Experimental studies of the mode of action of electroconvulsive therapy

Experimental studies of the mode of action of electroconvulsive therapy


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Acta psychiat, scand., Suppl. 145, 1960. ~ Copenhagen, Ejnar Munksgaard, 141 pp. In an area of study marked by inadequate design and incomplete controls, this monograph of well controlled clearly defined experimental investigations is a most welcome addition. These studies assess the significance of the duration and threshold of the induced seizures and the electroencephalographic responses in the convulsive therapy process in psychiatric patients by emphasis on the blocking of seizure activity by premedication with lidocaine (Xylocaine). Lidocaine, a synthetic local anesthetic agent, has been described as an effective anticonvulsant in experimental seizures with clinical properties similar to procaine (BEgNHAm~ and BoI-Im, Experientia, 1954, 10: 474). While the focus of the study is on the clinical problem of the therapy of endogenous depressions and the significance of memory impairment, the well defined methodology and clear descriptions of the experiments provides considerable neurophysiologic data. The neurophysiologic studies assess the changes in threshold and duration of electrically induced seizures, following lidocaine administration in patients, and a comparison of the effects oflidocaine, procaine, phenytoin and phenobarbital on seizures in curarized cats or encephale isole. Convulsive and post-convulsive EEG patterns, and the differential effects of modified and unmodified seizures on evaluations of improvement and on memory function in psychiatric subjects are described in the clinical studies. The authors report that lidocaine significantly decreases the duration of seizures, both clinically and electrographicaliy. In the EEG there is a decrease in the amount of spike activity with "better modulation" of seizure activity. Clinically, the tonic phase is abolished and the total seizure time decreased. Dose response curves are described, indicating maximum anticonvulsant effects for 3 to 4 mg/kg, with decreasing effects at higher dosage levels. The anticonvulsant effect of lidocaine was found additive to that of hexabarbital. In the cat preparations, an increase in stimulus intensity failed to compensate for changes in seizures induced by lidocaine or procaine but did compensate for changes following phenytoin and phenobarbital. In the clinical studies, the EEG was recorded during the seizure and for 25 min post seizure. Three types of seizure induction were s t u d i e d - - s u p r a t h r e s h o l d electrical (,4), threshold electrical (B), and threshold electrical modified by 4 mg/kg of lidocaine (C). Seizure duration and EEG patterns for A and B seizures were equivalent, while spike activity was reduced, and the duration of seizure and induced delta activity were shorter in C. In patients with endogenous depressions, clinical evaluations were undertaken after four treatments and after a complete series. After four treatments lidocaino

treated patients (C) showed less change in scores of anxiety, retardation or global behavioral change than patients treated with unmodified seizures (,4, B). There were no differences amongst the groups after the complete series. Significantly more treatments were needed for Group C than A or B. In tests of memory function applied prior to treatment and after five hours of selected treatments, impairment was related to treatment type, so that impairment was greatest in A, less in B and least in C and in untreated control subjects. These observations support the many reports that clinical change in convulsive therapy may be related to the duration of the induced seizure and the electrographic changes; and that both phenomena are directly dependent upon the intensity of the electrical stimulation and on the biochemical state of the nervous system at the time of the seizure. It is also consistant with earlier suggestions that the behavioral changes are related to the generalized seizure response and not to the electrical stimulation of the nervous system. As applied neurophysiologic studies, these reports are commendable. The authors' use of controls, specification of their population and of experimental variables, and the clarity of their reports and statistics provide an excellent research model. In the definition of electrical stimulation, however, the authors fail to define their terms "considerably above" and "moderately above" threshold. In EEG recording, no information as to area variability or interseizure EEG is presented, and seizure EEG patterns are described in general, non-quantitative terms. Despite its commendable methodologic features, one is left with the unsatisfied feeling of a promise, set forth in the title, that is unfulfilled. The mode of action of convulsive therapy cannot be explained by univariate analysis of electrical or seizure parameters. The choice of this variable alone provides the limiting factor in these studies. The absence of discussion of other significant aspects of the process - - as the personality, psychologic, sociologic, linguistic, or biochemical,--highlights the inadequacy of an assessment of as complex a process as the alteration of h u m a n behavior by analyses of simple variables alone. This report, with its many commendable methodological features, again indicates the need for the application of techniques of multivariate analyses in behavioral research. Yet, it does highlight the potential significance of studies of convulsive therapy in neurophysiology. Induced convulsions permits exquisite control of many experimental variables - - both neurophysiologic and behavioral - - and further studies are warranted. The volume is recommended highly to those interested in clinical neurophysiology and experimental psychiatry. MAx PINK