November 2011  << Back  

  Can't open the PDF? Click here for help.

 

 RESEARCH ARTICLE

Clinically insubstantial cognitive side effects of bitemporal electroconvulsive therapy at 0.5 msec pulse width

Ronald L. Warnell, MD

Department of Psychiatry, Loma Linda University, Loma Linda, CA, USA

Conrad M. Swartz, PhD, MD

Department of Psychiatry, Oregon Health and Science University, Portland, OR, USA, Department of Psychiatry, Southern Illinois University School of Medicine, Springfield, IL, USA

Alice Thomson, MA, PhD

Department of Psychology, Loma Linda University, Loma Linda CA, USA

BACKGROUND: We measured cognitive side effects from bitemporal electroconvulsive therapy (ECT) using stimuli of 0.5 msec pulse width 900 milliamperes (mA).

METHODS: Mini-Mental State Exam (MMSE) and 21-item Hamilton Rating Scale for Depression (HRSD-21) were rated within 36 hours before and 36 hours after a series of 6 bitemporal ECT sessions on 15 patients age ≥45.

RESULTS: MMSE remained high after ECT (pre-ECT mean 29, standard deviation [SD] 1.60, post-ECT mean 28.53, SD 1.36) with no significant change. The mean HRSD-21 fell from 27.5 to 16.3. Post-ECT MMSE was significantly and markedly higher than in previous studies of bitemporal ECT; all had used ECT stimuli of pulse width at least 1 msec.

CONCLUSIONS: With stimuli of 0.5 msec pulse width and 900 mA, 6 bitemporal ECTs did not decrease MMSE score. This result leaves no opportunity for further decrease in basic cognitive side effects, and complements published reports of stronger physiological effects with stimuli of 0.5 msec pulse width and 900 mA. ECT stimuli of 0.5 msec pulse width and 900 mA are more desirable than wider pulse widths. Six bitemporal ECT sessions using these stimuli generally will not have more cognitive side effects than treatments with other placements, allowing maintenance of full efficacy with clinically insubstantial side effects.

KEYWORDS: electroconvulsive therapy, cognitive aspects, bitemporal

ANNALS OF CLINICAL PSYCHIATRY 2011;23(4):257-262

  INTRODUCTION

Despite reliably providing full remission from psychotic, melancholic, and catatonic depressive subtypes, electroconvulsive therapy (ECT) is underused and essentially unavailable in many locations. Minimizing cognitive effects is vital because patient and clinician anxiety about these effects may contribute to ECT underuse, although any adverse effects occur primarily during and shortly after treatments. Even temporary confusion should be minimized because it can be unpleasant and stigmatizing. The clinical rationale for ECT is quick efficacy, which must be preserved.

Three methods have been used to mitigate cognitive side effects from ECT: using brief pulse stimuli, avoiding excessive stimulus doses and ECT sessions, and electrode placement. Brief pulse stimuli of 1 to 2 msecs pulse width showed substantially lower side effects than wide phase (8.3 msec pulse width) sine wave stimuli with the same electrode placement.1 These side effects may be related to the broad width of the wave phase (pulse) rather than the shape of the electrical wave.2 No other electrode placement is more effective than bitemporal or produces more side effects, but all reported studies of side effects from brief pulse stimuli involved pulse widths of at least 1 msec.3,4 In several studies, the Mini-Mental State Exam (MMSE) score was used to reflect basic cognitive functioning.5,6

We present an initial report of MMSE testing during a course of 0.5 msec pulse width bitemporal ECT. We chose this pulse width because it appears to have the greatest efficiency and physiological activity, and greater efficiency suggests fewer side effects.1 Shortening the pulse width from 1 to 2 msec to 0.5 msec can be considered an extension of changing from wide phase sine wave stimuli to 1 to 2 msec pulse stimuli.

  METHODS

Twenty patients who gave informed consent to the institutional review board-approved protocol were recruited from all patients age ≥45 referred to a university ECT service who met DSM-IV-TR criteria for nonpsychotic major depressive disorder, per evaluations by psychiatrists. One investigator (R.W.) interviewed all patients. Patients with preexisting cognitive impairment, anticonvulsant medication use, or an interfering medical condition (eg, coarse brain disease) were excluded from the study. As part of a concurrent study previously reported, all patients were randomized to either standard ECT procedure or the same procedure with propofol interruption of seizure.7 Fifteen hospitalized patients completed the study course of 6 ECT sessions (mean age 57.8, standard deviation [SD] 8.2); 1 never received ECT, 2 discontinued before the sixth ECT session, and 2 were disqualified for receiving midazolam for postictal agitation.

