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Mental Health Disorders

What Do We Know About Electroconvulsive Therapy?

Hani Raoul Khouzam, MD, MPH

ABSTRACT: In this first half of a 2-part series, this article summarizes the history of electroconvulsive therapy (ECT), the proposed mechanisms of action, and its clinical indications. The goal is to encourage primary care providers to consider ECT referral as a first-line and only viable treatment for patients when medication is not an option, in cases of recurrent conditions with past success with ECT, and in patients who prefer ECT over medication.


 

There have been significant advances in the technology used for electroconvulsive therapy (ECT). Many recent studies have concluded that the use of ECT is a safe and effective treatment for several psychiatric and medical conditions. Clinical practice published guidelines have also contributed to the implementation of the high standards of modern ECT administration.

However, ECT remains a controversial treatment largely due to its negative and sensational portrayal in the media. Many clinicians consider ECT a treatment of last resort for patients with ineffective or poorly tolerated response to psychiatric medications, although the procedure itself is simple and can be performed on a highly diverse patient population with severe psychiatric and medical conditions. 

In comparison to medication, ECT can lead to a substantial, effective, and rapid clinical improvement, particularly in the severely ill, elderly, and physically debilitated populations. modern ECT techniques are performed under general anesthesia and use muscle relaxation, and the selective passage of an electrical current through the brain which induces modified seizures to achieve the intended therapeutic purposes. 
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History

Hippocrates, who is considered one of the father’s of Western medicine, documented the amazing cure of an insane patient following malaria-induced seizures.1 In the1500s, the Swiss alchemist and physician Phillipus Paracelsus induced seizures with oral camphor to treat mania and psychosis.2 

In 1785, the use of camphor induced seizure to treat mania was first published.3 In the 1920s,1 the Viennese physician Manfred Sakel documented the beneficial effects of insulin shock therapy/insulin-induced hypoglycemic seizure in the treatment of patients with schizophrenia, however this practice was later discontinued due to its severe unwarranted medical complications. 

In 1934, the Hungarian physician and neuropsychiatrist Ladislas von Meduna postulated an inherent biological antagonism between schizophrenia and epilepsy and reported beneficial effects of seizures induced by camphor in a patient with schizophrenia and catatonia.4 This form of convulsive therapy, although efficacious, was extremely unpleasant. In 1937, the Italian physicians Ugo Cerletti and Lucio Bini used a relatively comfortable electrical model of seizure induction and successfully treated a patient with catatonic schizophrenia.5,6 After more trials, ECT rapidly replaced chemically-induced convulsive therapy throughout the world.1,6 Later, ECT was used for the treatment of depression.7-11 

As ECT methodology became more refined, especially with the use of neuromuscular blockers and anaesthesia to improve safety, practitioners became more willing to use it—particularly for patients who do not respond to pharmacological interventions and in cases where pharmacological intervention is contraindicated.6-11 

Hollywood movies including House on Haunted Hill, Requiem for a Dream, and especially One Flew Over the Cuckoo's Nest, based on 1962 novel by Ken Kesey, have negatively portrayed ECT as a cruel punishment, which in turn has contributed to its stigmatization in the world of public opinion.12 

However, the relative safety, effectiveness, and fast mode of action has led the American Psychiatric Association (APA) to establish clear and special guidelines to support the clinical use of ECT.7 Similar guidelines have been established by other professional associations in Australia, Austria, Canada, Denmark, India, Germany, Netherlands, and New Zealand, to name a few countries around the world.13,14 Despite ECT consistent evidence-based effectiveness, there has been a dramatic decline in use in the United States over the past 15 years.15 

ECT Mechanism of Action 

Many theories have been offered to account for the efficacy of ECT, particularly in uncovering its mode of action since ECT produces a wide variety of effects on neurophysiologic, neurotransmitter, and neuroendocrine systems. Here is a breakdown of the historical and modern theories that have been suggested:  

Psychoanalytic theories.6,16 This subcategory includes fear, regression, and punishment theories. The fear theory postulated that the fear of ECT led to the remission of symptoms. The regression theory suggested that ECT-induced regression to earlier infantile behaviors provided its therapeutic benefit. The punishment theory postulated that for self-loathing and guilty patients, ECT may provide a mean of fulfilling the ego needs to punish the id in order to regain the superego approval. 

