Convulsive therapy: a review of the first 55 years

Journal of Affective Disorders 63 (2001) 1–15 www.elsevier.com / locate / jad

Millenial article

Convulsive therapy: a review of the first 55 years Max Fink a

a,b,c ,

*

Departments of Psychiatry and Neurology, Long Island Jewish–Hillside Medical Center, Glen Oaks, Long Island, NY 11004, USA b Department of Psychiatry and Neurology, School of Medicine, State University of New York, Stony Brook, NY, USA c Departments of Psychiatry, Albert Einstein College of Medicine, New York, NY, USA Received 30 June 2000; accepted 15 November 2000

Abstract Convulsive therapy was introduced to psychiatric practice in 1934. It was widely hailed as an effective treatment for schizophrenia and quickly recognized as equally effective for the affective disorders. Like other somatic treatments, it was replaced by psychotropic drugs introduced in the 1950s and 1960s. But two decades later, ECT was recalled to treat pharmacotherapy-resistant cases. Avid searches to optimize seizure induction and treatment courses, to reduce risks and fears, to broaden the indications for its use, and to understand its mechanism of action followed. Unlike other medical treatments, however, these searches were severely impeded by a vigorous antipsychiatry movement among the public and within the profession. ECT is effective in the treatment of patients with major depression, delusional depression, bipolar disorder, schizophrenia, catatonia, neuroleptic malignant syndrome, and parkinsonism, and this breadth of action is both remarkable and unique. ECT is a safe treatment. No age or systemic condition bars its use. Its major limitations are the high relapse rates and the occasional profound effects on memory and recall that mar its success. Experiments to sustain its benefits with medications and with continuation ECT are underway. Its mode of action remains a mystery and this puzzle is an unappreciated challenge. The full impact of this intervention is yet to be felt.  2001 Elsevier Science B.V. All rights reserved. Keywords: Convulsive therapy; History; Experience

1. Origin of convulsive therapy 1 At 10:30 on the morning of January 24, 1934, the

Hungarian neuropsychiatrist Ladislas Meduna approached the bed of a 30-year-old Budapest laborer who appeared lifeless. Zoltan had hardly spoken or

*P.O. Box 457, St. James, NY 11780, USA. Tel.: 1 1-631-862-6651; fax: 1 1-631-862-8604. E-mail address: [email protected] (M. Fink). 1 This essay follows my earlier surveys of the history of convulsive therapy. My first report was published in the textbook Convulsive Therapy: Theory and Practice (Fink, 1979). Meduna and the origins of convulsive therapy appeared on the 50th anniversary of its origin (Fink, 1984). In 1985, I published Ladislas Meduna’s autobiography (Meduna, 1985) in the inaugural issue of the journal Convulsive Therapy, with a historical review (Fink, 1985). The introduction of electroconvulsive therapy in 1938 was described in a special issue of Convulsive Therapy (1988; 4:1–87). The Impact of the anti- psychiatry movement on the revival of ECT in the US discussed both public and professional actions against ECT (Fink, 1991). It was expanded in a later report (Fink, 1997c). A detailed history intended for the laity is found in Chapters 10–12 in Electroshock: Restoring the Mind (Fink, 1999) and in an article in the American Scientist (Fink, 2000). While other authors have published essays on different aspects of the unfolding history of this remarkable treatment, no detailed history has been published. 0165-0327 / 01 / $ – see front matter  2001 Elsevier Science B.V. All rights reserved. PII: S0165-0327( 00 )00367-0

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cared for himself for more than 4 years; his mental condition of catatonic schizophrenia was considered hopeless. No remedy was available and none looked for, as the doctors believed the illness to be an immutable genetic fault, laid down at the moment of conception. Meduna injected an oily extract of camphor into the patient’s right buttock. Soon the patient’s heart raced, sweat rose on his brow, and he became increasingly fearful, and after 45 minutes, his eyes suddenly closed, his jaw clenched, breathing stopped, and he lost consciousness. With a deep and noisy sigh, his arms and legs extended, he convulsed, and his bed thumped rhythmically as the attendants caught him as he was about to roll to the floor. His skin became ashen, and he wet the bed. As suddenly as the spasm started, it ended. His eyes opened and a pink color slowly returned to his cheeks. Zoltan continued to stare and was as speechless as before. He had survived an induced grand-mal epileptic fit. Meduna described the occasion. ‘During the period of observation I was able to maintain my composure and to make the necessary examinations with apparent calm and a detached manner. I examined his reflexes, the pupils of his eyes, and was able to dictate my observations to the doctors and nurses around me; but when the attack was over and the patient recovered his consciousness, my legs suddenly gave out. My body began to tremble, a profuse sweat drenched me, and, as I later heard, my face was ashen gray.’ 2 How often should seizures be induced? Meduna adopted the schedule used in the malarial fever treatment of neurosyphilis.3 He injected camphor at 3–4-day intervals, and 2 days after the fifth seizure, Zoltan awakened, looked about, got out of bed, asked where he was, and requested breakfast. He did not believe that he had been in hospital for 4 years,

and knew nothing of the intervening history. Later that day, he again relapsed to stupor. After each of the next seizures, Zoltan remained alert and interested for longer and longer periods, until after the eighth injection he left the hospital to return to his home and to work. His mental condition was relieved. Five years later, when Meduna left Europe for America, Zoltan was well and working. Meduna treated five additional schizophrenic patients and each recovered. Such an experience was remarkable but especially so since the medical profession believed that the disease was relentlessly progressive and hopeless.4 Camphor injections were painful and the seizure developed after an agonizing and frightening delay of many minutes. By contrast, Metrazol (pentylenetetrazol) injected intravenously induced a fit quickly. Within a minute, the patient’s thoughts raced, his heart beat rapidly, terror filled the mind, and consciousness was lost. After a few minutes of seizing, the patient slowly re-awakened, his muscles, back, and head ached, and often his tongue and lips were bleeding. Memory of recent events was erased. Despite the risks and terrors, and the need for repeated frequent injections to achieve a benefit, within two years Metrazol seizure therapy was widely adopted throughout the world. Its success changed public and professional attitudes toward mental illness from one of hopeless resignation to optimism that relief of a mental illness was possible. Why did Meduna seek to induce seizures to relieve dementia praecox? The success of malarial therapy for neurosyphilis encouraged the model of biological antagonisms as a treatment strategy in medicine. Reports that dementia praecox was relieved when patients developed an epileptic disorder (as after head trauma or meningitis), and the low

