Does Criticism of Electroconvulsive Therapy undermines its benefits: A Critical Review of its Cognitive Adverse Effects

Commentary Does Criticism of Electroconvulsive Therapy undermines its benefits: A Critical Review of its Cognitive Adverse Effects A Rajendran, 1 VS Grewal, 2 Jyoti Prakash 3 1 Department of Psychiatry, Assam Rifle Composite Hospital, Shokhuvi-797115 2 Department of Community Medicine, Armed Forces Medical College, Pune-411040 3 Department of Psychiatry, Command Hospital Eastern Command, Kolkata-700027 Contact: Jyoti Prakash, Email: drjyotiprakashpsy@yahoo.com Introduction Convulsive therapy for major psychiatric illnesses is in use since around fifteenth century 1, 2. Electrically induced seizures or Electroconvulsive therapy (ECT) was introduced in 1938 by Lucio Cerletti and Ugo Bini. Electroconvulsive therapy is an effective therapy for a variety of psychiatric disorders which includes severe depression, acute psychosis and suicidal patients and is known to be quicker compared to other modes. It is considered the most effective antidepressant treatment, with medication resistance its leading indication. 85% patients receiving ECT have major depression as diagnosis. 3 Though there is inadequate evidence to suggest that ECT causes brain damage and it is aptly known that the ECT in fact stimulates neuroplasticity; use of electricity to, trigger a seizure has held the treatment with criticism despite decades of its successful use. 4 Electroconvulsive therapy and cognitive deficits Recently considerable research have been done to validate the efficacy and safety of ECT; as well as; in the improvements of current ECT techniques, equipment or standards. 5-10 There have been conflicting accounts of severity and duration of memory and other cognitive difficulties. 1,11-14 Acute disorientation following treatments has been well documented but are usually brief. Extent of short-term and long-term cognitive deficits remains controversial. Meta-analysis and systematic reviews have differed in the categorization of side effects in terms of time after ECT as acute, subacute and long term. Period of manifestation of acute effects have been mentioned from 24 hours in some reviews to 3 days after last ECT in others. According to a systematic review, differences in ECT modalities may account for variations in cognitive impairment, with bilateral ECT method producing greater deficits than the unilateral, thrice weekly treatment more than the twice weekly and high-dose ECT more than the low-dose ECT. 7 As for long-term side effects, reviews agree that after 6 months no deficits persist. 15-17 No significant differences have been noted between real or simulated ECT, between sine-wave or brief-pulse ECT, 7 or between ECT or pharmacotherapy. 15 Cognitive impairment post ECT can be divided intoimpairment in orientation immediately following ECT administration and anterograde/retrograde memory changes that may follow ECT and may around six months. There is limited albeit conflicting evidence that the effects of ECT on memory and cognitive function may not last more than six months. 18 According to Pascal Sienaert, 19 post ECT patients can experience difficulties in ability to acquire and retain new information (anterograde memory impairment) which mostly recover to baseline by 1 month. Retrograde amnesia (inability to recall past events and information learned) 160

APRIL 2015 DELHI PSYCHIATRY JOURNAL Vol. 18 No. 1 reported especially after bilateral ECT are relatively short lived (less than 6 months post-treatment). Nature and extent of retrograde memory impairment often remains to be systematically examined. A recent review has shown that the use of a stimulus with ultra-brief pulse (0.3 milliseconds) produced no deterioration in cognitive measures. However, patients needed additional treatment sessions to achieve results comparable to those achieved with the standard pulse ECT. As there is lack of Randomised Controlled Trials (RCTs) utilizing appropriate standardized scale, comparison groups and sufficient reporting of results; meta-analyses could only be conducted in three domains: time to reorientation, global cognition (MMSE), and retrograde autobiographical memory (AMI). Additionally, a meta-analysis was conducted of non-randomized data (reported within RCTs) which compared the change in AMI pre-treatment and post-treatment. 18 Conclusions drawn are described below. 