar major depression with psychotic features: Acute treatment", section on 'First line'.)

●Catatonia, including malignant catatonia, which is characterized by fever, autonomic instability, delirium, and rigidity. (See "Catatonia: Treatment and prognosis".)

●Dehydration and malnutrition secondary to severe depression with fluid and food refusal.

●Deconditioning and pressure sores due to immobility caused by severe depression.

ECT may be preferred over pharmacotherapy:

●Debilitated or older (eg, age ≥65 years) patients who face greater risks from antidepressant and antipsychotic medication than ECT.

●Pregnant and lactating patients worried about teratogenesis and other medication side effects.

●Patient preference for ECT – As an example, patients who have a history of a depressive episode that was successfully treated with ECT after failing multiple medication trials.

ACUTE EFFICACY OF ECT

Superior outcomes — Randomized trials in severe unipolar major depression have found that the clinical effect of ECT is typically large and superior to other treatments [12-15]. As an example, a meta-analysis of 15 trials in 585 depressed patients compared ECT with a other treatments grouped together as a single comparator, including standard antidepressant medications (drugs other than ketamine-esketamine), repetitive transcranial magnetic stimulation (rTMS), cognitive-behavioral therapy, and sham or simulated ECT (anesthesia alone) [13]. The analysis found a significant effect favoring ECT over the other treatments, and the clinical effect was large.

Compared with standard antidepressants — For patients with unipolar major depression, multiple randomized trials demonstrate that ECT is superior to standard antidepressants (drugs other than ketamine-esketamine), and the clinical effect favoring ECT is large [13]:

●Based upon several trials, it is estimated that in patients with major depression who receive ECT, remission occurs in 70 to 90 percent [16-21]. By comparison, the remission rate for antidepressants (eg, citalopram) in outpatients with nonpsychotic unipolar major depression may approximate 30 percent [22,23].

●In a meta-analysis of 18 trials with 1144 depressed patients, depressive symptoms were substantially more reduced with ECT than pharmacotherapy [12]. As examples, specific trials found:

•Remission of depression with ECT compared with imipramine was 93 versus 73 percent [19].

•Marked improvement (nearly symptom free) with ECT compared with imipramine was 76 versus 49 percent [24].

•Response (reduction of baseline symptoms ≥50 percent) with ECT compared with paroxetine was 71 versus 28 percent [25].

●A subsequent meta-analysis of 8 trials (188 depressed patients) estimated that improvement on the Hamilton Rating Scale for Depression (table 1) was five points (95% CI 0.8-9.1) greater in patients who received ECT than standard antidepressant medication [15]. Although this represented a clinically large difference, it may nevertheless have substantially underestimated the benefit of ECT [26,27].

Compared with other neuromodulation interventions — Based upon randomized trials, the probability of response in patients with unipolar major depression is greater with ECT than other neuromodulation interventions. A network meta-analysis identified 113 randomized trials that evaluated the efficacy of different nonsurgical brain stimulation interventions in patients with major depression (n >6700); the interventions included ECT, repetitive transcranial magnetic stimulation (TMS), magnetic seizure therapy, and transcranial direct current stimulation [28]. The analysis ranked the interventions by efficacy, using direct comparisons of the interventions, as well as indirect comparisons through their relative effect with a common comparator (typically sham therapy). Based primarily on analysis of indirect comparisons, the probability of response was greatest with ECT.

Compared with transcranial magnetic stimulation — For patients with treatment-resistant major depression, ECT is more efficacious than repetitive TMS. (See "Unipolar depression in adults: Choosing treatment for resistant depression", section on 'Next step treatment'.)

Additional information about repetitive TMS is discussed separately. (See "Unipolar depression in adults: Indications, efficacy, and safety of transcranial magnetic stimulation (TMS)".)

Compared with sham ECT — ECT is superior to sham ECT (anesthesia alone) for major depression, based upon a network meta-analysis of 113 randomized trials that compared nonsurgical brain stimulation with sham therapy (n >6700 patients) [28]. The analysis evaluated the relative efficacy of ECT and sham therapy by using results from direct comparisons of the two, as well as indirectly comparing ECT and sham therapy through their relative effect with a common comparator (eg, TMS). Response was far more likely with ECT than sham therapy, including:

●Bilateral ECT (odds ratio 9, 95% CI 3-31)

●High dose right unilateral ECT (odds ratio 7, 95% CI 2-28)

Rapid clinical response — Many patients with major depression, including older patients, remit quickly with ECT [20]. Response typically begins to occur after two to four treatments. Some patients experience an immediate improvement in symptoms after the first ECT session, and there is evidence that the initial treatment may be more potent than subsequent sessions [11]. Rarely, depression will remit with a single ECT treatment [29,30].

