Among ECT’s negative effects on cognitive functions, the immediate-, medium- (“subacute”) and long-term effects must be distinguished. Immediately after an ECT treatment session, the patient is in a state comparable to that following an epileptic seizure – characterized by confusion and neurological abnor-malities. Depending on the technique used, these immediate effects may last from a few minutes to a few hours. In this respect, bilateral electrode place-ment, the use of sine waves, high electrical charges, and the administration of ECT treatment sessions in close sequence cause longer-lasting immediate effects [American Psychiatric Association and Task Force on Electroconvulsive Therapy, 2001, p. 68;
Sackeim et al., 2000b; Sackeim, 1992, p. 186].
Medium- and long-term effects include memory effects (verbal and non-verbal), as well as effects on other cognitive functions. Among the memory effects, the negative effects on pre-ECT
9. E-mail communications with Dr. Yesekiel Ben-Ari, Institut de Neurobiologie de la Méditerranée, INSERM, Marseille, France, March 18, 2002; Dr. Thomas Sutula, University of Wisconsin, (Madison, USA) March 21, 2002; and Dr. Graeme Jackson, Brain Research Institute, (Melbourne, Australia), March 27, 2002.
10. Dr. Graeme Jackson, Director of the Brain Research Institute in Melbourne, Australia, reported the history of an elderly patient who presented significant post-ECT-amnesia problems, which clinicians attributed to dementia problems. However, a magnetic-resonance investigation demonstrated a sclerosis of the hippocampus, which was absent on a previous magnetic-magnetic-resonance image taken 2 years before (e-mail communication, March 27, 2002).
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memory, also called retrograde amnesia, and the negative effects on the memorization of new events after the ECT treatment session or after the end of treatment, also known as anterograde amnesia, must be distinguished. Anterograde amnesia, as measured by various neuropsychological tests, disappears in the months following the end of ECT treatment [Calev et al., 1991; Sackeim et al., 2000b; Sackeim, 1992].
However, retrograde amnesia does not generally disappear as quickly. Patients whose state of confu-sion lasts longer are more at risk of presenting signif-icant, or even permanent, retrograde amnesia [Sobin et al., 1995]. Retrograde amnesia primarily affects the memory of the closest events in a course of treat-ments, but it may extend to events that occurred several years previously [Sackeim, 2000].
The possibility of permanent retrograde amnesia has been the subject of bitter exchanges between ECT proponents and opponents. ECT oppo-nents affirmed the existence of permanent memory disturbances and interpreted this fact as a sign of brain injury. According to certain theories, the thera-peutic effect was even attributable to effects on cogni-tive functions. However, the results of much research indicates that the negative effects on cognition are independent of efficacy [Calev et al., 1991; Sackeim et al., 2000b; Sackeim, 1992].
An editorial published in The Journal of ECT in the year 2000 entitled “Memory and ECT:
From Polarization to Reconciliation,” summarized the closing gap between the various positions concerning the permanent effects on the anterior memory [Sackeim, 2000]. Although the existence of such effects is now generally accepted, its probability is unknown. In his editorial, Sackeim interestingly quoted a paragraph on this subject taken from the impending practice guidelines of the American Psychiatric Association:
“In many patients the recovery from retrograde amnesia will be incomplete, and there is evidence that ECT can result in persistent or permanent memory loss.” [Sackeim, 2000, p. 89]
In the final version of these practice guide-lines, the sentence was slightly modified, as follows:
“In some patients the recovery from retrograde amnesia will be incomplete, and there is evidence that ECT can result in persistent or permanent memory loss.” [American Psychiatric Association and Task Force on Electroconvulsive Therapy, 2001, p. 71]
The replacement of the word “many” by
“some,” which makes reference to the frequency of the permanent effects on the anterior memory very clearly indicates that the probability of such effects is not known with certainty.
The ability to detect an effect depends on the number of persons included in the study. In this regard, Phase III drug studies generally comprise 2,000 to 3,000 patients [Asscher, 1989, p. 213].