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Meduna (1985). 3 In 1917, Professor Julius Wagner-Jauregg of the University of Vienna reported the benefits of malarial fevers in six of nine patients with neurosyphilis (dementia paralytica). The benefit was considered so remarkable that he was awarded the Nobel Prize for Medicine in 1928. The treatment of patients with one illness by inducing another became a paradigm in developing psychiatric treatments, leading to prolonged sleep therapy (1922), insulin coma (1933), convulsive therapy (1934), and leucotomy (1935).

Meduna followed the idea of an antagonism between dementia praecox and epilepsy while working at the Hungarian Psychiatric Research Institute in Budapest. Fearing, however, that he would be prevented from doing clinical trials at the Institute by the Director’s belief in the immutability of dementia praecox, Meduna moved the clinical trials to a state psychiatric hospital outside the city. When he reported his findings to the Institute Director, he was severely criticized, not for the experiments, but for the belief that he could alter the psychotic process (Meduna, 1935a,b, 1937, 1985).

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incidence of psychosis among patients with unremitting epilepsy led clinicians to view epilepsy and dementia praecox as antagonistic disorders. Meduna, a neuropathologist, had studied the concentration of the brain cells known as glia in autopsied patients with various disorders. Glial concentrations were much higher among those who had an epileptic disorder and much lower among those with dementia praecox than in those with systemic disorders.5 Although the functions of glia were unknown, Meduna thought it reasonable to increase glial concentrations among those with dementia praecox. He sought a safe, seizure-producing chemical and came upon camphor first, and Metrazol after a few months. Injections of these medicines induced seizures and the animals survived.

2. Search for optimal method of seizure induction Metrazol seizures were widely adopted, but the terrors induced by each injection led patients to fear and to reject the treatment. A better induction method was sorely needed and experiments with electrical inductions were undertaken in Rome by Cerletti and Bini.6 At first, electrodes were placed in the mouth and the anus of experimental animals, and while seizures were induced, animals died, probably from cardiac arrest. Trials with electrodes placed on the animal’s temples showed that seizures were immediate. On May 15, 1938, a seizure was successfully elicited with electricity in a 39-year-old delirious manic man. Unmodified alternating current at 220 V was used in the first treatments, with the currents applied for one second. Many different forms, frequencies, amplitudes, and pulse-widths of electric currents were tested over the next decade, leading to the brief-pulse squarewave forms of currents used in present-day devices. Further optimization is in progress, mainly by seek5

In contrast to the fears that repeated seizures would damage brain tissues, recent studies of seizures finds an increase in neurogenesis — the number of neurons increase with repeated seizures (Madsen et al., 2000). 6 Bini (1938, 1995), Cerletti (1950, 1956).

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ing ever briefer pulse widths, but such experiments promise only minimal incremental benefits in treatment efficiency over present current forms.7 Is the passage of electric currents alone, without the development of seizures, of clinical benefit? When lidocaine modified the duration and the characteristics of the seizure, the incomplete and partial seizures were clinically ineffective.8 Nor was a benefit found when subconvulsive currents were used.9 Two decades later, the British Medical Council supported six convulsive–subconvulsive treatment studies that again found subconvulsive treatments to have little clinical benefit. These studies showed that the induction of a grand mal seizure was essential to ECT’s therapeutic service. Not every grand mal seizure elicits equal clinical benefit. The outcome is affected by the path of the currents. To increase the efficacy of RUL and to approximate the efficacy of BT, energies to stimulate seizures must be at least six times the measured seizure threshold.10 In RUL, the maximum concentration of energies is across the motor strip, eliciting seizures at lower energies than when currents are directed through the brain stem by either BL or bifrontal (BF) electrodes.11 These observations suggest that the benefits of ECT come from the stimula-

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Fink (1979), Abrams (1997). Ottosson (1960). 9 Ulett et al. (1956), Fink and Kahn (1957), Palmer (1981), Abrams (1997). 10 In unilateral electrode placements (RUL), one electrode is placed over the right (non-dominant) temple and the second placed over the posterior vertex on the same side. RUL was first used in 1971, and within a few years, had been widely tested (d’Elia and Raotma, 1975; Fink, 1979; Abrams, 1997). The path of currents affects clinical outcome (Sackeim et al., 1987, 1993) and RUL treatments are less effective than BT (Sackeim et al., 1987, 1993, 2000; McCall et al., 2000). 11 Current flow requires two electrodes to be applied to the head to stimulate a seizure. The customary placement for bilateral ECT is with electrodes over the two temples, about 1 to 2 inches from the outer canthus of the eye. Interest has recently been shown in bifrontal placement — either symmetric with the two electrodes on the forehead about 1 inch above the outer canthus, or an asymmetric placement with the right electrode over the temple and the left on the forehead over the left outer canthus (Lawson et al., 1990; Letemendia et al., 1993; Manly and Swartz, 1994; Bailine et al., 2000). 8

