Psychiatric Annals

CME Article 

Charting the Course of Electroconvulsive Therapy: Where Have We Been and Where Are We Headed?

Peter B. Rosenquist, MD; W. Vaughn McCall, MD, MS; Nagy Youssef, MD

Abstract

Electroconvulsive therapy (ECT) is one of the oldest and best treatments for severe mental illness. A safe and highly effective option for treatment-resistant mood disorders, ECT can be a lifesaving treatment for people suffering from catatonia and acute suicidality. Less recognized are the benefits of ECT in the treatment of primary psychotic disorders, Parkinson's disease, and status epilepticus. Evidence from multisite clinical trials in the past decade shows an evolving standard for the delivery of ECT to achieve and maintain remission and quality of life. Today, the optimal practice of ECT is defined by evidence-based treatment planning, including patient selection, choice of electrode placement and stimulus parameters, augmentation with pharmacotherapy, and the use of continuation/maintenance treatment. Research into biomarkers and neuroplasticity related to ECT response, as well as new investigational methods of delivering ECT, provide a glimpse into the future of this time-tested treatment. [Psychiatr Ann. 2016;46(11):647–651.]

Abstract

Electroconvulsive therapy (ECT) is one of the oldest and best treatments for severe mental illness. A safe and highly effective option for treatment-resistant mood disorders, ECT can be a lifesaving treatment for people suffering from catatonia and acute suicidality. Less recognized are the benefits of ECT in the treatment of primary psychotic disorders, Parkinson's disease, and status epilepticus. Evidence from multisite clinical trials in the past decade shows an evolving standard for the delivery of ECT to achieve and maintain remission and quality of life. Today, the optimal practice of ECT is defined by evidence-based treatment planning, including patient selection, choice of electrode placement and stimulus parameters, augmentation with pharmacotherapy, and the use of continuation/maintenance treatment. Research into biomarkers and neuroplasticity related to ECT response, as well as new investigational methods of delivering ECT, provide a glimpse into the future of this time-tested treatment. [Psychiatr Ann. 2016;46(11):647–651.]

Electroconvulsive therapy (ECT) for treatment of severe mental illness has withstood the test of time despite persistent stigma based upon the perpetuation of an inaccurate and antiquated view of the procedure. Patients and caregivers often ask, “Is shock therapy still being used today?” The answer is a definitive “yes”—but today's ECT is dynamic and steadily improving. In this review, we trace changes in technique emerging from treatment-oriented research through the past several decades. Even as this work has produced demonstrable improvements, there remain many unanswered questions that, when answered, will point the way forward.

Patient Selection and Outcome

Every treatment may be characterized by range of efficacy, durability, and dose-response and dose-toxicity relationships. Patient selection is the first principle of optimization. With a remarkably broad spectrum in range of efficacy, strong evidence supports the use of ECT in both major depressive disorder (MDD) and bipolar disorder.1 Catatonia, now recognized in the Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5)2 as a separate syndrome occurring in conjunction with a number of other manifestations of brain pathology, is one indication for which ECT may be uniquely beneficial.3 Similarly, ECT should be considered a first-line treatment for mood disorders with psychotic features because of its rapid onset and effectiveness.4 Other presentations for which ECT is appropriately elevated in the treatment algorithm include acute/high-risk suicidal ideation and behavior,5 late-life depression,6 and Parkinson-plus syndromes (for which ECT has demonstrated benefits on motor and nonmotor symptoms).7 Although still often seen as a method of last resort, ECT successfully aborts treatment-resistant status epilepticus in up to 80% of reported cases.8

Less recognized are the benefits of ECT in the treatment of primary psychotic disorders as well as disturbances of mood and thought resulting from neurologic or substance-related causes. A curious divergence in the worldwide use of ECT has occurred, with schizophrenia emerging as the primary indication for ECT in Asia, as opposed to mood disorders in the Western world.9

Recent work has demonstrated additive effects of antipsychotic medication therapy when combined with ECT in treatment-resistant schizophrenia.10 Of those dimensions of psychotic disorders currently identified in DSM-5,2 ECT appears to be most beneficial for catatonic, positive, and mood symptoms, and to a lesser extent for cognition, negative symptoms, and thought disorder, although the mechanism of its broad spectrum of effects is less clear.11

Although antidepressant treatment resistance often results in referral for ECT, it should be understood that this may diminish the expectation of efficacy for MDD.12 Nevertheless, patients who have failed to respond to multiple medication trials may be more likely to benefit from ECT compared with another round of medication. The presence of a comorbid personality disorder appears to have a negative influence on the outcome of ECT, as does duration of illness, suggesting that ECT is most beneficial for more acute and/or episodic neuropathological states.13,14 However, ECT practitioners frequently encounter treatment-refractory patients for whom the administration of ECT results in symptomatic improvement, whereupon other forms of treatment, including psychotherapy, become more viable.