Here, the number of patients studied is sufficient to detect side effects between one per 100 and one per 1,000 [Hanley and Lippman-Hand, 1983; Lewis, 1981]. The detection of rarer side effects, such as aplastic anaemias due to certain medications such as chloramphenicol, requires several tens of thousands of patients [Schafer, 1997].
Research on ECT’s effects on the memory has been conducted with a few dozen patients only.
Among all the studies of a high methodological quality we have located, the largest study included only 51 patients treated by ECT. A meta-analysis of the various studies proved impossible because of the heterogene-ity of the measurement instruments, certain of which were not psychometrically validated. In addition, statis-tical analysis of the results was frequently conducted inappropriately [UK ECT Review Group, 2002, p. 58].
The vast majority of these studies examined damage to the verbal memory, to which the left hemi-sphere of the brain contributes. In this respect, right unilateral electrode placement greatly decreases these effects and is as effective when used with elec-trical charges several times greater than the seizure threshold [McCall et al., 2000; Sackeim et al., 2000a]. Few studies have examined the unilateral right application of ECT on the visuospatial memory, which depends almost exclusively on the right hemi-sphere of the brain. Each of two 15-patient studies demonstrated some damage to the visiospatial memory, which disappeared entirely within a few days [Hasse-Sander et al., 1998] or a few weeks [McCabe, 1995] after the last ECT treatment session.
Taking into account the low patient numbers in these two studies, the possibility of permanent effects on this form of memory should be a top priority of future research.
The study of ECT’s side effects is complicated by damage to the cognitive functions by the depres-sion itself. Concerning the effects of ECT treatment on cognitive functions other than those of memory, a systematic review of the various studies published between 1975 and 1993 concluded that
“with early methods of ECT administration (sine wave, high dose), these effects are larger than those of depression. They are less pronounced, and usually do not exceed the effects of depres-sion, when modern methods of ECT administra-tion (brief pulse, moderate or low dose) are used. […] The results of this review argue that clinicians should take the non-memory cognitive effects of ECT into account, and patients should be informed of their existence before they sign consent for ECT.” [Calev et al., 1995, p. 505]
Certain ECT practitioners continue ECT after the end of the initial treatment, with less frequent treatment sessions (between one and two per month).
This form of treatment is known as maintenance ECT.
The effects of this treatment mode on the cognitive functions have seldom been studied [Rabheru and Persad, 1997]. In a case description, a patient presented a state of dementia after two years of maintenance therapy, but her condition gradually improved over a nine-month period after the treat-ment was stopped [Regestein et al., 1975].
The anaesthesia itself may affect the cogni-tive functions in the short, medium and long term. In elderly patients particularly, anaesthesia may cause cognitive dysfunctions, affecting visual and auditory attention as well as various forms of memory.
Together, these cognitive disabilities are called “post-operative cognitive dysfunction,” or POCD. Although the aetiology of this dysfunction is not yet known, it may be linked to the neurotransmitters in the cholin-ergic system [Ancelin et al., 2000]. A study on the incidence of POCD in a population of individuals 60 years of age or older who underwent major non-cardiac surgical interventions established the inci-dence of POCD at 9.9% after three months and at approximately 1% one to two years after the inter-vention [Abildstrom et al., 2000]. We do not know the incidence of POCD in younger patients or in those who have undergone minor surgery [Rasmussen, 1999].
In the absence of accurate knowledge on the impacts of short-term anaesthesia such as that used for an ECT treatment, we cannot distinguish the impacts of the anaesthesia from those of the electri-cal stimulation itself. In a randomized, double-blind study of 53 patients treated by ECT, no difference was noted between the two most commonly used anaesthetics in ECT, namely propofol and metho-hexital, concerning their effects on anterograde amnesia [Martensson et al., 1994]. However, a high dosage of methohexital may increase
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associated effects on memory [Miller et al., 1985].
The effects of the anaesthetics on the cognitive func-tions must be minimized through the use of appro-priate levels of these medications. In practice, the doses used often seem excessive in relation to prac-tice-guideline recommendations. For example, in a prospective study of 52 patients who had received ECT in Edinburgh, 92% received methohexital doses that were higher than the recommendations of the American Psychiatric Association, and 98%
received doses that were higher than the more strin-gent recommendations of the Royal College of Psychiatrists of the United Kingdom and Ireland [Cook et al., 2000].