Note: With the increased reliance on evidence-based practices, the psychoanalytic theories of ECT are mentioned due to their historical importance rather than their clinical relevance.16

• Amnestic theory. This theory suggests that ECT beneficial effects are attributed to its amnesic or “bad memories eraser” experiences from the distant past.17 However, recent ECT technical advancements have reduced amnesia, thus refuting this theory.18,19 

Brain damage theory. This theory was based on retrospective studies that showed similar findings on the Rorschach’s test in subjects with diffuse brain damage and those who undergone ECT.20 Subsequent review of brain structure research using animal and human autopsy case reports did not show any evidence that ECT can lead to structural brain damage.18 

The modern theories of ECT mechanism of action include the generalized seizure (anticonvulsant) threshold, neuroendocrine dysfunction, and increased hippocampal neurogenesis and synaptogenesis theories.

Generalized seizure (anticonvulsant) threshold theory. Several decades of clinical experiences demonstrated that increasing seizure thresholds during a course of ECT is associated with its clinical response and the induction of a bilateral generalized seizure is required for both the beneficial and adverse effects of ECT.21

• Neuroendocrine dysfunction theory. This theory is based on the idea that every neurotransmitter system, including beta-adrenergic, serotonin, muscarinic, cholinergic, and dopaminergic systems as well as brain-derived neurotrophic factor (BDNF), second-messenger systems, and catechol-O-methyltransferase (COMT) polymorphisms are affected by ECT and that ECT effects are associated with the normalization of all these systems.22-29 

Researchers have not been able to correlate ECT effects on the neuroendocrine system with therapeutic outcomes since several psychiatric conditions treated with ECT did not show any neuroendocrine dysfunction prior to receiving ECT.30-36 

Hippocampal neurogenesis and synaptogenesis theory. This theory hypothesize that ECT lead to an induction of neurotropic factors, resulting in hippocampal neurogenesis.37,38 These findings have heightened interest in studying hippocampal structure and function in experimental animals, which have shown increased hippocampal neurogenesis and synaptogenesis—especially during and after ECT administration.39 

Further studies of neurotropic factors have also supported the role of neuroplasticity related to ECT in humans.40,41 MRI studies conducted prior to and 1-week post-ECT have shown an increase in both right and left hippocampal volume.42 

However, despite all these suggested theories, the exact mechanism of action of ECT remains unknown.

(Next Page: ECT Clinical Indications)

ECT Clinical Indications16,35,43

Typically, ECT is clinically indicated for patients suffering from severe depression after multiple attempts to treat their illness with medications have failed. It may be also used in the following clinical presentations: 

• The need for rapid, definitive response due to the severity of a psychiatric or medical conditions

• The risks of other treatments outweigh the risks of ECT 

• The history of poor medication response or good ECT response in 1 or more previous episodes of illness 

• Patient preference 

In other conditions, ECT should be considered based on at least 1 of the following: 

• Treatment resistance, which is established following the appropriate medications choice, recommended dosing, duration of treatment, and adequate monitoring of compliance and adherence. 

• Adverse or intolerant medication effects, which are considered less likely to emerge with ECT. 

• Deterioration of the patient’s psychiatric or medical condition creating a need for a rapid, definitive response.

ECT and Psychiatric Conditions

The following diagnoses have shown compelling data and a strong consensus supporting the efficacy of ECT. 