The critics of ECT have charged that it is associated with a net loss of health,15 but the literature on quality of life (QOL) and function presents a different picture.16,17 QOL measures dimensions such as freedom from pain, ability to enjoy relationships, and managing one's own life. Patients with MDD have poor QOL compared with ambulatory primary care patients without MDD, and those referred for ECT have even worse QOL.16 ECT confers immediate improvements in mean QOL and function in 80% to 90% of MDD patients, and improvement is sustained for approximately 6 months.16 Importantly, the improvement in QOL is explained by improvements in mood, whereas the patient's cognitive status after ECT does not contribute to the variance in QOL.17 ECT is a safe procedure, but increasing age and preexistent cardiac disease increase the risk of minor and major complications.18

A recent Veterans Affairs (VA) study showed no deaths associated with ECT in any VA hospital between 1999 and 2010.19 Based on the number of treatments given, the authors estimate the mortality rate associated with ECT as less than 1 death per 73,440 treatments, with the most common adverse events reported being injury to the mouth (including dental and tongue injury) and problems related to paralysis.19

Treatment Course

One question that frequently arises with ECT concerns the number of sessions that are required. A standard answer might be 6 to 12 treatments in an “index” acute course administered 2 to 3 times weekly until the patient remits, defined by a rating scale score using a clinician or patient self-rated instrument validated for this purpose.20,21 The use of such measures ensures that patient and provider are cognizant of gradual improvements, which often lag behind global assessments prejudiced by depressive cognitive bias. Speed of response is variable, with some patients noting rapid cessation of suicide ideation or achieving full remission within a few treatments. Longer treatment courses are generally expected to achieve meaningful improvements in symptoms of schizophrenia.

Dosing

One might ask why not optimize treatment by using the highest dosage from the outset of treatment? Like drug treatment, ECT is associated with dose-dependent cognitive side effects, such as postictal impairments in attention, concentration, and deficits in autobiographical memory. These develop during the course of treatment but can often be mitigated by a step-wise approach. Many practitioners have adopted a method of dose titration, thereby identifying an individualized seizure threshold defined by the lowest electrical charge required to initiate a seizure in a particular patient. This forms the basis for dosing subsequent treatment. Typically, bitemporal (BT) and bifrontal (BF) treatment is delivered at 1.5 to 2 times the seizure threshold, whereas right unilateral (RUL) treatment requires 4 to 6 times the seizure threshold to achieve a positive treatment outcome.22

Electrode Placement and Stimulus Characteristics

Initial choice of electrode placement is subject to some interpretation. Compared with RUL and BF, BT ECT is associated with significantly greater risk of cognitive impairment;23,24 yet many ECT practitioners default to BT treatments based upon the perception that it provides a more robust or rapid response. However, the body of evidence in support of RUL ECT suggests that crossover to BT is required in a minority of cases.25

Our understanding of the nature of the ECT stimulus has evolved over time (Figure 1). Although effective at seizure generation, sine wave ECT was definitively shown to be more cognitively impairing and is now considered outdated.24 Modern ECT devices deliver a rectified “square” pulse. The square pulse is more efficient and, therefore, requires less total charge to induce a seizure. Similarly, decreasing the pulse width (from 2 ms to 1 ms) makes ECT more efficient and less likely to produce cognitive impairment. Brief pulses of 0.5 to 1 ms are generally effective and well-tolerated. More recently, “ultra-brief” pulse ECT, defined as less than 0.5 ms (commonly 0.25 to 0.37 ms with current devices), has appeared to be even more efficient and cognitively benign. For unclear reasons, in the initial study of ultra-brief stimuli (ultra-brief BT ECT) it was less effective than all other arms in the study (brief BT, brief RUL, and ultra-brief RUL).26 Although confirming the relative cognitive advantage of ultra-brief RUL, other studies have produced conflicting results about its efficacy.24 Some studies show lower rates of remission or prolonged treatment course, but efficacy appears to be comparable at a higher stimulus intensity (8 times seizure threshold).27


            Electroconvulsive therapy waveforms. ECT, electroconvulsive therapy; FEAST, focal electrically administered seizure therapy.