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tion of centrencephalic structures, probably the midline hypothalamic–pituitary system.12 Non-electrical methods of seizure induction were tried. Photic stimulation with low doses of Metrazol were effective but were difficult to apply. Seizures induced by the inhalant flurothyl were as effective as ECT, with the same effects on cognition.13 The induction of a seizure by an inhalant, however, was more cumbersome and less reliable than ECT, and it was discarded. Fears of electricity led Austrian authors to propose isoflurane anesthesia as an alternative. Patients were anesthetized on the same weekly schedule as ECT, with the aim that the electroencephalogram (EEG) be recorded as ‘flat’ (isoelectric) for up to 1 h during each session. The first reports were optimistic, but replications failed to show benefit. The risks and costs of isoflurane were greater, the benefits limited, and the method was discarded.14 Among recent methods of non-electric stimulation are rapid transcranial magnetic stimulation [rTMS] and vagal nerve stimulation (VNS). Both methods have been proposed as substitutes for the seizures of ECT but the proponents have yet to establish effective procedures. The most recent application of rTMS is to induce grand mal seizures, and the first such treatment was explored in Switzerland in April, 2000.15

3. Search to optimize the treatment course The search to improve the efficacy and safety of each treatment has been accompanied by a diligent search for an optimal course of treatment, one that 12 For a discussion of the elements of modern ECT that are deemed to be in the therapeutic chain, see subsequent section on theories. Also Fink (1990, 1999, 2000). 13 Fink (1979). 14 Langer et al. (1985), Greenberg et al. (1987). 15 ¨ At meetings in Chicago in May, 2000, Dr Thomas Schlapfer (Psychiatric Neuroimaging Group, University of Bern, Switzerland) showed pictures of the induction of a grand mal seizure in a female patient using rTMS. The seizure was indistinguishable in form to that produced in ECT. The depressed patient received four rTMS inductions followed by eight ECT, with improvement in mood (personal communication, May 14, 2000). Such an induction appears as complex as photic stimulation or flurothyl inhalation. The VNS digression does not, as yet, have seizure induction as its goal.

would be effective with the fewest seizures and with benefits that would persist. Meduna tested treatments on 2- to 3-day intervals, and this frequency is used today. Some authors sought to give ‘a course’ of up to eight treatments in one day, under one anesthesia. Labeled ‘multiple monitored ECT’, benefits were only occasionally seen, and equally often, the patients sustained a severe impairment of memory.16 A well-controlled study compared the benefits of two treatments a week with three finding the courses to be equally effective. The antidepressant changes occurred earlier and the cognitive effects were more severe for treatments at the shorter intervals, but the benefits and side-effects were indistinguishable after 2 weeks.17 A major impediment to ECT has been the high relapse rate. When ECT was recalled to use, it was with much public and professional criticism and with fears that repeated seizures would cause brain damage. Electrotherapists sought to achieve and sustain the benefits with the fewest number of seizures. But short courses of ECT are no more persistent in their benefits than are short courses of medications. Some thought that medications would sustain the benefits of ECT even if they had not produced a remission, but such optimism was unrealistic. Continuation ECT — treatments at biweekly or monthly intervals over 4–6 months — is now under intensive study as a way to sustain the treatment’s benefits.18 We no longer recommend a short course of ECT, even when its benefits are well defined, without offering continuation ECT. The data are sparse, however, and our search for effective continuation tactics are in the forefront of present-day research. Because we were unsure of the interaction of the new psychotropic agents and ECT, most physicians curtailed the use of medicines during the ECT 16

Maletzky (1981), Abrams et al. (1973), American Psychiatric Association (1990). 17 Lerer et al. (1995). 18 A four-hospital consortium is in the midst of a large study of patients with unipolar depression testing the merits of continuation ECT. After treatment with bilateral ECT and achieving single digit scores and greater than 60% reduction in the Hamilton Depression Scale scores, patients are randomly assigned to either continuation ECT compared to continuation lithium and nortriptyline. Sites are Long Island Jewish Hillside Hospital (NY), Mayo Clinic (MI), Medical University of South Carolina (SC), and the University of Texas in Dallas.

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course.19 Reviews of the interactions of ECT and psychotropic drugs find some interactions to be synergistic (neuroleptics), some antagonistic (benzodiazepines, anticonvulsants), and some eliciting confusional syndromes (lithium). We are unsure of the interaction of ECT and antidepressants, so we most often curtail their use. Studies underway suggest that the clinical benefits of antidepressant drugs may, like the effects of antipsychotic drugs, be augmented by ECT.

4. Search to reduce risks and fears In its early years, ECT was associated with fear and panic, fractures, headache, bitten tongues, and memory defects. Improvements in techniques have minimized these risks.

4.1. Fracture and panic Fractures of the spine, long bones, and jaw led to a search for a muscle paralytic agent that was transient in its effect. Curare was the first effective paralytic agent, but this plant extract was unstable, giving variable protection.20 Succinylcholine, discovered in 1952, was a better alternative.21 It is rapidly effective and the duration of its effect is short. But the patient’s awareness of paralyzed respiration required an agent to produce amnesia for the period of muscular paralysis. A barbiturate anesthetic, now most often methohexital or thiopental, are in routine use.22 To prevent damage to teeth and jaw, a disposable bite-bloc is used, one that is similar to those used in body contact sports. For patients with loose or missing teeth or with dentures, special plastic bite-blocs are made for individual patients to assure a proper fit. The fear and panic induced by the delay in the induction of the seizure had been largely dissipated by the immediacy of the seizure. Barbiturates before