1. Time to reorientation: Bilateral ECT was associated with longer disorientation than the right unilateral, left unilateral, or unilateral non-dominant electrode placement. There was also evidence to suggest that bifrontal ECT is associated with longer periods of disorientation than the bitemporal ECT..There was no evidence that the disorientation following ECT is long-term or persistent. Metaanalysis revealed that the electrode placement significantly affected time to reorientation in bilateral more than unilateral, increasing it by 18 seconds (unilateral medium vs. bilateral low) to 29 seconds (unilateral low vs. bilateral high). It implied that patients receiving bilateral ECT at high doses had around 29-second longer time to reorientation compared to those receiving unilateral low dose ECT.. Effect of energy level seemed less relevant than the electrode placement. 2. Executive function: Data suggest no significant change immediately following ECT from baseline. Evidence that bilateral ECT is associated with greater executive dysfunction than the unilateral ECT is inconclusive. Differences were not found between bifrontal and bitemporal ECT. Brief pulse ECT showed larger acute executive dysfunction than the ultrabrief pulse. There was limited evidence that the sine wave stimulation was not significantly different from pulse wave or the high energy from low energy. One study suggested left unilateral ECT to be associated with greater executive dysfunction than the right unilateral. 3. Global Cognitive Function: There is limited evidence to suggest that bilateral ECT is significantly worse than unilateral ECT immediately post ECT. Sub-acutely there was limited evidence of bitemporal ECT being worse than bifrontal ECT. Results were equivocal regarding electrode placement, difference in energy dose and change from baseline in the global cognitive function. In medium term, no differences in global cognitive function were seen between ultrabrief pulse bifrontal and ultrabrief pulse unilateral ECT; both modalities were seen associated with improvement from baseline at six weeks. On longer-term effects, evidence suggested either improvement or no change in global cognitive function from baseline. Meta-analysis demonstrated that immediately post-ect, the bilateral ECT was associated with around 10% worse MMSE scores than the unilateral. There was no statistical difference in unilateral electrode placement with low energy compared to the medium energy or in the bilateral electrode placement comparing low energy to the high energy. Disparity continued (and increased) at two months post-ect. Patients receiving bilateral high dose ECT had around 12% worse performance on MMSE compared to unilateral low dose ECT. 4. Global Memory: Data regarding changes in global memory immediately following the treatment are limited. In sub-acute period, no significant differences were seen between unilateral and bilateral electrode placement, or high versus low dose energy dosage. Results were equivocal regarding change from baseline. For medium term, limited evidence was there that the bilateral ECT thrice weekly was associated with significantly more global memory loss than twice weekly..no data existed on difference between electrode placement, waveforms and energy dose. At six months, limited data suggested that there was no significant difference in global memory between ECT and sham, and change from baseline to six months. 5. Anterograde Verbal: There were equivocal findings regarding verbal anterograde memory impairment in studies comparing effect of ECT vs. sham ECT. Literature suggested sine wave ECT when compared with brief pulse ECT; had greater 161

anterograde verbal memory impairment. A week following ECT therapy, verbal memory function following right unilateral electrode placement and low/moderate energy dose ECT may return to baseline and might even improve. 2 weeks after ECT therapy, verbal memory function following bilateral electrode placement may return to baseline and might improve. Finally at 6 months of ECT, no differences were present between ECT and sham ECT or between bilateral and unilateral nondominant hemisphere electrode placement. 6. Anterograde Non-verbal: Immediately post-ect, ECT was associated with more decline than the sham. Though there were no differences with respect to electrode placement; brief pulse may be worse than the ultrabrief pulse. Subacutely, no differences were noted among any ECT treatment parameters. Two weeks post-ect, there was inconclusive evidence to support any differences among ECT treatment parameters with regards to decline. Conclusive evidence suggested that there was no change from baseline. 7. Retrograde Impersonal Memory: Immediately following ECT, the data appeared equivocal regarding changes. One study suggested poorer retrograde impersonal memory with sham treatment compared to ECT; which improved eight hours following treatment in both the groups. Some evidence suggest that bilateral placement resulted in poorer performance compared to unilateral. Subacutely, equivocal evidence suggested impairment with respect to electrode placement, pulse or energy dose. For medium term, there were equivocal findings among ECT treatment parameters. In one study, bilateral (not unilateral) group showed significant improvement in retrograde impersonal memory from baseline. There were no studies on retrograde impersonal memory from three to less than six months following ECT. At six months, there were no differences seen between ECT and sham ECT, electrode placement or pulse wave. Data did not show a significant change at six months compared to baseline. 