Figure 1.

Electroconvulsive therapy waveforms. ECT, electroconvulsive therapy; FEAST, focal electrically administered seizure therapy.

Coordination with Other Therapies to Achieve and Maintain Remission

ECT is generally not employed as monotherapy. One important discovery was that the remission rate for MDD is improved with concomitant antidepressant medication therapy.28 ECT plus placebo resulted in a remission rate of only 49%, whereas the addition of venlafaxine or nortriptyline improved this to 62% and 64%, respectively.28 Lack of antidepressant treatment after remission with ECT results in relapse for 90% of patients, whereas maintenance pharmacotherapy with antidepressant alone is only marginally effective (61% relapse within 6 months).29 Augmentation of antidepressants with lithium is the gold standard for pharmacotherapy after ECT, reducing relapse rates to anywhere from 2% to 40%.29,30

There is emerging evidence that the addition of maintenance ECT might be more helpful in treatment-resistant cases to maximize chances of sustaining remission.31 In a large randomized trial, maintenance ECT alone was demonstrated to be equivalent to lithium plus nortriptyline (sustained remission rate of 46%).32 Additional studies have shown that maintenance ECT plus pharmacotherapy is more effective than pharmacotherapy alone at 1-year and 2-year follow-up appointments.33

Biomarkers

There are no widely accepted biomarkers of clinical response, although a number of studies have shown that electroencephalographic measures of induced seizure duration or morphology are modest predictors.34 These “seizure quality” measures may be identified by visual inspection or by algorithms built into the ECT device. When the patient is improving as expected, such measures are of little consequence; however, when the patient is slow to respond it may provide additional impetus to increase stimulus dose, change electrode placement, or withdraw concomitant medications with potential to affect the seizure.

Preliminary studies in humans and animals show a favorable effect of ECT in inducing neurogenesis and neuroplasticity.35 One study demonstrated increased hippocampal and amygdala volumes after ECT, which correlated with the improved clinical response.36 These data have attracted attention to the possible role of adult neurogenesis in the antidepressant effect of pharmacological agents.35

The Future of ECT

The future of ECT depends on continued refinement of the technique to minimize side-effect burden while maintaining effectiveness. Two lines of innovation are currently being investigated with the goal of diminishing side effects by making seizure activity more focal—magnetic seizure therapy (MST) and focal electrically administered seizure therapy (FEAST). MST capitalizes on the fact that the skull is transparent to the magnetic field and easily overcomes scalp/skull impedance. The magnetic field is transferred in the brain by eddy currents (Faraday's law of induction) with more focality.37 FEAST uses a unidirectional pulsed stimulus along with asymmetrically sized electrodes to deliver a focal current to the target areas believed to be most responsible for depression, including the right orbitofrontal cortex.38

Preliminary research suggests that FEAST and MST are cognition-sparing compared to traditional ECT, but they have yet to demonstrate comparable efficacy.39 MST presents unique engineering challenges because of inefficient energy transfer to brain tissue, requiring excessively high-powered devices to generate a seizure. Also, the penetration in the brain is superficial, with a depth of only 2 to 4 cm below the coil.40

Although we envision that ECT will remain the backbone of treatment for severe and treatment-resistant psychiatric illness, mounting experience with alternative brain-stimulation modalities such as repetitive transcranial magnetic stimulation and transcranial direct current stimulation may well provide novel insights to guide the further development of this time-tested treatment.

References

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Authors

Peter B. Rosenquist, MD, is a Professor. W. Vaughn McCall, MD, MS, is a Professor. Nagy Youssef, MD, is an Associate Professor. All authors are affiliated with the Department of Psychiatry and Health Behavior, Medical College of Georgia, Augusta University.

Address correspondence to Peter B. Rosenquist, MD, Department of Psychiatry and Health Behavior, Medical College of Georgia, Augusta University, 997 St. Sebastian Way, Augusta, GA 30912; email: prosenquist@augusta.edu.

Disclosure: W. Vaughn McCall receives research support from Merck & Co. and MECTA Corporation; has been a consultant for Merck & Co., Luitpold Pharmaceuticals, and Aetna Insurance; is on the speakers bureau for CME Outfitters; and receives royalties from Wolters Kluwer Health publishing. Nagy Youssef receives research support from the US Department of Veterans Affairs and August Biomedical Research; and has received CME honoraria from the Georgia Department of Behavioral Health and Developmental Disabilities. The remaining author has no relevant financial relationships to disclose.

10.3928/00485713-20160927-01

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