The impacts of damage to the cognitive func-tions may be complex. In a study evaluating the risks of ECT in a patient population 80 years of age and older, it was noted that 36% had suffered falls during their hospitalization [Cattan et al., 1990]. In a retro-spective study of 1,834 patients admitted to a psychogeriatric unit, ECT was associated with at least one fall during the hospitalization, with an adjusted odds ratio of 3.16 (p < 0.001, 95% confidence inter-val of 95% 2.10 to 4.75) [de Carle and Kohn, 2001].
According to the authors, these falls could be due to cognitive problems caused by ECT.
Several conclusions may be drawn from the various studies that have examined the negative effects of ECT on the cognitive functions:
• ECT has adverse effects on cognition, which generally do not last longer than a few weeks or months after the last treatment session. Right unilateral ECT has fewer negative effects than bilateral ECT, even though the former involves higher electrical charges than the latter.
• Compared to studies on drugs, studies on the side effects of ECT have been conducted
on very small number of patients, and the determination of the risk levels of the various effects is therefore uncertain. This particu-larly concerns the effect of right unilateral ECT on the cognitive functions of the right hemisphere.
• A number of patients suffer permanent effects to the anterior memory (retrograde amnesia); however, it is impossible to quan-tify the risk level of these effects. A good stimulation technique and an appropriate dosage of anaesthetic may significantly reduce the risk of adverse effects on the cognitive functions. Such risks may be decreased by the development of quality control programs to ensure compliance with the practice guidelines.
• Research efforts must be devoted to the adverse effects of ECT on the cognitive func-tions, particularly on the level of risk of permanent retrograde amnesia, on the impact of right unilateral ECT, on the impact on cognitive functions other than memory, and on the impact of these effects on the quality of life of patients.
The risks of reversible and irreversible adverse effects of ECT on the cerebral functions must be taken into consideration by the physician and the patient when they must jointly decide whether or not to use this therapy. Moreover, in connection with ECT use, monitoring strategies focused particularly on the risk of permanent retrograde amnesia could be developed. These strategies could be based on those developed to monitor the adverse effects of drugs after they reach the market. The development of neuropsychological-measurement tools suitable for clinical practice constitutes the first challenge of such a strategy [Kellner, 1996]. In the immediate term,
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rigorous application of practice-guideline recommen-dations regarding the stimulation technique and anaesthetic dosage constitutes the best means of minimizing the adverse effects of ECT on the cognitive functions.
22
“The vast majority of psychiatrists agree that electroconvulsive therapy is highly effective in depression, manias, catatonias, and in affec-tively laden schizophrenic conditions. The weight of clinical and scientific evidence is overwhelming.” [Greenblatt, 1984]
“The clinical literature establishing the efficacy of ECT in specific disorders is among the most substantial for any medical treatment.”
[American Psychiatric Association and Task Force on Electroconvulsive Therapy, 2001, p. 5]
Seventeen years separate these two quota-tions, but their messages are similar: ECT is an effec-tive therapy for several mental illnesses. In this section, we will define the analysis framework through which the efficacy of this technology will be assessed.
The efficacy of a technology or an interven-tion is its capacity to produce an expected benefit for a specific health problem, in conditions defined for individuals in a specific population. It is therefore necessary to specify the benefit expected from the administration of ECT, the capacity of ECT to produce this benefit, the health problem concerned, the type of individuals targeted, and the conditions of use of this form of treatment.
We will first present the methods used to eval-uate the scientific evidence concerning the interven-tion’s capacity to produce a benefit. In the next section, we will use the example of depression to define vari-ous types of benefits that may be used in studies of therapeutic efficacy for the same illness. We will then examine the uncertainties concerning the classification of mental illnesses and their consequences on treat-ment-efficacy measurements. These conceptual sections are followed by a summary of current knowl-edge on the efficacy of ECT for certain illnesses. The conditions of use of ECT will be dealt with in the prac-tice section, in which particular emphasis will be placed on ECT regulation mechanisms.