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 Table of Contents  
REVIEW ARTICLE
Year : 2018  |  Volume : 31  |  Issue : 3  |  Page : 735-741

Comparative study between cognitive adverse effects of bitemporal and bifrontal electroconvulsive therapy


1 Department of Neuropscychiatry, Faculty of Medicine, Menoufia University, Menoufia, Egypt
2 Department of Neuropsychiatric, Abbasia Mental Hospital, Cairo, Egypt

Date of Submission02-Nov-2016
Date of Acceptance02-Dec-2016
Date of Web Publication31-Dec-2018

Correspondence Address:
Mustafa A.E Mohamed
12 Belous-Elhawa Street, Elsanta, Gharbia Governorate
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/1110-2098.248756

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  Abstract 


In the past 26 years, an increasing number of articles have been published about the effects of bitemporal and bifrontal electroconvulsive therapy (ECT) on cognitive functions. Here, we review these studies, because there have been conflicting reports about the extent and persistence of ECT cognitive adverse effects related to the electrode position. In total, eight psychological and medical databases (Medline, PubMed, Psych INFO, Science Direct, EMBASE, CINAHL, Cochrane, and Web of Knowledge) were searched during June 2016 to investigated studies from 1991 to 2016. The initial search presented 35 articles, of which 13 met the inclusion criteria. The articles studied the cognitive adverse effects of bitemporal and bifrontal ECT. If the studies did not fulfill the inclusion criteria, they were excluded. Study quality assessment included whether ethical approval was gained, eligibility criteria specified, appropriate controls, adequate information, and defined assessment measures. Comparisons were made by structured review with the results tabulated. In total, 13 potentially relevant publications were included, most of the included studies found that cognitive impairment is less noticed in bifrontal ECT than bitemporal ECT. Few authors did not see evidences of the advantage of bifrontal ECT regarding cognitive profile. Evidence suggests that cognitive impairment does occur because of bifrontal and bitemporal ECT. Objective measures found cognitive impairment to be relatively fewer and lasting for a short term in bifrontal ECT than bitemporal ECT.

Keywords: bifrontal, bitemporal, cognitive impairment, electroconvulsive therapy


How to cite this article:
Elhamrawy LG, Shalaby AS, Saleh EG, Mohamed MA. Comparative study between cognitive adverse effects of bitemporal and bifrontal electroconvulsive therapy. Menoufia Med J 2018;31:735-41

How to cite this URL:
Elhamrawy LG, Shalaby AS, Saleh EG, Mohamed MA. Comparative study between cognitive adverse effects of bitemporal and bifrontal electroconvulsive therapy. Menoufia Med J [serial online] 2018 [cited 2019 Mar 25];31:735-41. Available from: http://www.mmj.eg.net/text.asp?2018/31/3/735/248756




  Introduction Top


Since its introduction in 1938, electroconvulsive therapy (ECT) has been administered as a safe and effective treatment for mental disorders, but public and professional concerns limit its use. ECT is a safe procedure with very low mortality rate calculated at 0.2 per 100 000 treatments, approximating the risk of general anesthesia. When used properly, under the appropriate guidelines and by a well-trained psychiatrist, ECT is extremely effective and safe[1].

The usual electrode placement include bitemporal (BT), right unilateral (RU), bifrontal (BF), and left anterior right posterior, and unilateral electrode placement. In most studies, RU ECT has been shown to cause fewer cognitive adverse effects but less antidepressant efficacy compared with bi (fronto) temporal ECT at certain intensities. At low dosage, RU ECT has weak effects, with long courses needed and low remission rate but negligible adverse effects. For reliable efficacy, clinicians must use a high stimulus dose, but then unilateral differs little from BT ECT in efficacy or adverse effects. The advantages of unilateral ECT should largely be in middle-sized doses, but there still is no clear method to match the dose to the individual patient. This uncertainty decreases the desirability of unilateral placement[2].

ECT cognitive and behavioral adverse effects probably correspond to temporary interference with brain function. Functional brain structures in the path of the electrical stimulus should be exposed to the most intense seizure activity. Interruption of the particular duties of these structures should correspond to the adverse effects specific to each type of electrode placement. Accordingly, an electrode placed over one anterior temporal lobe should disrupt memory, whereas electrodes placed symmetrically over both hemispheres (as with BT ECT) should produce greater disruption than asymmetrical stimulation[3].

The adverse effects of any particular electrode placement are primarily associated with the specific location of the electrodes, and these adverse effects accumulate along the course of treatment. It stands to reason that adverse effect aggregation should be diminished by decreasing the repetition of any particular placement. Changing electrode placement in reaction to nonresponse or adverse effects is a different issue, analogous to switching antidepressant medications[4].