In a prospective observational study of 253 patients with unipolar major depression who were treated three times per week with bilateral ECT, the median time to first response (>50 percent reduction of baseline depression rating scale score) was one week (three ECT treatments) [16]. Remission occurred in:

●4 percent of patients at or before ECT number 3 (week 1)

●34 percent at or before ECT number 6 (week 2)

●60 percent at or before ECT number 9 (week 3)

Among specific depressive symptoms, suicidal ideation and behavior often improve quickly with ECT [31]. Disturbed sleep and appetite, and low energy may respond before mood, guilt, and worthlessness.

The speed of response with ECT contrasts with that for pharmacotherapy in less severely ill outpatients with major depression. Only approximately 66 percent of medication responses occur within four weeks of starting treatment, and remission may not occur for weeks to months following response [16].

Durability of response to acute ECT — Following successful treatment with acute ECT, relapse is common. Nevertheless, among patients who are hospitalized for unipolar major depression and then discharged, fewer readmissions occur in those who received ECT [4].

●Risk of relapse following ECT – Most patients with major depression who respond to ECT will subsequently relapse, if they do not receive continuation and maintenance treatment with pharmacotherapy or ECT [32,33]. Thus, continuation/maintenance treatment is nearly always indicated following a successful course of acute ECT. Evidence supporting the use of continuation pharmacotherapy includes a meta-analysis of seven randomized trials, which compared antidepressants with placebo in depressed patients successfully treated with ECT (n >400); antidepressants reduced the risk of relapse by 50 percent (relative risk 0.5, 95% CI 0.4-0.6) [32].

However, many patients who respond to acute ECT will relapse despite continuation pharmacotherapy. In a meta-analysis of 17 randomized trials and observational studies of patients who initiated continuation pharmacotherapy following ECT (n >700), relapse occurred in 38 percent within six months [32].

Additional information about the efficacy of continuation/maintenance treatment with antidepressants or ECT is discussed separately. (See "Major depressive disorder in adults: Continuation and maintenance treatment", section on 'Antidepressant medications' and "Overview of electroconvulsive therapy (ECT) for adults", section on 'Continuation and maintenance ECT'.)

●Fewer hospital readmissions – For patients who are hospitalized with unipolar major depression, ECT is associated with fewer short-term readmissions for psychiatric care. A study of administrative health care datasets identified general hospital inpatients with a principle diagnosis of major depression, who either received ECT (n >1500) or did not (n >66,000) [4]. Following discharge, readmission within 30 days occurred in fewer patients treated with ECT (5 versus 10 percent; relative risk 0.5, 95% CI 0.3-0.8).

Late-life depression — Reviews of numerous studies have found that ECT is efficacious and safe for late-life depression, including patients who are very old (eg, age >85 years) [34,35]. As an example:

●Efficacy – One randomized trial compared ECT with simulated/sham ECT (anesthesia alone) in older depressed patients who completed six treatments (n = 23), and found that improvement was greater with ECT [36].

A prospective observational study enrolled 240 patients (mean age 70 years) with unipolar major depression and treated them with venlafaxine (target dose 225 mg/day) plus right unilateral, ultrabrief pulse ECT three times per week [37]. Remission occurred in 62 percent of patients; the mean number of ECT treatments in patients who remitted was 7.3 and the mean time to remission was thus approximately 2.5 weeks. In addition, global cognitive functioning at baseline and post-ECT was comparable.

●Speed of response – Prospective observational studies have found that older age patients with psychotic depression (n = 25) were more likely to remit with ECT compared with nortriptyline plus phenelzine [38], and that older age patients hospitalized for unipolar depression (n = 128) remitted more quickly with ECT than nortriptyline or venlafaxine [39].

●Mortality – A retrospective study of older patients hospitalized for depression (n = 192) found that during the subsequent five years, mortality was less in patients who were treated with ECT during the hospitalization, compared with patients treated with pharmacotherapy [40].

In addition, ECT is particularly helpful for older age, depressed patients who have contraindications to antidepressant medications, do not tolerate or respond to medications, cannot participate in psychotherapy or do not respond to it, or who develop severe symptoms and complications of depression that require immediate relief [1,41].

Many older age patients suffer poststroke depression after an acute cerebrovascular event [42]. A small, retrospective study of medically ill geriatric patients with poststroke depression (n = 20) found that ECT was effective and well tolerated for 95 percent [43]. However, it is not clear whether vascular depression, which occurs in association with chronic ischemic changes in the brain, responds well to ECT [42].