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Fink (1979, 1994), Abrams (1997), Kellner (1993). Bennett (1941, 1972). 21 Holmberg and Thesleff (1952). 22 Benzodiazepines raise seizure thresholds sufficiently to impair treatment efficacy and these are no longer recommended. Accepted alternative muscle relaxants include atracurium and mivacurium; alternative anesthetics are ketamine and etomidate. 20

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the induction of a seizure also reduce the threatening aspects of the treatment.23 Detailed discussions during the consent process and viewing videotapes describing the treatment lessen anticipated anxiety.24

4.2. Brain damage The public’s fear of electricity and its use in state-mandated executions led to intense concerns that ECT will induce persistent brain damage. This fear is not supported by clinical experience or by neuropsychological tests, EEG, and brain imaging in humans or by neuropathological studies in animals. These studies do not find persistent effects on brain structures, even after extensive courses of ECT.25 Indeed, recent studies report an increase in new neuron growth (neurogenesis) with electroconvulsive seizures, holding promise for an unusual, potentially beneficial, effect of seizures on brain cell growth.26

4.3. Memory Once the problem of fractures and panic were eliminated, concerns about the immediate and longterm effects on memory dominated ECT research.27

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The images of seizures in modern films encourage terror and fear that patients will be forced to an unwelcome and painful treatment. Such films as the Snakepit (1948) and One Flew Over the Cuckoo’s Nest (1975) set an anti-ECT tone at a time when Hollywood films portrayed Freudian psychiatrists as paternalistic and avuncular humanists (Gabbard and Gabbard, 1987). 24 Educational videotapes are produced by Fink (1986b), Grunhaus (1988), Solvay Pharmaceuticals (1997). An educational web-site was developed by Fink (1999): http: / / www.electroshock.org 25 Devanand et al. (1994), Abrams (1997). 26 Madsen et al. (2000). 27 The complaint about the memory effects is often stated as the basis for state governments to restrict the use of ECT based on testimonials by persons who received ECT and who blame persistent difficulties in living on their treatment. Malpractice suits have argued that the subjects were plagued by obsessive thoughts that important memories were lost. Such was the basis for the complaints by Marilyn Rice and Linda Andre, two women who organized and managed a volunteer anti-psychiatry group, and at least three malpractice cases by nurses. A similar experience is described by Donahue (2000). The effects of ECT on memory have received extensive study. See Abrams (1997), Calev (1994), Calev et al. (1991), Fink (1979, 1999), Lerer et al. (1995), Sackeim (1992, 2000), and Sackeim et al. (1993).

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This concern became critical in the US in the early 1970s, when ECT was re-introduced and the antipsychiatry movements were able to charge that ECT blotted out all memories and made the patients virtual zombies and automatons. The latter terms were applied to the patients after lobotomy and the confusion that ECT was the same as lobotomy severely impeded its use. As a consequence, the major focus of research has been to minimize the effects on memory. Continuous oxygenation eliminated the cyanosis and severe cognitive defects that marked unmodified treatments.28 Electrode placement over the non-dominant hemisphere alone elicited seizures by directly stimulating the motor strip. By avoiding currents directed to memory centers, the effects on memory are minimized. But the efficacy of such induction of treatments is considerably less than seizures induced by currents directed to the brain’s midline structures, particularly the hypothalamus and pituitary.29 To approximate the efficacy of bilateral electrode placement, investigators find it necessary administer treatments with energies set at five to eight times the seizure threshold. When such high energies are applied, the memory effects of RUL increase markedly. The proponents of these methods argue that the long term benefits in memory are sufficient to

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Holmberg (1953a,b). Two reports present the latest data from the psychologist Harold Sackeim. One report claims equivalent efficacy for BT ECT (2.5 3 ST) and RUL (6 3 ST). But the sample sizes are 20 patients each, clearly inadequate for statistical interpretation (Sackeim et al., 2000). A 2-month follow-up showed greater deficits in two of many memory tests for the BT treated patients compared to the RUL treated patients. In a second report, the benefits for RUL were directly related to the strength of stimulus above threshold. The memory tests were done immediately after treatment, and the effects on memory were proportional to the strength of stimulus (McCall et al., 2000). The sample sizes are inadequate to support a firm conclusion. While we have learned much to improve the efficacy of RUL ECT, the present arguments bring practitioners to a dilemma. They are asked to select an inefficient and complex form of treatment (RUL at 6 3 measured ST) with a 20% or greater loss of efficacy and lesser immediate effects on memory, or the more efficient BL or BF treatments with energies just above seizure threshold, with more immediate effects on memory that are usually, but not always, gone with recovery from the illness. 29

warrant the routine use of RUL at six times the energy of the measured seizure threshold.30 Patients do lose the memory of personal events that occurred during the period of illness and the period of treatment. The transient confusion after each seizure heightens patient and family concerns, and re-enforces the fears of memory loss. But for almost all patients, the confusion lifts within a few weeks of the last treatment. For the patients who recover from their illness, they function better than they did during their illness, and this relief makes up for what memories were lost. Some patients complain that their memories never fully return, that they have gaps in their recollection of personal history, and that memories related to work are hampered. These patients sense an estrangement even though they carry on their normal daily activities, and obsess about their losses. They are distressed at not being able to recall the details of events that their friends can. Such losses are rare, but are the basis for much of the anti-ECT feelings expressed by the public, the profession, and in the acts of state legislatures limiting the availability of the treatment.31

4.4. Contraindications We have developed the technical skills to treat patients with severe medical illnesses that were once thought ‘of high risk’ for ECT. So much so, that we no longer consider systemic disease to preclude its use.32 Nonetheless, ECT in patients with life-threat-

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ECT devices in the US are limited by FDA rules to an output no greater than approximately 500 mC. For those patients whose seizure threshold is measured greater than 100 mC, the devices cannot deliver energies to meet the 6 3 ST suggested standard. Approximately 20% of patients have seizure thresholds higher than 100 mC and cannot be effectively treated by this method. 31 Memoirs of the effects of ECT on memory are published by A Practicing Psychiatrist (1965), Endler (1982), Manning (1994), and Donahue (2000). These present more accurate pictures of the impact of ECT than the frenzied rhetoric of the anti-psychiatry movement. 32 Abrams (1989, 1997), American Psychiatric Association (1990).