8. Retrograde Personal (Autobiographical) Memory: Immediately post ECT, limited evidence suggested that bilateral electrode placement had greater impairment. ECT was associated with decline in autobiographical memory immediately post-ect (compared with baseline). Sub-acutely, conclusive evidence supported the finding that the bilateral ECT had greater impairment compared to unilateral, right unilateral or unilateral non-dominant ECT samples. Limited evidence were to suggest sine wave ECT to be worse compared to brief pulse ECT and high energy dose ECT worse than the low energy dose ECT. There was decline from baseline with ECT (except for ultrabrief pulse stimulus which did not show significant change from baseline). For the medium term (2 weeks to less than 3 months), there were limited data towards the effects of electrode placement, pulse or energy dose. Studies reviewed appear to suggest no significant differences with respect to treatment parameters. Additionally, there were limited data with respect to change from baseline suggesting no change. At three months, limited studies yielded conflicting results. At six-month time period one study examines autobiographical memory, comparing pre- ECT course scores with that of post-ect. Scores improved since the three-month time period. 9. Subjective Memory: Several methodological issues were there with regard to use of selfreported, subjective complaints of memory impairment. These relied heavily on self-report scales and were highly dependent on the time these scales were completed. Subjective reports of memory impairment may be associated with degree to which the depressive symptoms resolve. Patients in general, were more likely to report memory impairment immediately after ECT. There were no randomized trials on subjective memory within first 24 hours of ECT. Sub-acutely, sufficient data conclude that bilateral ECT is associated with more subjective memory complaints than the unilateral. In terms of change from baseline, strong evidence suggest that the subjective memory did improve after a course of ECT. Medium term study reported no difference between unilateral and bilateral ECT at one month. There were limited data on function at six months. Overall, no difference appeared to be there in subjective memory assessment between ECT and sham, or any ECT treatment factors. Some evidence do show improvement or no change in subjective memory compared to the baseline. Semkovska and colleagues 20 conducted a metaanalysis of unilateral ECT effects on cognitive performance relative to: (a) bitemporal electrode placement, (b) electrical dosage, and (c) time interval 162

APRIL 2015 DELHI PSYCHIATRY JOURNAL Vol. 18 No. 1 between final treatment and cognitive reassessment. Thirty-nine studies (1415 patients) were included. Primary findings indicated that up to three days after the final treatment, unilateral ECT was associated with significantly smaller decreases in the global cognition, delayed verbal memory retrieval, and autobiographical memory, vis-a-vis bitemporal ECT. Higher electrical dosage led to larger decreases in verbal learning, visual recognition, delayed verbal memory retrieval, and semantic memory retrieval. Retested more than three days after completing ECT, no significant differences did remain between the two electrode placements. Hihn et al. 21 assessed twenty severely depressed, drug-treatment resistant, elderly patients with Wechsler Memory Scale-Revised (WMS-R) before and at the end of the ECT series. It was seen that Prefrontal cortex-related memory processes, especially immediate memory encoding, improved after the ECT. Long-term memory on the other end remained impaired, indicating that severely depressed patients do remain cognitively inferior to the normal subjects despite a clinically successful treatment. Thus there appear a lack of consensus in the literature as to whether number of ECT s or Dose of ECT, whether unilateral or bilateral ECT (given equivalent efficacy), regarding subtypes of memory which are affected by ECT and if affected as to how long they last. In addition these studies used a variety of scales, with each of these scales having their own plethora of subtests thereby making it difficult to arrive at a prudent consensus. These have been aptly brought out by the various review articles and meta-analysis. 