All treatments were performed with bitemporal electrode placement using a Thymatron System IV instrument (Somatics LLC, Lake Bluff, IL). Anesthesia initially consisted of IV atropine, 0.4 mg, etomidate, 0.2 mg/kg, and succinylcholine, 1 mg/kg. Propofol interruption patients also received propofol, 0.5 mg/kg, infused 15 seconds post-seizure during each ECT session. Seizure threshold was measured at the first ECT session, and stimulus charge was increased as needed to maintain electroencephalogram (EEG) seizure duration at least 25 seconds. Stimuli were 0.5 msec pulse width and 900 milliamperes (mA) current; frequency ranged from 10 to 70 hertz (Hz) (mean 31.5 Hz). Mean charge was 192.5 millicoulombs (mC) at 900 mA; this is two-thirds of age, a high dose for bitemporal ECT.8 ECT was administered in 6 separate sessions, 3 times a week. Patients who clinically required additional ECT treatment continued receiving treatment outside the study, averaging 4.5 additional sessions. EEG was recorded with bilateral frontal-mastoid placement. The MMSE and the 21-item Hamilton Rating Scale for Depression (HRSD-21) were administered within 36 hours before the first ECT session and within 36 hours after the sixth ECT session by an investigator (A.T.).9

We searched the medical literature for all reports of MMSE ratings made within 5 days of ≥4 ECT sessions or a completed course of ECT. Because cognitive side effects typically fade quickly after ECT, we did not include studies that rated post-ECT MMSE scores >5 days after treatment. For comparisons we recorded electrode placements, numbers of treatments, mean patient age, numbers of patients, and means and SD of post-ECT MMSE scores.

  RESULTS

Patients’ mean MMSE scores were approximately the same pre-ECT (29.00, SD 1.60) and post-ECT (28.53, SD 1.36). The pre-post MMSE difference (mean 0.47, SD 1.30) was not significantly different from zero (t = 1.39, P > .10). Post-ECT MMSE scores were 26 to 30. There was no difference in MMSE score between the standard treatment and propofol interruption groups and no significant difference in stimulus charge, HRSD-21, or number of ECT treatments received (mean 10.5); therefore, these 2 groups were combined. HRSD-21 fell significantly, from 27.5 (SD 5.01) pre-ECT to 16.3 (SD 5.24) after 6 ECT sessions (P < .01), reflecting antidepressant effect.

TABLE 1 lists all studies reporting post-bitemporal ECT MMSE within 5 days after ≥6 ECT sessions. Post-ECT MMSE in the present study is significantly higher than each of the previous studies; the highest previously reported MMSE score is 25.7.6 One report was disqualified for excluding patients with excessive cognitive side effects, thereby artificially raising the post-ECT mean MMSE.10

In our study, variance in MMSE scores was lower than for every other reported study of bitemporal ECT in major depressive disorder. Therefore, our present post-ECT MMSE scores were uniformly near the mean of 28.5 and varied less than was reported at wider pulse widths. The single report with similarly low variance in MMSE scores studied younger patients (mean age 27.4) with severe mania.11 The variance suggests that with 0.5 msec pulse width, 1 patient in 40 should show post-ECT MMSE <26. Larger variances at wider pulse widths indicate that these pulse widths are accompanied by MMSE scores much further below the mean; for example, 3 of 20 patients MMSE <17,12 2 of 12 patients MMSE <15,13 and 4 of 24 patients MMSE <21.6


TABLE 1

Other reports of MMSE scores within 5 days after bitemporal ECT

  Pulse width (msec) Post-ECT MMSE mean, (SD) Number of ECT sessions Number of patients Patient age, mean Diagnosis Significance of difference in mean (t, df, P) Significance of difference in variance (F, df, P)
Bailine et al, 20006 ≥1 25.7 (4.6) 5.7 24 56 Depression t = 2.31, df = 37, P = .03 F = 11.5, df = 23,14, P < .01
Bareketain et al, 200811 1 25.2 (1.3) 6 14 27.4 Mania t = 6.73, df = 27, P < .01 F = 0.9, df = 13,14, P = NS
Ranjkesh et al, 200521 1 21.3 (3.6) 8 14 33.4 Depression t = 7.25, df = 27, P < .01 F = 7.0, df = 13,14, P < .01
Sackeim et al, 200012 1.5 <23.3 (6.5)a 6 20 56 Depression t = 2.77, df = 33, P < .01 F = 25, df = 19,14, P < .01
Stoppe et al, 200613 1 18.9 (4.8) 4 and 8 12 75 Depression t = 7.44, df = 25, P < .01 F = 12.4, df = 11,14, P < .01
amodified MMSE of maximum score 57 multiplied by 30/57 to obtain comparable numbers. Statistical comparison is of pre-post MMSE differences, their mean 5.2, SD 6.5. Post-ECT MMSE assumes pre-ECT MMSE <28.5.
ECT: electroconvulsive therapy; MMSE: Mini-Mental State Exam; NS: not significant; SD: standard deviation.