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ening medical conditions does require special attention in their treatment by experienced practitioners.33

5. Search to broaden indications The ease of administration of ECT and its success in relieving dementia praecox led to its extended use in patients with other mental illnesses. By 1940, ECT had been found effective in relieving depressed mood, agitation, and paranoid ideation of involutional melancholia. The death rate was materially reduced. By the mid-1940s, ECT was used to treat a broad spectrum of mental illnesses regardless of the specific mental symptoms, their severity, duration, or associated systemic disorders. None thought it remarkable that ECT was so broadly effective across so many diagnostic classes.34 In such an optimistic climate, ECT was applied in patients seeking treatment for homosexuality, drug addiction, alcoholism, phobia, and conversion reactions. The failures in these cases led to complaints that patients were abused by ECT practitioners, a complaint that still darkens their image today. When antidepressant medicines appeared in the 1950s, their efficacy was compared to that of ECT. Both proved effective. The ease of use of the medicines, not superior efficacy, led doctors to

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discard ECT.35 Present standards for evaluating the efficacy of ECT and antidepressant drugs differ. Antidepressant drugs are rated as effective when they reduce depression rating scale scores by 50%, but such treatment leaves many patients with debilitating symptoms. In evaluating the antidepressant response to ECT, however, we seek (and achieve) reductions in scores of 60% to 80% with single digit scores on depression rating scales as the outcome ratings. The recent shift from ‘symptom reduction’ to ‘cure’ in the aims of psychiatric treatment, encourages a wider use of ECT in treating delusional depression, schizophrenia and schizo-affective disorder, catatonia, and mania.

5.1. Delusional depression To optimize treatment with imipramine, Glassman and his associates monitored its use with weekly serum levels.36 Despite adequate imipramine serum levels, only three of 13 delusional depressed patients (30%) improved, while 14 of 21 non-delusional patients (66%) improved. Nine of the ten unimproved delusional patients recovered with subsequent ECT. They concluded that the treatment of delusional depressed patients with a tricyclic antidepressant alone prolonged their suffering, lengthened their period of risk for suicide, and unnecessarily exposed them to toxicity. This report was quickly verified.37 Italian investigators treated 437 depressed hospitalized patients with imipramine in doses of 200–350 mg / day for 25 days or longer.38 Of these, 247 patients (57%)

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The safe treatment of patients with recent myocardial infarction, cerebrovascular injury, or cerebral vascular malformation requires special attention to the control of blood pressure, heart rate, and oxygenation. The presence of a growth within the skull, once thought an absolute contraindication to the use of ECT, is no longer considered a bar. Patients with intracranial tumors or vascular malformations can be safely treated (Abrams, 1997; Greenberg et al., 1986, 1988; Patkar et al., 2000; Salaris et al., 2000). 34 Despite its clinical success, ECT was seen to contrast sharply with the rapidly expanding Freudian ethos in psychiatry. The many German and Austrian psychoanalysts who fled to UK and the US aggressively argued that they had the true understanding of psychological phenomena, their disorders, and their relief. They established schools of psychoanalysis, and as soon as World War II ended, began an overt campaign to disparage ECT as a nonpsychotherapeutic method (Fink, 1979, 1991, 1999; Lebensohn, 1984, 1999; Shorter, 1997).

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The sample sizes were small, and in retrospect, the conclusion of clinical equivalence of antidepressants and ECT is seen as a type II statistical error. The evidence for the superior efficacy of ECT over antidepressant drugs is seen in its efficacy when drugs have failed, in the speed of response, in the efficacy in the more severe forms of depression (as delusional depression, schizo-affective disorders), and in its tolerance by the elderly. Comparisons of insulin coma and chlorpromazine also found the treatments to be equivalent in efficacy, but chlorpromazine was less expensive, easier to administer, and less riskful. Insulin coma was quickly discarded (Fink et al., 1958). Lobotomy was replaced by psychoactive drugs, but without the benefit of direct comparisons. 36 Glassman et al. (1975), Kantor and Glassman (1977). 37 Kroessler (1985). 38 Avery and Lubrano (1979).

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recovered and were discharged. Each of the 190 unimproved patients was next treated with bilateral ECT, and of these, 156 (72%) recovered. Of the depressed patients who had not improved with imipramine, 43% were delusional as well as depressed. By 1985, we knew that only a third of patients with delusional depression would recover when treated with antidepressant drugs alone and half would recover when treated with antipsychotic drugs alone. However, two-thirds of those treated with ECT or with the combination of high doses of both antidepressant and antipsychotic drugs became well.39 In a 2-year study of late-life depression, 47% of the delusional depressed patients treated with medication relapsed earlier and more often than the nondelusional depressed (15%).40 The delusional form of depression proved particularly resistant to medication. The recognition of delusional depression is difficult, however, and treatment failure is frequently associated with sub-optimal dosing and inappropriate selection of medicines. At three leading academic hospitals, only 4% of delusional depressed patients had received adequate trials of medication treatment before being referred for ECT.41 The failure to recognize and adequately treat cases of delusional depression with medication (and with the early use of ECT) led one author to inquire why patients with delusional depression had to sustain inadequate medication trials before being referred for ECT.42 The difference in response of delusional depressed from non-delusional depressed patients led to a call for the separate classification and separate treatment algorithms of these disorders.43 Post-partum depressions often take on delusional qualities. These are difficult to treat with medications alone, but they respond rapidly to ECT.44