Cognitive adverse effects from ECT can be separated into four different types: acute-onset delirium, gradual cumulative disorientation, anterograde amnesia, and retrograde memory loss. Although memory is altered in the period immediately following ECT, permanent memory loss is uncommon, even after numerous ECT sessions[5].

Acute-onset delirium from ECT is seen as sudden onset of marked confusion. It can occur either after the first ECT or not until after several sessions. Acute-onset delirium is usually severe and requires staff supervision. This delirium can be mistaken for catatonia, but ECT mitigates (not causes) catatonia. When acute delirium occurs after ECT, nonconvulsive status epilepticus should be considered and a standard neurological EEG checked. Although it is uncommon, its severity is a reason to routinely monitor the EEG during ECT for signs that the seizure has terminated[6].

Gradual cumulative disorientation is the ordinary form of ECT cognitive adverse effects. When it occurs, it is usually first noticeable after three or four ECT treatments and accumulates with additional ECT sessions. It is reflected by the decrease of Mini-Mental State Examination (MMSE) scores along the course of treatment. It varies among patients in both severity and duration, from negligible to substantial, and lasts up to a month. The largest and longest disorientations tend to occur in elderly patients and in patients with BT electrode placement[7].

Anterograde amnesia refers to difficulty in recalling information presented after ECT either because it has not been stored or access to the memory trace (the physical storage in the brain) is not available. Anterograde amnesia disappears most often within a few months following the end of the ECT course. However, a cumulative effect on memory exists during an ECT course, and severity of the impairment may increase with the number of treatments[8].

Retrograde amnesia is a loss of memory access to events that occurred, or information that was learned, before specific event (ECT). Retrograde amnesia can last for some time and may vary from a few hours to 2 years before the ECT session. Deficits in retrograde memory may involve public events and autobiographical memory (such as vacations and family gatherings)[9].

Amnestic effects seem greatest and most persistent for knowledge about the world (impersonal memory) compared with knowledge about self (personal memory). These deficits, more often partial, mostly concern events that occurred in the period close to the treatment. Explicit memory, associative memory, and visuospatial memory are also modified by ECT, whereas implicit memory, procedural memory, and semantic memory are not modified by ECT. Some periods of lacunar amnesia, defined by loss of memory of a specific event, can be permanent for events close to the ECT sessions[10].


  Materials and Methods Top


Search strategy

Only studies published since 1990 were reviewed. The severity of memory problems had been reduced by then because of the more common use of brief pulse wave ECT as an alternative to sine wave ECT, and also BF ECT has increased rate of use by then beside the traditional BT ECT. In total, eight psychological and medical databases (Medline, PubMed, Psych INFO, Science Direct, EMBASE, CINAHL, Cochrane, and Web of Knowledge). The following keywords were used in this search: (a) bifrontal, (b) bitemporal,(c) electrode placement, (d) ‘electroconvulsive’ (or ‘ECT’), and (e) cognitive impairment and cognitive subdomains (verbal memory-immediate recall, verbal memory-delayed recall, verbal memory-recognition, non-verbal memory immediate recall, non-verbal memory-delayed recall, non-verbal memory-recognition, working memory, attention, intellectual ability, executive function, processing speed, spatial problem solving, global cognitive status, language, visuospatial, autobiographical memory, and subjective memory).

The author then read each abstract to determine its relevance to the current review. All articles that considered investigating the cognitive impairment in BF and BT ECT were extracted for review, regardless of memory measures used.

Study selection

All the studies were independently assessed for inclusion. They were included if they fulfilled the following criteria.

  1. Published in English language
  2. Outcomes measured using standardized neuropsychological tests and self-report memory measures with established psychometric properties
  3. If a study had several publications on certain aspects, we used the latest publication giving the most relevant data.


Data extraction

If the studies did not fulfill the aforementioned criteria, they were excluded, such as studies comparing the efficacy of the two electrodes and studies not focused on cognitive adverse effects.

The analyzed publications were evaluated according to evidence-based medicine (EBM) criteria using the classification of the U.S. Preventive Services Task Force & UK National Health Service protocol for EBM in addition to the Evidence Pyramid.

The classification of the U.S. Preventive Services Task Force.

  1. Level I: evidence obtained from at least one properly designed randomized controlled trial
  2. Level II-1: evidence obtained from well-designed controlled trials without randomization
  3. Level II-2: evidence obtained from well-designed cohort or case–control analytic studies, preferably from more than one center or research group
  4. Level II-3: evidence obtained from multiple time series with or without the intervention. Dramatic results in uncontrolled trials might also be regarded as this type of evidence
  5. Level III: opinions of respected authorities, based on clinical experience, descriptive studies, or reports of expert committees.