  DISCUSSION

The only unusual aspect of our method was 0.5 msec pulse width, which seems to explain the lack of decline in MMSE score with bitemporal ECT. The extraordinarily high post-ECT MMSE (mean 28.5) leaves no opportunity for substantial improvement, which surprised us. Our exclusion of patients age <45 (mean age 57.8) and the generous stimulus doses used suggest robustness of this finding. This is because brief-pulse ECT cognitive side effects increase with age and stimulus dose, and MMSE scores decrease with age.6,12,14 We chose etomidate for anesthesia because it has no intrinsic anticonvulsant activity—unlike propofol and barbiturates—and should not inhibit development of cognitive side effects.

Although our study did not compare different pulse widths, the present MMSE results can be compared with those in other studies of electrode placement because of the objective, impartial nature of MMSE scoring. In contrast, studies of therapeutic benefit involving impressionistic ratings require blinded controls to achieve impartiality. Moreover, our results should generalize to typical ECT patients and be suitable for comparing MMSE scores in other ECT studies because our patients were typical of ECT patients. Our patients had private insurance or Medicare, were acutely depressed, were not young, and were not chronically disabled. The only identifiable reason for the lack of reduction in MMSE score is the 0.5-msec pulse width stimuli.

Although the MMSE is a not a complete assessment of cognitive functioning, it is widely used in clinical and research settings because the score is useful. Scores of ≥28 correspond to no substantial cognitive impairment and scores of ≤24 are associated with cognitive difficulties.5 Insofar as the MMSE is clinically useful, so is the present result.

We could find no previous study of cognitive effects during or shortly after ECT using 0.5-msec pulse width stimuli with any electrode placement. One case report described an absence of ECT cognitive side effects in an 81-year-old woman with incipient Alzheimer’s disease.15 The authors attributed this absence of cognitive side effects to low-dose rivastigmine, but all ECT sessions were given with 0.5 msec pulse width and 900 mA stimuli. Earlier studies demonstrated that 0.5-msec pulse width stimuli have stronger seizure-inducing and physiological effects than 1-msec pulse width stimuli of the same charge, but cognitive effects were not studied.8,16 The greater efficiency of 0.5-msec pulse width stimuli in those studies suggests a simple explanation of less cognitive effects. With less efficient stimuli, the dose that is in excess of the most efficient stimulus presumably interferes with seizure induction and unwanted effects. The greater efficiency of shorter phase width presumably explains the fewer cognitive side effects of brief pulse stimuli (1 to 2 msec) than wide phase sine wave stimuli (eg, 50 or 60 Hz with corresponding phase width 10 or 8.3 msec).

Our results suggest that 0.5 msec pulse width is a desirable ECT stimulus because it has less severe cognitive side effects and greater efficiency in inducing seizure and physiological changes than wider pulse widths. In contrast, recent reports about 0.3- to 0.37-msec pulse width ultra-brief stimuli suggest clinical unreliability and low efficacy. Loo et al achieved remission in 13% of 30 patients receiving right-unilateral ECT with ultra-brief stimuli of 0.3 to 0.37 msec pulse width at 800 mA, despite averaging 12 ECT sessions per patient.17 Data collected by Sackeim et al are peculiar because they describe greater effectiveness of right-unilateral ECT than bitemporal ECT using the same stimuli.18 This conflicts with basic concepts that bitemporal ECT has the highest efficacy and that there is no rationale for another placement to have higher efficacy, unless the bitemporal ECT method studied was underdosed or otherwise impaired. At another medical center using these same ultra-brief stimuli, the clinical effectiveness of unilateral ECT was judged distinctly inadequate.19 Because no study has compared stimuli of 0.3 to 0.37 msec pulse width against 0.5 msec pulse width, there is no justification for clinically preferring 0.3 to 0.37 msec pulse width to 0.5 msec pulse width or for disregarding the reported deficiencies in effectiveness of 0.3 to 0.37 msec pulse width at 800 mA current.

