Electroconvulsive Therapy - Time to Bring It Out of the Shadows

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Electroconvulsive Therapy:
Time to Bring It Out of the Shadows

by Richard M. Glass, MD

Electroconvulsive therapy (ECT) is one of the most controversial treatments in all of medicine. There are a number of reasons for this. The discovery in the 1930s that inducing a series of generalized seizures, initially with chemicals,¹ later with electric current,² could cause the recovery of patients with severe and previously untreatable mental disorders produced a wave of enthusiasm that eventually led to a period of indiscriminate use and misuse in the middle decades of the 20th century.³^{, 4} This period of abuse created, perhaps deservedly at that time, a bad reputation for an effective treatment modality. That reputation was enhanced by the immediate adverse effects of bitten tongues and even fractured bones and teeth caused by the induction of generalized seizures, and the painful effects of electroshocks administered without anesthesia when they did not successfully induce a seizure with loss of consciousness.

The 1975 movie One Flew Over the Cuckoo's Nest contributed to an erroneous view of ECT as a punitive, painful, and assaultive procedure used by authorities to control inconvenient creativity. That view has been associated with attempts to regulate, or even eliminate, the use of ECT through legislation in a number of jurisdictions, and public fears and distrust about the use of ECT have persisted. The best response to such concerns on the part of physicians is to be aware of the facts about current use of ECT, including its efficacy and possible adverse effects, so they can respond to questions from patients, families, and the public.

The indications, possible adverse effects, and current recommendations for treatment procedures have been summarized in a task force report just published by the American Psychiatric Association Committee on Electroconvulsive Therapy.⁵ An effective and safe treatment for severe major depression, ECT has had response rates reported in the range of 80% to 90% as a first-line treatment, and in the range of 50% to 60% for patients who have not responded to 1 or more trials of treatment with antidepressant drugs.⁵(p10) Electroconvulsive therapy may also be seriously considered as treatment for patients with acute mania, and for patients with schizophrenia who have not responded to adequate trials of antipsychotic medications.⁵(pp14-19) As currently practiced, ECT involves the use of informed consent, ultra-brief general anesthesia and muscle relaxants (thus attenuating motor seizure activity) with appropriate airway management, and use of ECT devices to provide adequate ictal responses. Most patients in the United States receive 3 treatments per week, and a course of ECT for major depression generally consists of 6 to 12 treatments, with the course ended or tapered as soon as maximum response has been reached. This usually occurs more quickly than the 4 to 6 weeks required for an adequate trial of an antidepressant drug.

There continues to be some controversy about the use of right unilateral or bilateral electrode placement, with right unilateral ECT causing less cognitive adverse effects, but bilateral ECT often viewed as being more effective. A recent randomized controlled trial ⁶ showed that right unilateral ECT at high dosage was as effective as bilateral ECT in many patients and caused less impairment on several measures of anterograde and retrograde memory.

The issue of cognitive adverse effects from ECT is central to its reputation for harm and requires careful consideration to separate facts from myths. Studies of this issue have been reviewed and summarized by the American Psychiatric Association Committee on Electroconvulsive Therapy.⁵(pp66-73) Patients experience a variable but usually brief period of disorientation (postictal confusion) immediately after seizure induction. Electroconvulsive therapy also typically results in retrograde amnesia,⁷^{, 8} greatest immediately after the course of treatment and for events that occurred temporally close to the treatment. The extent of the retrograde amnesia usually decreases substantially with time, but many patients have persistent loss of memory for some events that occurred in the interval starting several months before and extending to several weeks after their ECT course.

Anterograde amnesia, characterized by rapid forgetting of learned information, also may occur during and immediately following ECT but resolves within a few weeks.⁵(p70) Importantly, there is no objective evidence that ECT has any long-term effect on the capacity to learn and retain new information.

Assessment of cognitive effects from ECT is complicated by the cognitive impairments associated with the mental disorders being treated. For example, patients with severe depression may have substantial impairments in cognitive function, and patients with schizophrenia or other psychotic disorders almost always do. The extent of cognitive adverse effects immediately following ECT is also influenced by treatment parameters, such as bilateral vs unilateral electrode placement, the electrical dosage relative to seizure threshold, and the number and spacing of treatments.

The occurrence and characteristics of memory loss following ECT must be part of informed consent for it,⁵(pp319-322) but it is also important to recognize that there is no evidence that ECT results in lasting impairments of abstract reasoning, creativity, or skill acquisition or retention.⁵(p70) There is also no evidence that ECT causes structural damage to the brain.⁹^{, 10}

In stark contrast to the results of objective studies of the cognitive effects of ECT are the reports of a minority of patients who believe they have developed devastating cognitive consequences from ECT.⁴ A study of patients with long-term complaints about the effects of ECT found few objective neuropsychologic differences, but marked differences in psychopathology from control groups.¹¹ Some patients with such complaints may have experienced cognitive impairment as a result of the mental illness for which they received ECT. Nevertheless, even though such reports are rare in comparison with the large number of patients who have received and benefited from ECT, they merit further study. The occurrence of these rare complaints should also be acknowledged in the informed consent process.

