bruce.charlton@newcastle.ac.uk

Abstract -- It is proposed that ECT is not specifically mood-elevating or anti-depressant but that its effect is as an anti-delirium intervention. I suggest that ECT exerts its primary therapeutic effects by inducing a generalized epileptic seizure which operates on the brain like a deep and restorative sleep which acts rapidly to resolve delirium. Provided that the diagnosis is made using sufficiently sensitive criteria, delirium is here assumed to be a common feature of many so-called ‘functional’ psychoses - frequently occurring as a consequence of sleep deprivation, and leading to symptoms such as hallucinations, bizarre delusions and psychomotor retardation. Testable predictions of this ‘anti-delirium’ theory of ECT action are described.

Introduction

It is generally agreed that the therapeutic effect of ECT comes from the grand mal convulsion (rather than from the anaesthetic, the passage of electricity through the skull and brain, or other aspects of the maneuver). Hence any means of inducing a generalized epileptic seizure (eg. inhalation of camphor or injection of leptazol) is considered to be equally effective [3,5]. This suggests that ECT action involves large volumes of brain tissue, since it is highly implausible that a fit would have a highly focused effect on a specific brain region. It also suggests that the therapeutic action of ECT is ‘simple’, in the sense of working by its effect on basic biological variables such as arousal. Furthermore, any explanation of the effectiveness of ECT should account for the broad spectrum of diagnostic categories in which it is effective. As described above, the potential indications go beyond the most common usage of ECT in severe major depression with biological features.

My suggestion is that the primary therapeutic physiological effect of ECT is in the treatment of delirium; probably by means of simulating or inducing physiologically ‘natural’ and restorative sleep. A course of ECT cumulatively leads to electroencephalogram (EEG) changes characterized by increased amplitude and reduced frequency (‘delta’ activity) somewhat similar to that seen in normal sleep [6]. It is likely that such EEG changes are correlated with improved clinical response rates and reduced likelihood of relapse [3].

Delirium in the ‘functional’ psychoses

Delirium presents with a non-specific prodromal phase of increasing perplexity, fearfulness and distractibility [7,8]. However, the clinical diagnosis of delirium has traditionally been confined to a much more severe stage of psychopathology in which disorientation, grossly altered or ‘clouded’ conscious level (somnolence or agitation), and a wide range of psychotic symptoms such as hallucinations and delusions have supervened (e.g. DSM-IV or ICD-10 criteria). I suggest that this is a crude conceptualization of delirium, and that early stages of impaired brain function are in fact common in the so-called ‘functional’ psychoses (schizophrenia, mania and depression). Biological and psychotic features of depression (and EEG changes) are usually predictive of a good response to ECT [3,9]. It is proposed that such symptoms and signs are correlated with the presence of delirium - some as causes, and others as consequences (see below) - and that this explains their prognostic value in ECT.

There has traditionally been a requirement, dating from Kraeplin, that the functional psychoses can only be diagnosed in the absence of clouded consciousness or disorientation. The assumption is that ‘clear’ consciousness and retained-orientation rules out significant ‘organic’ pathology. However, this is to adopt a narrow and insensitive definition of delirium; and to the contrary I would argue that delirium is indeed an essential component of the clinical picture in ‘psychotic’ depression, mania and schizophrenia where hallucinations and bizarre delusions occur. This assertion - although controversial - would readily be testable using a definition of delirium based upon subtle (‘prodromal’) symptoms such as perplexed affect and distractibility, backed up by the ‘gold standard’ of serial EEG monitoring.

Action of ECT

It is suggested that ECT is a specifically effective treatment only in those depressed patients who are at an advanced stage of their illness, and in whom delirium (and the putative delirium-related symptoms such as psychomotor retardation, hallucinations and delusions) is a feature. Stressors such as insomnia and acute weight loss might further be expected to lead to changes in physiological and metabolic status which amount to a systemic illness with immune activation [11]. It has been powerfully argued that depression may be a consequence of a cytokine-mediated psycho-motor malaise including the typical pattern of ‘sickness behavior (including demotivation, inertia, anhedonia, exhaustion, anorexia and sleep disturbance [12]) - sleep deprivation might be expected to synergize with any pre-existing systemic illness in the production of delirium.