Quality assessment

The quality of all the studies was assessed. Important factors included study design, attainment of ethical approval, evidence of a power calculation, specified eligibility criteria, appropriate controls, adequate information, and specified assessment measures. It was expected that confounding factors would be reported and controlled for and appropriate data analysis made in addition to an explanation of missing data.

Data synthesis

A structured systematic review was performed with the results tabulated.


  Results Top


Study selection and characteristics

In total, 45 potentially relevant publications were identified, and 22 articles were excluded as they did not meet our inclusion criteria. A total of 13 studies were included in the review as they were deemed eligible by fulfilling the inclusion criteria. Most studies examined the effects of ECT electrode position using MMSE. Some studies examined this effect using battery of cognitive tests. The studies were analyzed with respect to the study design using the classification of the U.S. Preventive Services Task Force & UK National Health Service protocol for EBM [Table 1].
Table 1: Studies investigating cognitive impairment in bifrontal and bitemporal electroconvulsive therapy

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Several studies show that unilateral electrode placement produces relatively fewer cognitive adverse effects during ECT. There are few reports comparing BF and BT placement electrode placements during ECT[2].

Cognitive adverse effects of bitemporal and bifrontal electroconvulsive therapy in patients with major depressive disorder according to evidence-based medicine

In the study by Lawson and colleagues, 40 patients experiencing a major depressive disorder, for whom ECT was clinically indicated, were assigned to one of three electrode placement groups: BT, RU, or BF. Comparisons of these groups in terms of cognitive status showed that the BF placement has advantage over BT placement. Lawson and colleagues explained the reason for such advantage was that BF electrodes avoided both temporal regions, and therefore spared both verbal and nonverbal functions. However, these differential effects, which were independent of the degree of clinical depression, were not evident 3 months after the last ECT[11].

This is consistent with the study by Letemendia and colleagues conducted in 1993, which examined cognitive adverse effects in 59 patients experiencing a major depressive episode, for whom ECT was clinically indicated. The patients were randomly assigned to one of three electrode placement groups for treatment with brief pulse, threshold-level ECT. Visual analog scale scores showed that the BF placement was superior to both BT and unilateral treatment. Letemendia et al.[12]. recommended using BF ECT as the first choice of electrode position in ECT regarding cognitive adverse effects profile.

These results were similar to that noted by Bailine and colleagues. Bailine and colleagues compared the clinical and cognitive effects of BF electrode placement with standard BT electrode placement in the treatment of patients with major depression. Standardized MMSEs were administered at baseline and repeated during the course of treatment. The standardized Mini-Mental State scores of the patients given BT ECT worsened more after treatment than did those of the patients given BF ECT. Bailine et al.[13] recommended further study of the two placements with more cognitive measures.

The study by Delva and colleagues agreed also with the previous results. In his study, patients with major depression were allocated blindly and randomly to receive BT, RU, or BF ECT, and cognitive effects were determined. There were substantial differences between the groups in mean charge per treatment, with the RU group receiving lower doses than either bilateral group. Cognitive impairment was related to electrical dose only in the BF group, which showed the least degree of treatment-induced intellectual dysfunction compared with BT or RU treatment; BF ECT yields the best ratio of benefits to side effects[14].

This is consistent also with a double-blinded parallel group study by Ranjkesh and colleagues, which evaluated the safety and efficacy of three ECT methods – moderate-dose BF, low-dose BT, and high-dose RU – in the treatment of a major depressive disorder. In eight-session ECT applications, cognitive outcome measures included assessment by Mini-Mental State. The three groups did not show any difference in baseline characteristics. There was a significant difference between standardized Mini-Mental State scores of patients in BF group compared with those in BT and RU groups, concluding that moderate-dose BF ECT revealed fewer cognitive adverse effects in comparison with BT and RU ECT[15].

This is confirmed by Systematic review and meta-analysis done by Dunne and McLoughlin on randomized controlled trials comparing efficacy and adverse effects of BF ECT to BT or RU ECT on depression. Cognitive outcomes were limited to MMSE in seven studies, with two studies measuring each of complex-figure delayed recall, trail-making tests, and verbal learning. Post-treatment cognitive decline was less for BF than BT ECT[16].