5.2. Pseudodementia Another highlight of the role of ECT in treating severe depression is the description of a severe dementia among depressed patients, a dementia that is hardly distinguishable from that of degenerative brain diseases. Labeled ‘pseudodementia’, it responds to ECT.45

5.3. Depression in the elderly Clinicians today favor SSRI antidepressants for their lesser toxicity when compared to the tricyclic drugs. But the depressions of the elderly are difficult to treat, in part because of persistence and recurrence, and the interactions with the many medicines used by the elderly to treat systemic disorders. The role of ECT has broadened in treating the elderly, and geriatric specialists are the largest segment of APA members seeking qualification in ECT.

5.4. Catatonia Mutism, negativism, posturing, rigidity, and other motor signs comprise the syndrome of catatonia. While DSM and ICD classification systems pigeonhole catatonia as a form of schizophrenia, its incidence is much higher in patients with affective illnesses (both mania and depression), and among those with neurotoxic and systemic illnesses. In depressed patients, the catatonic signs respond poorly to antidepressant treatments, but do respond to barbiturates and benzodiazepines. When these fail, ECT is effective.46

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Kiloh (1961), Bright-Long and Fink (1993), Fink (1999). Interest in catatonia as a feature of affective illness was sparked by the studies in the 1970s of Abrams and Taylor (1976). Since then, catatonia has been identified in 6–9% of acute admissions to academic psychiatric hospitals. The syndrome does not respond to antidepressant drugs but does to benzodiazepines, and when these fail, to ECT (Fink, 1997a, 1999; Petrides and Fink, 2000). A compelling benefit of this experience is seen in the clarification that patients with the neuroleptic malignant syndrome are suffering from malignant catatonia and not a dopamine abnormality requiring dopamine agonists (bromocriptine) and muscle relaxants (dantrolene) for relief. ECT is the effective treatment for NMS when benzodiazepines in high dosage fail. 46

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Kroessler (1985). Flint and Rifat (1998). 41 Mulsant et al. (1997). 42 Abrams (1998). 43 Schatzberg and Rothschild (1996), Rush et al. (1998), Crismon et al. (1999). 44 ECT is also effectively used in the psychoses that occur during pregnancy. Concerns about the teratogenetic effects of medications leads to the frequent use of ECT during the first two trimesters of pregnancy. 40

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5.5. Schizophrenia and schizo-affective disorders ECT was introduced and widely used as the treatment for schizophrenia in the decades before the discovery of antipsychotic drugs replaced such use. Recent re-assessment of the efficacy of ECT finds that ECT had been as effective, if not more so, than the antipsychotic drugs.47 ECT was particularly effective when used to augment medicines, and such combined treatment is increasing.48

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clozapine. The committees supporting its study argued that patients would have to fail two medication trials with neuroleptic drugs of two different classes, at adequate clinical dosages, each of a minimum of 6 weeks, before referral for clozapine. Failure to improve with this rigorous standard justified exposure to a potentially toxic alternative.52 Based on that model, ECT should be applied after two antidepressant medication trials have failed, or earlier in those who are suicidal, suffering from inanition, catatonia, or are systemically ill.53

5.6. Mania When ECT was introduced to treat manic-depressive insanity, both the depressive and the manic phases of the illness were effectively relieved, as were patients with manic excitement, delirium, and psychosis. With the introduction of lithium and the neuroleptic drugs, such use became infrequent. But the relative inefficacy of these agents when used singly has led to triple and quadruple medication therapies. The role of ECT is being reconsidered, especially in saving lives in patients in delirious mania and in rapid-cycling manic states.49

6. Search to understand the mechanism of action A frequent objection to the use of ECT is that practitioners do not understand its mechanism of action. Putting aside the reality that we hardly understand any of the interventions that we use for mental disorders, we do know much about the physiology of ECT. Many hypotheses have been proposed.54

6.1. Amnestic theory 5.7. ‘ Last resort’ The attitude to reserve ECT as ‘the last resort’ after many medication trials have failed is a questionable practice, doing a disservice to many who may have benefited.50 Treatment algorithms recommend repeated trials of antidepressant drugs, first alone, then in combinations, and then with augmenting strategies. ECT is considered after all else has failed. Such assignment as the last resort is wrong, both as a matter of humanity (to ease suffering as rapidly and as safely as possible) and of economics since the overall cost of a course of ECT is often less than repeated courses of medications.51 A more reasonable guideline for the use of ECT comes from the logic used to evaluate the toxic medicine

Amnesia, second to the profound effects of ECT on mood and thought, is prominent in ECT. When ECT was introduced into psychiatric practice, the Freudian belief that mental disorders rose from unconscious conflicts, and that relief came when the conflicts were brought to consciousness by the free association of thoughts and the analysis of dreams and humor dominated clinical ideology. ECT was seen as effective because it buried conflicts deep in the unconscious, making them inaccessible. Amnesia was the therapeutic agent. But as treatment skills increased (oxygenation, lower energies, less damaging current forms) the effects of seizures on memory became less overt, and the amnesia theory was less

47

52

48

53

Fink and Sackeim (1996). A well controlled study of ECT augmentation of clozapine in schizophrenic patients who have failed adequate trials of at least two antipsychotic medicines as well as clozapine is in progress at the Long Island Jewish Hillside Hospital. 49 Mukherjee et al. (1994), Fink (2000). 50 Fink (1997b, 1999). 51 Markowitz et al. (1987), Steffens et al. (1995).