Electro-convulsive therapy breaks this vicious circle by inducing a generalized epileptic seizure which acts upon the brain like a deep and restorative sleep - the distinctive features of which require further investigation. Subjectively satisfying and objectively physiologically-normal sleep is not always easily attained by pharmacological means, and ‘hangover’ effects from sedatives may cause troublesome daytime somnolence which further disrupts circadian rhythms - yet the benefits of sleep may be rapid and profound (e.g. [10]). In mania and delirium even a single ECT treatment may serve to disperse an excited, insomniac, hyper-active state [1,3,7]. When ECT is effective in depression, the patient often wakes from the first treatment feeling symptomatically improved and further improvement may follow sound sleep during the following nights.

Predictions

Secondly, properly-administered ECT, with a confirmed grand mal seizure, should be rapidly effective if it is going to be specifically effective. Cases which apparently improve only after many treatments over long periods of time would be expected to be responding to placebo effects, coincident therapeutic treatments (e.g. ongoing pharmacological or psychological therapies), or undergoing a natural remission.

Thirdly, improvement in ‘delirious symptoms’ such as psychomotor retardation, hallucinations and bizarre delusions may be immediate; but full resolution of the affective component of the illness would typically take longer. This staged improvement may be missed by the employment of ‘global’ depression scales (such as those by Hamilton or Beck). The delay in affective response to ECT may be explained on the general model that mood is a secondary consequence of cognitive functioning, and recovery of mood builds-up following an accumulation of positive cognitions. Sleep patterns and appetite are restored, and gradually the accumulated exhaustion of several months is repaired. Just as full recovery from influenza takes a few weeks, so the process of recovery from depression (which probably shares many common phenomenological, and probably pathological, features with influenza [11,12]) would be expected to proceed over a similar timescale [13].

To conclude - it is proposed that ECT is not primarily an antidepressant treatment. Instead ECT exerts its therapeutic effects on mood indirectly by simulating or inducing deep sleep to resolve delirium. If a less invasive substitute for ECT were desired, the priority would be to devise an equally powerful and rapid means of inducing physiologically restorative sleep.

Acknowledgement - comments and criticisms from David Healy were vital to the argument of this paper.

References

1. Small JG, Klapper MH, Kellams JJ, Miller MJ, Milstein V, Sharpley PH, Small IF. ECT compared with lithium in the management of manic states. Archives of General Psychiatry 1988; 45: 727-732.

2. Fink M, Sackeim S. Convulsive therapy in schizophrenia? Schizophrenia Bulletin 1996; 22: 27-39.

3. Abrams R. Electroconvulsive therapy 3rd edition. New York: Oxford University Press, 1997.

4. Stromgren LS. ECT in acute delirium and related clinical states. Convulsive therapy 1997; 13:10-17.

5. Slater E, Roth M. Clinical Psychiatry 3rd edition. London: Balliere Tindall, 1977.

6. Niedermeyer E, da Silva L. Electroencephalography: basic principles, clinical applications , and related fields. Baltimore: Williams and Williams, 1993.

7. Lipowski ZJ. Delirium: acute confusional states. New York: Oxford university Press, 1990.

8. Charlton BG. Psychiatric implications of surgery and critical care. Chapter in Applied physiology for surgery and critical care. Ed M A Glasby & CL-H Huang. London: Butterworth Heinemann, 1995. pp 739-742.

9. Carney MWP, Roth M, Garside RF. The diagnosis of depressive symptoms and the prediction of ECT response. British Journal of Psychiatry 1965; 111: 659-674.

10. Wehr TA. Effects of wakefulness and sleep on depression and mania. In Sleep and biological rhythms: basic mechanisms and applications. Edited by Montplaisir J, Godbout R. New York: Oxford University Press, 1990. pp 42-86.

11. Hickie I, Lloyd A. Are cytokines associated with neuropsychiatric syndromes in humans? International Journal of Immunopharmacology 1995; 17: 677-683.

12. Hart BL. Biological basis of the behavior of sick animals. Neuroscience and Biobehavioral Reviews 1988; 12: 123-137.

13. Healy D. The suspended revolution. London: Faber, 1990.