Another source of public fears and distrust about ECT is that, on the face of it, producing convulsions with electric current seems like a strange way to treat illness. The initial use of convulsive therapy was based on an erroneous impression of a "biological antagonism" between severe psychiatric disorders and epilepsy.³ As is true for other treatments for mental disorders, there is now an impressive database regarding indications, efficacy, and adverse effects, but little definitive information about mechanisms of action. This reflects the paucity of reliable knowledge about the pathophysiology and etiology of mental disorders and the need for further research in those areas.

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One issue regarding ECT that has been in need of careful research is the problem of relapse following a successful course of treatment for major depression. Clinical experience and naturalistic studies suggest that relapse rates are high after a successful course of ECT,¹² so prevention of relapse following ECT has been a clinical problem in need of systematic study. The need for such research is highlighted by the increasing evidence that major depression is usually a recurrent or chronic disease and that maintenance treatment with antidepressant drugs, psychotherapy, or both, is necessary to prevent relapse after successful treatment of an acute episode.¹³

In this issue of THE JOURNAL, Sackeim et al¹² report the results of a multicenter, randomized controlled trial that addressed the important clinical problem of preventing relapse following a course of ECT. Of 290 patients with major depression who received a course of ECT, 159 (55%) met stringent criteria for remission and 84 of the remitted patients then gave their informed consent to be randomly assigned to receive continuation therapy with the tricyclic antidepressant nortriptyline hydrochloride, the combination of nortriptyline and lithium carbonate, or placebo. The absence of prior reliable information about the efficacy of pharmacotherapy to prevent relapse following ECT justified, indeed required, use of a placebo control group. Therapeutic blood levels were targeted for nortriptyline and lithium, and all study patients were evaluated carefully for evidence of relapse. Patients who relapsed were switched to alternate treatments based on clinical judgments.

About half of the patients entering randomized continuation treatment had medication-resistant depressive episodes before they responded to ECT, most of them having not responded to selective serotonin reuptake inhibitor antidepressant drugs. Nortriptyline and lithium were chosen as the continuation treatment medications to decrease the chance that patients would have already not responded to a drug in the same class, and in view of previous evidence that tricyclic antidepressants may be more effective for severe depression and that the tricyclic-lithium combination can be effective in medication-resistant major depression.¹² These 2 drugs also have the advantage of having well-established therapeutic blood level parameters.

The main result was that the nortriptyline-lithium combination had a marked advantage in time to relapse, with 6-month relapse rates of 84% for placebo, 60% for nortriptyline alone, and 39% for nortriptyline plus lithium. Patients who had medication-resistant index episodes and those with higher depression rating scores at the start of continuation treatment had higher relapse rates. It is important to view these results in the context of the current use of ECT for patients with severe and often medication-resistant depressive disorders. Although major depression can often be treated successfully, there is a great need for progress in developing treatments that can achieve and maintain recovery for patients with depressive disorders that do not respond readily to currently available treatments.

These results suggest that virtually all patients who respond to ECT for an episode of depression will require continuation antidepressant treatment to decrease the likelihood of relapse, a finding that comports with the evidence for drug treatments,¹³ and most patients will probably require maintenance treatment of some kind to prevent reoccurrences.

As Sackeim et al¹² point out, even though the nortriptyline-lithium combination led to substantially lower relapse rates than placebo or nortriptyline alone, a relapse rate of 39% in 6 months is still far too high. These investigators suggest that tapering ECT for several weeks after recovery, rather than stopping it at that point as is the usual practice, and starting antidepressant medication during, rather than after, the course of ECT should be tested to see if those strategies decrease relapse rates. Providing better antidepressant coverage in the first several weeks after a course of ECT does appear to be important, since all but 1 of the patients who relapsed in the nortriptyline-lithium group did so within the first 5 weeks. The use of ECT for continuation or maintenance treatment,⁵(pp208-212) given at considerably less frequent intervals than for acute treatment, may also be considered, particularly for patients who have responded well to ECT but who have relapsed on other antidepressant treatments.

All considerations about ECT must include recognition of the suffering and devastating consequences caused by major depression, a disease with a mortality rate as high as 15% (mainly due to suicide) and major adverse effects on other medical disorders.¹³ A recent study of premature mortality and disability ¹⁴ ranked major depression as the fourth leading cause of worldwide disease burden. The results of ECT in treating severe depression are among the most positive treatment effects in all of medicine. Yet this effective treatment too often remains in the shadows of stigma and fear. The study reported by Sackeim et al¹² is a good example of the growing scientific database that can usefully inform clinical decisions about this treatment. For the sake of the many patients with major depression and their families, it is time to bring ECT out of the shadows.

This editorial appeared in the March 14, 2001 issue of the Journal of the American Medical Association.

Author/Article Information

Author Affiliation: Dr Glass is Deputy Editor, JAMA.

Editorials represent the opinions of the authors and THE JOURNAL and not those of the American Medical Association.

Acknowledgment: I thank Larry S.Goldman, MD, and Francis McMahon, MD, for helpful comments on a draft of this editorial.

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Electroconvulsive Therapy: Time to Bring It Out of the Shadows

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Electroconvulsive Therapy:
Time to Bring It Out of the Shadows