Major depressive disorder. ECT is an effective treatment for all subtypes of unipolar major depression, including major depression single episode and recurrent major depression.6-10,43 It should be considered for patients in the acute phase of major depressive disorder who have a high degree of symptom severity and functional impairment or who have depression with psychotic symptoms or depression with catatonia.6-10,34,44 

 ECT may also be the treatment of choice for patients in whom treatment response is urgently needed, such as patients who are suicidal or those who are refusing food and are nutritionally compromised.6-10,43-45 ECT should be considered for treatment of severe depression and co-occurring medical conditions that require an early treatment response and also during pregnancy to prevent harmful or adverse effects of medications on fetal development.6-8,46 

ECT needs to be also considered in patients with melancholia48 and unspecified depressive disorder (eg, atypical depression).48 

Clinical evidence has consistently shown ECT to be viable treatment option for patients with major depression regardless of the presence or absence of psychosis, retardation, and/or agitation. 46,48,49 The remission rate with ECT is 60% to 80% in patients who are treated for major depression and is more effective than pharmacotherapy.6-10,45-48 It is important for clinicians to know and realize that ECT effectiveness in treatment resistant serious depression remains superior to other available alternative treatment interventions. 

Bipolar mood disorder. ECT is an effective treatment for all subtypes of bipolar disorder, including bipolar disorder depressed, bipolar disorder manic, mixed bipolar, and unspecified bipolar disorders.49,50 ECT could be also considered for treatment of mania during pregnancy to prevent harmful or adverse effects of medications on fetal development.7 ECT could also be efficacious in patients with rapid cycling bipolar disorder.51 

As in the case of depression, ECT should be considered in bipolar patients with life-threatening conditions who are refusing food and fluid intake, in individuals with suicidal intention and plans,7,43 and those with psychosis.43,52 

ECT is considered a safer alternative to medications for patients with bipolar disorder and co-occurring medical conditions, and particularly in the elderly.7,47,53 In contrast to antidepressant medications, the precipitation of mania due to ECT is considered relatively rare.7,51,54 The overall remission rate with ECT is 65% to 70% for patients with bipolar depression and the remission rate with ECT is 53% to 56% in patients with bipolar mania.55-57

Dysthymic disorder (dysthymia). ECT may provide an effective intervention for patients with long history of dysthymic disorder and major depression (ie, double depression), who have not responded to other alternative treatments.45,48,58 

Schizophrenia and other psychotic disorders. ECT could be considered during exacerbations of psychotic symptoms in patients with schizophrenia in any of the following situations:7,44,45 

o In combination with antipsychotics, for patients with severe psychosis that has not responded to treatment with antipsychotic medications alone

o When marked positive and affective symptoms are present 

o When catatonia is the predominant clinical presentation 

o Past history of a favorable ECT response 

ECT is effective in other psychotic disorders, including schizophreniform and schizoaffective disorders as well as unspecified psychotic disorders.6,17,22 ECT can also be effective in the management of severe mood and psychotic conditions that are a result of a medical conditions—eg, toxic and metabolic delirium, especially if associated with catatonic states. Although the clinical evidence supports some benefits in regard to improvement of acute symptoms of schizophrenia compared with placebo, ECT is not as effective in chronic schizophrenia.31 

In combination with antipsychotics, ECT may be considered for patients with severe psychosis that have not responded to treatment with antipsychotic medications.7,59 Clinical evidence has shown ECT to be a safe and effective intervention in adolescent patients with schizophrenia spectrum disorders (SSD).60

Trauma and stressor-related disorders. In 2013, the APA revised the PTSD diagnostic criteria to include a new category of trauma and stress¬or-related disorders.61 ECT may improve the core symptoms of PTSD independent of improvement in depression, and may therefore be a useful treatment option for patients with severe, chronic, medication, and psychotherapy refractory PTSD.62 

(Next Page: ECT and Non-Psychiatric Medical Conditions)