Kane et al. (1988). It is difficult to understand how the ‘expert’ committees come to their algorithms for treating depression. The authors do not cite experimental evidence for their recommendations, arguing that their judgments are based on ‘clinical experience’. They ignore the experience that ECT is more effective than the antidepressant regimens that they espouse (Fink, 1997b, 1999). 54 Fink (1979, 1999, 2000).

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credible. It was also discarded because psychodynamic explanations were no longer accepted.

6.2. Autonomic nervous system theories In the balance between the activities of the sympathetic and parasympathetic nervous systems, ECT enhances the brain’s cholinergic activities. During the course of ECT the cerebrospinal fluid levels of acetylcholine and cholinesterases rise. Anticholinergic drugs reverse both the mood and physiologic effects of ECT and such findings led to a cholinergic explanation of ECT.55 Support for this view came from the association between ECT-induced persistent slowing of the EEG and clinical improvement. The theory is still viable, but like the other concepts based on brain neurohumors, no operative mechanism has been described.56

6.3. Neurohumoral theories Explanations of the benefits of antidepressant drugs are dominated by other brain neurohumors (epinephrine, norepinephrine, serotonin, and dopamine). Researchers opine that the effects of ECT also arise from their impact on the same neurohumors and receptors.57 But detailed studies, in both animals and man, fail to find consistent changes in neurohumors or their receptors in ECT and ECS, making these hypotheses untenable.58

6.5. Neuroendocrine theories Endocrine functions of the brain control all life processes — waking and sleeping, vigilance, feeding and digestion, procreation and sex, and maturation and aging. Surprisingly, the severe mentally ill have abnormal neuroendocrine functions and in tests of hormone integrity, as the dexamethasone suppression test and the thyroid response to thyrotropin releasing hormone, depressed patients are abnormal. These abnormalities resolve when the illnesses resolve, and recurrence of the illness is associated with abnormal tests.60 Abrams and Taylor 61 and later Fink and Ottosson 62 proposed that seizures changed the hormone balances of centrencephalic (brain stem) structures, and that such changes were the mechanism of recovery. The CSF is rich in peptides that arise mainly from the hypothalamus and the pituitary gland.63 A brain seizure first releases the remaining peptides stored in the glands and then stimulates the cells to produce more peptides. When peptide deficiencies are corrected, patients improve. Disorders in mood, thought, memory, and motor functions are associated with disorders in as yet unidentified peptides.64 Seizures release higher concentrations of brain peptides, relieving defects that may have been the basis of the clinical syndrome.65

60

6.4. Anticonvulsant theories Like memory effects that increase with numbers of seizures, the seizure threshold rises with successive treatments. The rise is considered a favorable prognostic sign and some psychologists propose that the rise in threshold is central to the antidepressant efficacy. Studies focused on changes in GABA, suggested as the operational neurohumor, fail to find consistent changes.59 55

Fink (1966). Fink and Kahn (1957), Fink et al. (1974). Recent EEG studies confirm the finding that behavioral improvement is associated with EEG slowing, especially frontal slowing of the EEG in the interseizure record (Abrams et al., 1973; Sackeim et al., 2000). 57 Mann (1998). 58 Fochtmann (1994, 2000). 59 Sackeim (1999). 56

Fink (1986a), Rush et al. (1996). Abrams and Taylor (1976). 62 Fink and Ottosson (1980), Fink (1979, 1990, 1999, 2000), Mathe´ (1999), Sattin (1999). 63 Bergland (1985). 64 The hypothesis assumes that different peptides regulate thought, mood, motor functions, and memory, thus allowing ECT to be so broadly effective. Other interventions are limited to narrower aspects of their functions, being limited as antidepressant, antipsychotic, or antimanic agents. 65 In CSF studies using chromatography, Bergland (1985) reported that seizures to both increase the number and concentration of many substances, but also to decrease the concentration of some substances. When the neuroendocrine theory was first proposed, it was challenged for its interpretation that seizures elicit brain peptides that replace deficiencies, in a fashion similar to the action of exogenous insulin or thyroid substances to replace their deficiencies. Neuroendocrinologists argued that such an assumption was premature, that seizures might release substances that inhibited brain functions. The anticonvulsant theory, focused on GABA as an inhibitor of neurotransmission, is an example of this view. 61

M. Fink / Journal of Affective Disorders 63 (2001) 1 – 15

We can understand why seizures using unilateral placement of electrodes are less effective, even at very high dosages, than treatments with bilateral electrodes. The latter force electric currents to pass directly through centrencephalic brain stem structures. It suggests why electric and magnetic currents to the brain, or other procedures that affect the brain hemispheres and not the basal structures, are ineffective in relieving mental disorders unless seizures are induced.66 The release of stored peptides explains the immediate relief seen in some patients, but it is the stimulation of new production that sustains the benefits when continuation ECT is used. This theory has been criticized for not identifying the specific peptides that may be involved in such actions, and the lack of evidence of direct connections between brain peptides and behavioral responses. The indirect evidence provided by the present neuroendocrine tests is considered unsatisfactory.67