However, it disagrees with the Kellner and colleagues who failed to find substantial difference in cognitive effects of BF ECT and BT ECT in patients with major depressive disorder. This multicenter randomized, double-blind, controlled trial was carried out from 2001 to 2006. A total of 230 individuals with major depression and bipolar disorder were randomly assigned to one of three electrode placements during a course of ECT. The study by Kellner and colleagues was also unusual in that there were no consistent differences between cognitive effects of BT ECT and RU ECT too. Approximately 30–55% of the data on cognitive effects had to be imputed because of missing data in this study. Possible differential rates of dropout in those with worst cognitive effects could have resulted in failure to detect consistent differences in this outcome[17].

Cognitive adverse effects of bitemporal and bifrontal electroconvulsive therapy in patients with acute mania according to evidence-based medicine

Barekatain and colleagues conducted a parallel, double-blind, randomized clinical trial to compare safety of moderate-dose BF with low-dose BT ECT in the treatment of patients with severe mania. In total, 28 patients with severe mania were assigned randomly to moderate-dose BF and low-dose BT ECT. All patients received at least six sessions of ECT. The cognitive outcome measures included MMSE. Patients were evaluated 2 days after the third, sixth, and the last ECT sessions. Barekatain et al.[18] noted that the two groups did not show any difference in their baseline MMSE; however, there was a significant difference between the MMSE scores of the BF compared with the BT group after both the sixth ECT and final ECT treatments, with better cognitive performance for the BF group.

This disagreed with a double-blind randomized controlled study by Hiremani and colleagues which compared BF and BT ECT in acute mania. The patients in this study were randomized to receive BF or BT ECT. None of the patients were on mood stabilizers during the course of ECT. Cognitive functions were assessed eight hours after the fifth ECT session using the MMSE, Paired Associate Learning Test, Complex-Figure Test, Verbal Fluency Test (animals and fruits categories), and Trail-Making Test, Part A. There were no significant differences between the groups in performance on cognitive function tests. However, there are several limitations of the current study. First, the small sample size and high dropout rate restrict any conclusions regarding optimal electrode placement. Second, they were unable to elucidate exactly the reasons for dropouts or investigate any differences between patients who dropped out and completers. Third, valid cognitive assessments could be done only in a proportion (69%) of the patients, because some patients were still highly symptomatic at the scheduled time of assessment (end of the fifth ECT session) and were not cooperative for cognitive function tests. For the same reason, he could not administer the tests before starting ECT[19].

Cognitive adverse effects of bitemporal and bifrontal electroconvulsive therapy in patients with schizophrenia according to evidence-based medicine

Phutane and colleagues conducted a double-blind randomized controlled study comparing cognitive adverse effects of BF and BT ECT for schizophrenia. Patients who were prescribed ECT were randomized to receive ECT with either BF or BT placement. Their concomitant antipsychotic medications and the number of ECT sessions were not controlled. Cognitive tests were administered only once, on the day after their last ECT session, as the patients were too symptomatic to cooperate for detailed cognitive testing before the start of ECT course. Cognitive functions were assessed 24 h after the final ECT using a battery of tests. Hindi Mental Status Examination, PGI Memory Scale remote memory, recent memory, mental balance, attention and concentration, immediate and delayed recall, verbal retention for similar pairs, verbal retention for dissimilar pairs, visual retention, and visual recognition Color Trails Test (tests 1 and 2) were performed. This was used to measure sustained attention, sequencing and speed of processing, and spatial span test. This was used to measure spatial working memory and Controlled Oral Word Association. This was used to test verbal fluency. To examine if the frontal placement of electrodes could cause greater impairment in frontal lobe functions, Phutane and colleagues included cognitive tests involving the frontal lobe functions, in addition to tests of memory. BF ECT patients had significantly higher PGI Memory Scale total and total Hindi Mental Status Examination score than BT ECT patients; they also showed superior performance in other cognitive measures. There was no difference in remote memory, mental balance in alphabets and counting 20 backwards, verbal retention for similar pairs, visual retention components of PGI Memory Scale, and Color Trails Test. Phutane and colleagues explained the BF ECT's advantage over BT ECT is purportedly owing to the fact that it avoids direct electrical stimulation to the temporal lobes. However, it involves relatively higher stimulation of the frontal lobes. To examine if this would result in relatively more deficits in cognitive functions involving frontal lobes, they included the Color Trail Test, Spatial Span Test, and Controlled Oral Word Association Test. However, BF ECT patients performed better than BT ECT patients in most of these tests too. We considered two potential confounders for this cognitive advantage of BF ECT over BT ECT. (a) Severity of illness was lesser in BF ECT patients at the end of ECT course; this could have reflected on better performance on cognitive functions. (b) BF ECT patients had received fewer ECTs; number of ECTs had a profound influence on performance in cognitive function tests. Moreover, Phutane and colleagues conducted the cognitive assessments 1 day following the last ECT session; it is possible that acute confusional state following ECT could have confounded the performance on individual cognitive tests. BT ECT patients could have experienced greater confusion, and this could have potentially reflected their poorer performance on individual tests.