ECT and Non-Psychiatric Medical Conditions 

Parkinson’s disease (PD). Patients resistant to or who are intolerant to antiparkinsonian medications, or those who developed psychosis or other severe behavioral changes that are resistant to antipsychotic medications, frequently benefit from ECT.63 Improvements are often in the motor functioning domain, especially in those with “on-off” phenomenon and are independent of the benefits observed for PD symptoms of depression.63,64 

The ECT neuromuscular benefits have been found to persist for days to months, allowing better management of refractory advanced PD with less dopaminergic medications. These responses are due to ECT effects on increasing the dopaminergic tone without precipitating psychosis. The predictors of a favorable response include medication-refractory patients, advanced age, severe disability, and long duration of treatment with levodopa. ECT is also beneficial for patients with PD who are severely depressed and whose depression is refractory to antidepressant medications.64 

Neuroleptic malignant syndrome (NMS). This rare but life-threatening, idiosyncratic reaction to antipsychotic (neuroleptic) medications has also been associated with non-narcoleptic agents that block central dopamine pathways, such as metoclopramide, amoxapine, and lithium.65 The syndrome is characterized by fever, muscular rigidity, altered mental status, and autonomic dysfunction. 

ECT is the preferred treatment of choice in cases of severe NMS, especially if the underlying psychiatric diagnosis is depression with psychotic features, and in cases where malignant (lethal) catatonia cannot be ruled out. It can help with the alteration of temperature, level of consciousness, and diaphoresis. It may also be useful in treating the underlying psychiatric disease in patients who are unable to take antipsychotics. ECT with anesthesia has generally been safe with no increased incidence of malignant hyperthermia.66,67

Malignant catatonia. Malignant catatonia is another life-threatening neuropsychiatric disorder, characterized by psychosis with elevated temperature, autonomic instability, hyperactivity, mutism, and stuperous exhaustion. Although historically nearly always fatal, there has been a recent decline in malignant catatonia mortality, due to earlier diagnoses and appropriate treatment implementation. The catatonia usually resolve with timely pharmacological intervention with benzodiazepines, however if catatonia persists, ECT is considered the next and most appropriate treatment. 68

Essential tremor (ET). This is a visible postural tremor of hands and forearms that may include a kinetic component. It is the most common movement disorder worldwide; prevalence ranges from 4.1 to 39.2 cases per 1000 persons to as high as 50.5 per 1000 in persons age 60 and older.69 The tremor may start in a single limb, but it becomes bilateral over time—most often as a flexion-extension movement of the wrist with a frequency of 4 Hz to 12 Hz. 

It may involve the head, appearing as a yes-yes or no-no head movement. Amplitude increases with stress, fatigue, and certain medications (eg, central nervous system stimulants) and may increase with certain voluntary activities (eg, holding a fork or cup). Rest and certain medications, such as the anticholinergics, beta blockers, and primidone, may decrease the tremor.70 Patients who do not to respond to these medications or are unable to tolerate their side effects could respond well to ECT.71

Intractable seizure disorder. Because paradoxically ECT has also anticonvulsant effects, it may improve seizure control in epilepsy, especially in patients with intractable epilepsy or status epilepticus that are unresponsive to anticonvulsant medications and are not suitable candidates for brain surgery.71-73

Dementia. ECT is generally contraindicated in the treatment of dementia due to its cognitive side effects. It has been used in the treatment of dementia-related aggressive behavior, general agitation or screaming, and in patients with prominent depressive symptoms associated with Alzheimer's disease and other dementias.74 The mood-improving effects of ECT in patients with dementia are comparable to patients without dementia.75 

Patients with subcortical dementias (eg, PD, Huntington’s disease, normal pressure hydrocephalus) usually respond better than individuals with cortical dementias (eg, Alzheimer and Pick’s diseases). Transient post-ECT confusion usually and spontaneously remits and cognitive improvement occurs due to the improvement of depression-related cognitive effects, which is sometime described in the literature as the dementia spectrum of depression or pseudodementia.76,77 