3,18 Studies in general have dampened the undue curiosity, chaos or criticism which abounds the use of ECT; thus indirectly highlighting the merit or the advantage of the therapy called Electroconvulsive therapy. A review of the psychiatric literature on ECT over the past seven decades illustrates that, the issue of memory and ECT is much more complicated than just one of inside versus outside profession, scientific findings vis-a-vis subjective complaints and propsychiatry versus anti-psychiatry. 22-23 Conclusions ECT promises to be an effective therapeutic modality regardless of the controversies surrounding its use. Adverse cognitive effects debated have not found it solid footings in the evidence of literature; thereby it should, in no way, undermine the significant therapeutic benefit ECT has. References 1. Hirshbein L. Historical Essay: Electroconvulsive Therapy, Memory, and Self in America. J History Neurosci 2012; 21 : 147 169. 2. Abrams R. The mortality rate with ECT. Convuls Ther 1997; 13(3) : 125-7. 3. Semkovska M, McLoughlin DM. Objective Cognitive Performance Associated with Electroconvulsive Therapy for Depression: A Systematic Review and Meta-Analysis. Biol Psychiatry 2010; 68 : 568 577. 4. American Psychiatric Association Task Force on Electroconvulsive Therapy. The Practice of Electroconvulsive Therapy: Recommendations for Treatment, Training, and Privileging. Washington, DC: American Psychiatric Association, 2001. 5. Sharma V. The effect of electroconvulsive therapy on suicide risk in patients with mood disorders. Can J Psychiatry 2001; 46(8) : 704-9. 6. Chung KF. Relationships between seizure duration and seizure threshold and stimulus dosage at electroconvulsive therapy: implications for electroconvulsive therapy practice. Psychiatry Clin Neurosci 2002 Oct; 56(5) : 521-6. 7. UK ECT Review Group. Efficacy and safety of electroconvulsive therapy in depressive disorders: a systematic review and metaanalysis. Lancet 2003; 361(9360) : 799-808. 8. Prudic J, Olfson M, Marcus SC, Fuller RB, Sackeim HA. Effectiveness of electroconvulsive therapy in community settings. Biol Psychiatry 2004; 55(3) : 301-12. 9. Merkl A, Schubert F, Quante A, Luborzewski A, Brakemeier EL, Grimm S, Heuser I, Bajbouj M. Abnormal cingulate and prefrontal cortical neurochemistry in major depression after electroconvulsive therapy. Biol Psychiatry 2011; 69(8) : 772-9. 10. Phutane VH, Thirthalli J, Muralidharan K, Naveen Kumar C, Keshav Kumar J, Gangadhar BN. Double-blind randomized controlled study showing symptomatic and cognitive superiority 163

of bifrontal over bitemporal electrode placement during electroconvulsive therapy for schizophrenia, Brain Stimul 2012. 11. Squire LR, Slater PC. Electroconvulsive therapy and complaints of memory dysfunction: a prospective three year followup study. Br J Psychiatry 1983; 142 : 1-8. 12. Weeks D, Freeman CP, Kendell RE. ECT: III: Enduring cognitive deficits? Br J Psychiatry 1980; 137 : 26-37. 13. Lisanby SH, Maddox JH, Prudic J, Devanand DP, Sackeim HA. The Effects of Electroconvulsive Therapy on Memory of Autobiographical and Public Events. Arch Gen Psychiatry 2000; 57(6) : 581-90. 14. Brodaty H, Berle D, Hickie I, Mason C. Side effects of ECT are mainly depressive phenomena and are independent of age. J Affect Disord 2001; 66(2-3) : 237-45. 15. Calev A. Neuropsychology and ECT: past and future research trends. Psychopharmacol Bull 1994; 30(3) : 461-9. 16. Lisanby SH, Luber B, Schlaepfer TE, Sackeim HA. Safety and feasibility of magnetic seizure therapy (MST) in major depression: Randomized within-subject comparison with electroconvulsive therapy. Neuropsychopharmacology 2003; 28(10) : 1852-65. 17. Ingram A, Saling MM, Schweitzer I. Cognitive side effects of brief pulse electroconvulsive therapy: A review. J ECT 2008; 24(1) : 3-9. 18. United States Food and Drug Administration. Executive Summary: Meeting to Discuss the Classification of Electroconvulsive Therapy Devices (ECT). Meeting of the Neurological Devices Panel, 2011. 19. Pascal Sienaert. What We Have Learned About Electroconvulsive Therapy and Its Relevance for the Practising Psychiatrist. Can J Psychiatry 2011; 56(1) : 5 12 20. Semkovska M, Keane D, Babalola O, McLoughlin DM. Unilateral brief-pulse electroconvulsive therapy and cognition: Effects of electrode placement, stimulus dosage and time J Psychiatr Res 2011; 45(6) : 770-80. 21. Hihn H, Baune BT, Michael N, Markowitsch H, Arolt V, Pfleiderer B. Memory Performance in Severely Depressed Patients Treated by Electroconvulsive Therapy. J ECT 2006; 22(3) : 189-95. 22. Beaudreau SA, Finger S. Medical electricity and madness in the 18th century: the legacies of Benjamin Franklin and Jan Ingenhousz. Perspect Biol Med. 2006; 49(3) : 330-45. 23. Finger S, Zaromb F. Benjamin Franklin and shock-induced amnesia. Am Psychol 2006; 61(3) : 240-8. 164