Additional information about late-life depression is discussed elsewhere. (See "Diagnosis and management of late-life depression".)

Ketamine anesthesia — Ketamine has been used as an alternative or adjunctive anesthetic for ECT since at least 1969, and may enhance efficacy early in the course of ECT [44,45]. However, the benefit of ketamine dissipates, such that post-ECT outcomes with or without ketamine anesthesia are comparable, because the efficacy of ECT is so large. Nevertheless, ketamine anesthesia may be indicated for patients who require faster improvement of depressive symptoms, including suicidal ideation with a plan and intent.

Based upon randomized trials, inducing general anesthesia with adjunctive ketamine can enhance the effect of ECT in the short-term, but not throughout the course of treatment:

●In a systematic review that identified 17 trials in patients with unipolar major depression (n >1000) who were treated with ECT, meta-analyses compared ketamine plus either propofol or thiopental with thiopental monotherapy or propofol monotherapy [45]. The primary findings included the following:

•One to two weeks after commencing ECT, improvement of depression was greater with adjunctive ketamine. However, the clinical effect was small.

•Following ECT, improvement was comparable with or without adjunctive ketamine.

●A subsequent trial compared adjunctive ketamine with saline in 127 patients who were treated with ECT for unipolar major depression and received propofol anesthesia [46]:

•The median time to response (reduction of baseline depression ≥50 percent) was faster with ketamine than saline (four versus seven ECT treatments).

•The median time to resolution of active suicidal ideation was faster with ketamine (three versus six treatments).

•Post-ECT, response and resolution of suicidal ideation were each comparable with adjunctive ketamine and saline.

Adverse effects that may be associated with using ketamine as an induction agent include post-ECT disorientation, restlessness, dissociation, dizziness, delirium, psychosis, nausea, and/or vomiting [47,48]. In addition, ketamine can increase blood pressure at higher doses and should thus be used cautiously in patients with a history of cardiovascular disease. One trial administered ketamine to 12 patients at a dose of 0.8 mg/kg, and diastolic blood pressure >100 mgHg occurred during ECT in five cases (42 percent) [49]. Another trial found that systolic and diastolic blood pressures were often greater in patients who received ketamine monotherapy (1 to 2 mg/kg), compared with thiopental [50].

The short-term benefit of adjunctive ketamine may lie in its ability to prolong or enhance ECT seizures, because it is less anticonvulsant than other anesthetics [51]. A meta-analysis of randomized trials compared anesthetic regimens that included ketamine with regimens that did not, and found that ketamine prolonged seizure duration by 11.5 seconds, a significant and clinically moderate to large benefit [48]. In a subsequent meta-analysis, anesthesia that included ketamine also led to longer seizure activity [45].

Anesthesia for ECT is discussed separately. (See "Technique for performing electroconvulsive therapy (ECT) in adults", section on 'Anesthesia technique'.)

EFFICACY OF MAINTENANCE ECT — 

The administration and efficacy of continuation and maintenance ECT is discussed separately. (See "Overview of electroconvulsive therapy (ECT) for adults", section on 'Continuation and maintenance ECT'.)

ADVERSE EFFECTS OF ECT — 

The adverse effects of ECT may be divided into general medical and cognitive effects. Medical effects include cardiopulmonary events, aspiration pneumonia, fractures, dental and tongue injuries, headache, and nausea; these are uncommon and largely preventable.

Adverse cognitive effects are common and include acute confusion, anterograde amnesia, and retrograde amnesia; these are generally short-lived.

Additional information about the adverse effects of ECT are discussed separately. (See "Overview of electroconvulsive therapy (ECT) for adults", section on 'Adverse effects'.)

PREDICTORS OF RESPONSE — 

Among patients with unipolar major depression, multiple clinical factors predict a good response to ECT.

Older age — In depressed patients treated with ECT, older age is associated with better outcomes [1,15,20]. A meta-analysis of 34 prospective or retrospective observational studies (n >3200 patients) found that response to ECT was more likely to occur in patients who were older (eg, age ≥60 years), compared with younger patients [52]. As an example, an prospective observational study of patients with major depression who were treated with bilateral ECT three times per week compared response in three age groups: younger (age 18 to 45 years, n = 79), middle-aged (age 46 to 64, n = 81), and older age (age 65 to 85, n = 93) [53]. The analyses found that remission occurred in more middle-aged or older age patients compared with younger patients (86 and 80 versus 57 percent). In addition, greater age (as a continuous variable) was associated with lower depression rating scale scores.