The advantages of study by Phutane and colleagues are the following: these potential patients referred for ECT were randomly assigned to receive either BF ECT or BT ECT; the raters were blind to the allotment status; allocation concealment was adhered to; dropouts were very few; and multiple dimensions of outcome, including cognitive functions, were assessed. There were no differences between the groups in sociodemographic details. The groups were comparable on duration of illness, indication for ECT, baseline severity, and concomitant medications. Thus, the group differences are truly reflective of the advantage of BF ECT over BT ECT and not of any confounding factors[20].

Cognitive adverse effects of bitemporal and bifrontal electroconvulsive therapy in patients with heterogeneous psychiatric diagnoses according to evidence-based medicine

The retrospective study by Viswanath and colleagues studied the records of all patients referred for ECT between the months of August 2008 and July 2010. In total, 105 of these patients had received BF ECT. These records were compared with the records of 105 patients who received BT ECT. For each patient who received BF ECT, the very next person posted for BT ECT was taken as the control.

Although BF ECT patients also had a significantly higher seizure threshold, they showed fewer cognitive adverse effects[21].

This is consistent with earlier retrospective study by Bakewell and colleagues which compares the adverse effects of BT and BF electrode placement in a community hospital setting. The medical records of 76 patients receiving ECT treatments from 1994 to 2000 were reviewed to extract data on the characteristics of the course of ECT and documentation of confusion, disorientation, and memory loss. Bakewell et al.[22] found that the BT placement caused significantly more cognitive impairment.


  Discussion Top


Research into the different technique of practicing ECT is a major concern since its launching in 1938. Recently, the area of associated cognitive adverse effects and how to limit them have gained much interest, in which there are a significant number of scientific studies being investigated.

Reviewing the recent studies about comparing cognitive adverse effects of BF and BT ECT in patients with major depressive disorder, we found that BF ECT has been associated with less cognitive effects and showed early recovery than BT ECT. Also on reviewing the recent studies about comparing cognitive adverse effects of BF and BT ECT in patients with schizophrenia, we found that BF ECT has better cognitive profile than BT ECT. Finally, on reviewing the recent studies about comparing cognitive adverse effects of BF and BT ECT in patients with acute mania, we found that regarding efficacy, which had not been included in our research, BF ECT has been associated with less cognitive effects and showed early recovery than BT ECT. However, some authors found no difference in both groups.

The research conducted on cognitive impairment from BF ECT has been inadequate owing to the use of nonspecific cognitive measures (such as MMSE) or an inordinate focus on memory functioning (which is believed to be mostly subsumed in the temporal lobes). Because BF ECT increases cerebral blood flow in the frontal lobes more intensely than either of the other placements, research must instead focus on investigating the possible effects of BF ECT on executive functioning, which is believed to be subsumed in the frontal lobes. This is especially important because of the increasing popularity of BF ECT.

The sensitivity of objective memory measures, such as the MMSE, has been questioned. This test may be insensitive to ECT-induced cognitive effects because of a large number of items within the assessment, focusing primarily on very old events, rather than on events occurring closer to ECT.

Another issue associated with studies of cognitive impairment after ECT is the lack of research considering premorbid cognitive status. Much of the research conducted compares assessment scores before ECT, when the patient's level of illness is at its highest, to performance after ECT, when illness is often improved. Such assessments give no indication of ‘normal’ premorbid memory functioning before, and therefore, improvements in performance on cognitive measures observed at follow-up could be attributed to improvement of symptoms. Therefore, further research needs to be conducted to obtain information about the individual's memory performance before illness.

It is further important to assess memory at different times after ECT. Tests of autobiographical memory conducted immediately after treatment could paradoxically result in an overestimate of the patient's ability. This is because memory problems may only become apparent to the individual at a later date, once they have left hospital and are attempting to function in everyday life. This indicates the value of follow-up, particularly after longer periods after ECT.


  Conclusion Top


The paper reviews all studies on BF and BT ECT which used at least one instrument for cognitive assessment before and after ECT. The results indicate more loss of autobiographical memory, executive functions, and impairment of verbal fluency in BT ECT patients than those undergoing BF ECT, especially in patients with major depressive disorder and schizophrenia. Based on the included studies, the results suggest that BF ECT causes fewer declines in cognitive functions after ECT than BT ECT.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

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