7. Search for public and professional acceptance When convulsive therapy was hailed as an effective treatment of the severe mentally ill, the alternative treatment options were insulin coma, psychosurgery, psychoanalysis, and psychotherapy. In the flood of emigration from Nazism and Communism in the 1930s, many physicians acquainted with Freudian dogma came to the US and the British Commonwealth. They found fertile ground for the theories that opening unconscious memories to awareness resolved the neuroses and psychoses. Other emigres brought the biological treatments in their baggage. Immediately after the war, a cabal of psychoanalysts, headed by the William and Karl Menninger, led psychiatry to psychoanalysis. They formed an elitist organization, the Group for the Advancement of Psychiatry, and immediately issued a broadside against ECT as their first pronouncement.68 Psychoanalysts quickly took over the leadership of the American Psychiatric Association, established

psychoanalytic schools, and soon psychoanalysts were at the helm of the departments of psychiatry at US medical schools and hospitals. Physicians interested in advancing their academic careers and in treating the worried-well in office settings flocked to analytic schools.69 To treat one’s patients with ECT was seen as incompetence in the ‘higher’ forms of psychiatric practice. As the psychotherapies achieved public acceptance, psychologists, nurse practitioners, social workers, and the clergy came to join the minions of psychoanalysts and psychotherapists. They separated their offerings from the prescriptions of medicines and the use of ECT by physicians. Their membership organizations took public positions to restrict the availability of ECT. The introduction of psychotropic medicines quickly replaced the somatic therapies but took longer to replace the psychotherapies. When the drugs faltered in getting patients better, ECT was recalled to practice in the 1970s. It was an inopportune time for its resurrection. The nation was reeling under protests against government conscription of soldiers for an unheralded war in Vietnam. Protests spread to the forceful hospitalization of the mentally ill, and to their treatments with electroshock and lobotomy. Psychiatrists were portrayed as agents of the state by popular leaders as Thomas Szasz and Erving Goffman in the US, Michel Foucault in France, and Ronald Laing in Great Britain.70 The films Snakepit and One Flew Over the Cuckoo’ s Nest portrayed the worst aspects of hospital care. The newly hatched Church of Scientology found a ready target in psychiatry, exaggerating the worst aspects of electroshock, forced hospitalization, and treatments of children. They spawned lay groups, many led by former patients, who attacked psychiatry in legislatures, demanding that ECT and lobotomy be outlawed. Such demands led the California legislature in 1974 to severely restrict the use of ECT. Such attacks have been successful in at least five states in limiting the availability of ECT, the latest being restrictions in Texas in 1993.71 The state legislative 69

66

Post et al. (1999). Cooper et al. (1990), Nutt (1990), Post (1990), Sackeim and Devenand (1990). 68 Fink (1979, 1991, 1999). 67

11

The GI Bill encouraged veterans returning from World War II to undertake additional schooling by paying the tuition fees and monthly subsistence stipends. Many physicians used these funds to enroll in psychoanalytic schools. 70 Szasz (1961), Shorter (1997). 71 Fink (1991, 1999).

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restrictions are accompanied by the lack of facilities for ECT at most state (VA, municipal) supported mental hospitals. The unavailability of the treatments means that the professional staff is deterred by the administrative hurdles that make it almost impossible to transfer a patient to a facility equipped to give the treatment. More important, their inexperience with ECT limits the physicians’ abilities to prescribe it. A 10-year review of the experience in a Pennsylvania state facility that referred patients to a university center for ECT found that less than 0.4% of admissions had received the treatment (This is in contrast to the 6–12% of admissions to academic mental hospitals who receive ECT).72 Federal government-supported research for more than two decades has been focused on claims that ECT damages the brain and leads to permanent memory loss, and not in clinical issues or studies of its mechanism of action. Most studies sought to minimize the impact of ECT on memory functions and to sustain therapeutic efficacy. Manufacturers had already fashioned brief-pulse energy devices and many studies had shown that unilateral electrode placement was less effective than bilateral placement. Nevertheless, for more than 20 years, studies of the relationship between electrode placement and energy made up almost the whole portfolio of ECT research funded by the National Institute of Mental Health.

8. ECT in the 21st Century The efficacy and safety of ECT for depressive mood disorders encourages greater attention to its use and to the training of its practitioners. Evidencebased medicine is increasingly encouraged as the standard for clinical practice. In comparisons of ECT 72

Sylvester et al. (2000). Twenty-one patients received ECT in a 10-year period. Seventeen records could be retrieved. The lengths of stay for most had been less than a year before referral for ECT. The mean number of ECT was 12.2. There were no medical complications. 65% (11 / 17) were discharged immediately after the ECT course. Of seven patients who had multiple restraint or seclusion episodes, six had no further episodes after ECT. The seventh experienced a dramatic decrease in number and total hours of episodes. With such benefits, it is shameful that so many public hospitals do not provide ECT for their patients.

and alternative medications, the efficacy of ECT compels its earlier consideration and its broader use. Unfortunately, ‘official’ treatment algorithms by committees of experts place ECT at the bottom of a list of options, encouraging prolonged courses of one medicine after another without testing their utility. ECT is not just another ‘me, too’ medicine. It is a unique intervention with a broad and profound impact on brain function and behavior, surely warranting more attention to its neuroscience. A greater understanding of the effects of seizures on brain mechanisms is, I believe, the source of ways to replace both ECT and the present spate of ‘me, too’ psychotropic drugs with a more acceptable and more effective treatment of severe mental illnesses.

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Sylvester, A.P., Mulsant, B.H., Chengappa, K.N.R. et al., 2000. Use of electroconvulsive therapy in a state hospital: A 10-year review. J. Clin. Psychiatry 61, 534–539. Szasz, T.S. (Ed.), 1961. The Myth of Mental Illness. Foundations of a Theory of Personal Conduct. Paul B. Hoeber, New York, p. 337. Ulett, G., Smith, K., Gleser, G.C., 1956. Evaluation of convulsive and subconvulsive shock therapies utilizing a control group. Am. J. Psychiatry 112, 795–802.