One study found that ECT was used approximately three times more often in older adults (>65 years) than younger adults [54].

Severe depression — Based upon a meta-analysis of 34 prospective or retrospective observational studies (n >3200 patients), response to ECT is more likely to occur in patients with more severe episodes (eg, a Patient Health Questionnaire [PHQ-9] score ≥20 (table 2)) [52].

Psychotic depression — ECT is particularly useful for psychotic depression [1]. (See "Unipolar major depression with psychotic features: Acute treatment", section on 'Electroconvulsive therapy'.)

Catatonia — ECT is a first-line treatment for catatonia [1]. (See "Catatonia: Treatment and prognosis".)

Atypical depression — Based upon one observational study, ECT may be as effective or better in atypical depression (mood reactivity, hyperphagia or increased weight, hypersomnia, leaden paralysis, and interpersonal rejection sensitivity), compared with typical depression. Among patients with unipolar major depression who were treated with bilateral ECT three times per week, higher rates of remission occurred in patients with atypical depression (n = 36) compared to patients with typical depression (n = 453; 81 versus 67 percent) [55].

Information about atypical depression is discussed elsewhere. (See "Depression in adults: Clinical features and diagnosis", section on 'Specific symptom constellations'.)

Absence of comorbid borderline personality disorder — Absence of comorbid borderline personality disorder appears to be associated with increased ECT efficacy, whereas comorbid personality disorders other than borderline personality disorder do not seem to diminish ECT’s efficacy [56,57]. A review of five observational studies found that in four studies, response to ECT in depressed patients was more robust in those without borderline personality disorder, compared to those with borderline personality disorder [57]. As an example, a prospective study found that remission with ECT occurred in more depressed patients without comorbid personality disorders (n = 77), and depressed patients with personality disorders other than borderline personality disorder (n = 42), compared to depressed patients with comorbid borderline personality disorder (n = 20; 65 and 52 versus 20 percent) [58]. Remission in the group with no personality disorder and the group with other personality disorders was comparable.

Although patients with unipolar major depression plus comorbid borderline personality disorder are less likely to respond to ECT, these patients may nevertheless be candidates for ECT. The key is to establish that the patient has major depression, which can be difficult to distinguish from affective instability, one of the core features of borderline personality disorder. (See "Borderline personality disorder: Epidemiology, pathogenesis, clinical features, course, assessment, and diagnosis", section on 'Affective instability'.)

Additional information about treating co-occurring depression and borderline personality disorder is discussed separately. (See "Borderline personality disorder: Treatment overview", section on 'Depression and anxiety'.)

Absence of medication failures — Nonresponse to at least one antidepressant (medication failure) during the current depressive episode is associated with poorer response to ECT. In a pooled analysis of 11 observational studies of depressed patients (n >1100), response to ECT occurred in fewer patients with medication failure than patients without medication failure (58 versus 70) [59].

Shorter duration of the depressive episode — A shorter duration of the major depressive episode appears to be associated with increased efficacy of ECT [1,56]. In a pooled analysis of seven observational studies (n >700 patients with depression), the mean duration of the episode was shorter in patients who responded to ECT than patients who did not respond (7 versus 14 months) [59].

Shorter depressive episodes and absence of medication failure may be correlated as favorable prognostic factors for ECT, and when appropriate, these factors favor prescribing ECT earlier in a depressive episode.

Early improvement — Early improvement after six ECT sessions appears to be associated with remission by the end of treatment, suggesting that clinicians should continue ECT [16]. As an example, a prospective study of inpatients with unipolar major depression (n = 130) found that among patients with early improvement (defined as reduction of baseline symptoms by 20 to 30 percent), remission ultimately occurred in 73 percent (positive predictive value) [60]. Regardless, we continue to administer ECT in patients without early improvement because a substantial proportion of these patients subsequently remit [16,60].

Biomarkers — Prescribing ECT on the basis of biomarkers is not standard practice, because there are no biologic predictors of sufficient utility to identify which patients are most likely to respond to ECT [1]. Nevertheless, relatively small, preliminary neuroimaging studies have found that differences in central nervous system structure and functioning are associated with better responses to ECT [61]. As an example, prospective functional magnetic resonance imaging of neural networks centered in the dorsomedial prefrontal cortex and in the anterior cingulate cortex in 45 patients with treatment-resistant depression found that images in each network provided good sensitivity, specificity, and positive predictive value in predicting recovery with ECT [62].