Delirium. Although there is a possible risk for post-ECT delirium, ECT could be considered for delirious patients who require urgent management when the initiated medical treatment could not reverse the specific cause of the delirium. In these cases of persistent delirium, ECT could lead to an immediate improvement in the delirious symptoms of psychomotor retardation,hallucinations and delusions.7 Delirious mania, also known as Bell mania, is an acute syndrome of excitement, delirium, and psychosis that could also respond to ECT.78

Pregnancy and postpartum period. Following appropriate anaesthesia and obstetrical consultations, ECT is considered a safe alternative to pharmacological treatment and effective treatment in all stages of pregnancy, particularly with near term high-risk potential for recurrent depressive episodes.7,79 ECT is also considered a safe and effective treatment in the postpartum period since anaesthetic agents pose little risk to the nursing infant.7,46,79

Congenital and acquired brain injury. Patients with congenital and acquired brain injury with intellectual disabilities who have treatment-resistant mood or psychotic disorders could benefit from ECT. These patients have a higher risk for post-ECT delirium and would require adjustments in technique and/or frequency of ECT treatments. ECT can be a safe and effective treatment alternative especially in cases where the adverse effects associated with pharmacological treatment are not well tolerated.7,80

Chronic pain syndromes. ECT have been used as a treatment option for certain patients with chronic pain who have not responded to other treatment interventions, and especially in those with social disability associated with multiple chemical sensitivities.81,82 More studies are needed to evaluate if ECT can be recommended as a treatment option for chronic pain syndromes.

Hypopituitarism. In addition to its effectiveness in treatment-resistant depression associated with hypothyroidism, ECT can be an effective treatment for persistent hypothalamic-pituitary suppression, even in the absence of a psychiatric disorder.80,83

Elderly patients. Aside from physiological considerations during and immediately after anaesthesia, being elderly in itself confers no specific risk for ECT, and may in fact predict a favorable response when compared to younger adults.7,45,75,84

Children and adolescents. Treating children and adolescents with ECT should be considered according to the American Academy of Child and Adolescent Psychiatry (AACAP) ethics committee only when symptoms are severe, persistent, significantly disabling, or in cases of life-threatening conditions (eg, refusal to eat or drink, uncontrollable mania, and florid psychosis). 

Except in the case of utmost urgency, the psychiatrist must document failure of response or intolerance to at least two adequate trials of psychotropic medications. Although resource availability, consent, and psychiatric attitudes towards ECT for this age group are potentially limiting further study in this population, ECT can reduce morbidity and mortality in this age group.61,85

This first half of a 2-part series summarized the use of ECT in the treatment of several psychiatric and medical conditions. However, the efficacy of ECT is not reflected in current practices within the United States, where ECT is often considered a last resort. Several studies have confirmed the significant superiority of ECT, especially for major depressive disorder, bipolar disorder, psychosis, suicidality, catatonia, and in the medically-compromised patients. 

Next month, we will discuss methods of ECT administration, adverse effects, and treatment options.

Hani Raoul Khouzam, MD, MPH, is a health sciences clinical professor of psychiatry at the University of California San Francisco (UCSF) Fresno Medical Education Program and a psychiatrist at the VACCHCS in Fresnco, CA. He was a consultant psychiatrist at the Matariki Community Mental Health Centre in counties Manukau, New Zealand. 

Acknowledgements: The author would like to thank the committee members of the electroconvulsive treatment program at the Veterans Affairs Central California Health Care System, including Director Avak A. Howsepian, MD, Chair Robert Emes, and members Michael Gatley, MD, and Neil Smith, DO, as well as Lynn Nile, MD, Soad Khalifa, MBCHB, Sylvia Galvez, FNP, PMHNP, Avak A. Howsepian, MD;PhD, and the staff of the Cottage and Faleola services at the Matariki Community Mental Health Centre in Auckland, New Zealand.

Disclaimer: The views expressed in this presentation are those of the presenter and do not reflect the official policy of the VACCHCS or the Department of Veterans Affairs.

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