Other biomarkers that are associated with increased rates of response to ECT include hyperconnectivity between key areas of brain circuitry involved in depression (eg, anterior cingulate cortex and the dorsolateral prefrontal cortex), reduced glutamine/glutamate levels in the anterior cingulate cortex, and high plasma homovanillic acid levels and tumor necrosis factor [63]. In addition, multiple genetic polymorphisms are associated with a good response to ECT.

TREATMENT GUIDELINES — 

Multiple treatment guidelines recommend using ECT as first-line treatment for life-threatening, severe major depressive episodes that require a rapid clinical response [1]. In addition, the guidelines suggest using ECT for depressive episodes that do not respond to pharmacotherapy and/or psychotherapy. The guidelines include those issued by the American Psychiatric Association, British Association for Psychopharmacology, Canadian Network for Mood and Anxiety Treatments, Royal Australian and New Zealand College of Psychiatrists, and the United States Veterans Affairs and Department of Defense [17,64-67].

COST EFFECTIVENESS — 

The cost effectiveness of ECT compared with pharmacotherapy is not clear, due to the lack of randomized trials that have evaluated this issue [68]. However, a health economics study, which integrated published data to simulate treatment of major depression in varying scenarios, found that ECT was cost-effective after patients had not responded to two or more courses of pharmacotherapy and/or psychotherapy [69]. In addition, a randomized trial that compared ECT with transcranial magnetic stimulation found that the average total costs during treatment and the six-month follow-up period were less for ECT [70].

SOCIETY GUIDELINE LINKS — 

Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Depressive disorders".)

INFORMATION FOR PATIENTS — 

UpToDate offers two types of patient education materials, “The Basics” and “Beyond the Basics.” The Basics patient education pieces are written in plain language, at the 5^th to 6^th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10^th to 12^th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on “patient info” and the keyword(s) of interest.)

●Basics topics (see "Patient education: Electroconvulsive therapy (ECT) (The Basics)")

●Beyond the Basics topics (see "Patient education: Electroconvulsive therapy (ECT) (Beyond the Basics)")

OTHER RESOURCES FOR PATIENT EDUCATION — 

One of the requirements for obtaining informed consent for any treatment, including ECT, is that patients receive adequate information about the procedure. Written material is available at this website for patients and family members to augment discussions with the psychiatrist.

Educational material explaining ECT is also available as part of a document entitled "Brain Stimulation Therapies" that is published by the National Institute of Mental Health. This publication can be obtained through a toll-free number, 866-615-646, or online at this website. The website also provides information about depression in language intended for the lay public.

SUMMARY

●Indications – The primary indication for electroconvulsive therapy (ECT) is severe major depression. Other indications include bipolar disorder, schizoaffective disorder, and schizophrenia. First-line treatment with ECT for these disorders may be warranted in clinical situations that include:

•Suicidal ideation and behavior

•Psychosis

•Catatonia

•Dehydration and malnutrition secondary to fluid and food refusal

•Debilitated or older patients who face greater risks from antidepressant and antipsychotic medication than ECT

(See 'Indications' above.)

●Acute efficacy of ECT – Randomized trials in severe unipolar major depression have found that the clinical effect of ECT is typically large and superior to other treatments. (See 'Acute efficacy of ECT' above.)

•Compared with standard antidepressants – For patients with major depression, multiple randomized trials demonstrate that ECT is superior to standard antidepressants (drugs other than ketamine-esketamine). Remission occurs in 70 to 90 percent of patients who receive ECT, whereas the remission rate for antidepressants may approximate 30 percent. (See 'Compared with standard antidepressants' above.)

•Compared with other neuromodulation interventions – The probability of response in patients with unipolar major depression is greater with ECT than other neuromodulation interventions, including repetitive transcranial magnetic stimulation, magnetic seizure therapy, and transcranial direct current stimulation. (See 'Compared with other neuromodulation interventions' above.)

●Adverse effects – The adverse effects of ECT may be divided into general medical and cognitive effects. Medical effects include cardiopulmonary events, aspiration pneumonia, and fractures; cognitive effects include acute confusion, anterograde amnesia, and retrograde amnesia. (See "Overview of electroconvulsive therapy (ECT) for adults", section on 'Adverse effects'.)

●Predictors of response – Among patients with unipolar major depression, multiple clinical factors are associated with a good response to ECT, including older age, relatively severe symptoms, absence of comorbid borderline personality disorder, and early improvement with ECT. (See 'Predictors of response' above.)

●Treatment guidelines – Multiple treatment guidelines recommend using ECT as first-line treatment for life-threatening depressive or treatment-resistant episodes. (See 'Treatment guidelines' above.)