The differences between 0.5-msec, 900-mA pulses and 0.3- to 0.37-msec, 800-mA pulses appear substantial. A stimulus pulse of 0.5 msec at 900 mA has 1.9 times the charge and at least 2.7 times the dose of a 0.3-msec, 800-mA pulse and 1.5 times the charge and at least 2.1 times the dose of a 0.37-msec, 800-mA pulse, based on a rational physiologic formulation of ECT dose. Moreover, ultra-brief pulses penetrate the brain more shallowly, therefore seizure generation is not as well generalized through the brain; this weakness presumably underlies their lower and less reliable effectiveness.2

The low side effects of bitemporal 0.5 msec pulse width stimuli may be more difficult to observe with other electrode placements because post-ECT MMSE scores can range higher, even at wider pulse widths. TABLE 2 lists the highest and lowest reported values we could find of post-ECT MMSE with the other modern ECT electrode placements: left-anterior right temporal (LART), bifrontal, and right-unilateral.3 Post-ECT MMSE averaged 28.4 with LART, and mean scores ranged from 24.1 to 28.1 with bifrontal placement.6,20,21 MMSE means ranged from 22.2 to 28.3 after a course of right unilateral ECT.21,22 Presumably, these 3 placements will show less cognitive effects than bitemporal placement at 0.5 msec pulse width, but evidence may require studying older patients and longer ECT courses.

The mean charge of 192.5 mC was on average one-third higher than suggested by the half-age initial dosing method for bilateral ECT. This suggests that dosing bilateral ECT by the half-age method is not overdosing. It also is not underdosing because of its 92% success rate for inducing seizures at ECT sessions 1 through 5 with 0.5 msec pulse width.8 A statistical power analysis would not lead to additional interpretations of our data because there was no trend for the MMSE score to fall with ECT; the absence of a trend implies that an infinite patient sample is needed to prove a difference. Still, our patient sample is small and definitive proof should involve replications in larger groups of patients.

It has long been supposed that electrode placement has a stronger influence on cognitive side effects than pulse width does.3 The results of our study suggest this supposition does not always hold. A recent report suggested that ECT side effects are not dependent on electrode placement.4


TABLE 2

Highest and lowest post-ECT MMSE scores with other electrode placements

  Pulse width (msec) Electrode placement Post-ECT MMSE Number of ECT sessions Number of patients Patient age, mean Diagnosis
Swartz, 199420 1 LART 28.4 8.5 10 54.2 Depression (5), mania (2), mixed (3)
Ranjkesh et al, 200521 1 BF 24.1 8 13 36.7 Depression
Bailine et al, 20006 ≥1 BF 28.1 5.9 24 49.6 Depression
Ranjkesh et al, 200521 1 RUL 22.2 8 12 34.1 Depression
Schulze-Rauschenbach et al, 200522 a RUL 28.3 9.9 14 46.7 Depression
anot stated; the ECT device can be set from 0.5 to 1.5 msec at 900 milliamperes.
BF: bifrontal; ECT: electroconvulsive therapy; LART: left anterior right temporal; MMSE: Mini-Mental State Exam; RUL: right unilateral.

  CONCLUSIONS

A course of 6 bitemporal ECT sessions with stimuli of 0.5-msec pulse width and 900-mA current does not commonly produce substantial deficits in basic cognitive function. Because 0.5 msec pulse width also generally is the most efficient and reliably effective pulse width, it seems to be the optimum ECT pulse width or close to it. In comparison, ultra-brief stimuli of 0.3-msec pulse width have shown low and unreliable efficacy in reported studies. For a course of 6 ECT sessions, other electrode placements generally will not have substantially less cognitive side effects than bitemporal ECT with 0.5-msec pulse width stimuli, and the efficacy advantages of bitemporal ECT point to its desirability. For courses of ECT >6 treatments or for patients with a history of unusual cognitive side effects from ECT, electrode placement other than bitemporal (eg, LART) with 0.5-msec pulse width and the new propofol interruption method may have advantages in regard to cognition.7

ACKNOWLEDGEMENT: This article mentions the following medication use that is not approved by the FDA for marketing: propofol for terminating ECT seizure.

DISCLOSURES: Dr. Swartz has received honoraria from the Nordic Association for Convulsive Therapy; royalties from Cambridge University Press; and has equity interests in Somatics, LLC. Drs. Warnell and Thomson report no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.

    REFERENCES

  1. Weiner RD, Rogers HJ, Davidson JR, et al. Effects of stimulus parameters on cognitive side effects. Ann NY Acad Sci. 1986;462:315–325.
  2. Swartz CM. Electricity and electroconvulsive therapy. In: Swartz CM ed. Electroconvulsive therapy and neuromodulation therapies. New York, NY: Cambridge University Press; 2009:3–16.
  3. Swartz CM. Stimulus electrode placement. In: Swartz CM ed. Electroconvulsive therapy and neuromodulation therapies. New York, NY: Cambridge University Press; 2009:430–446.
  4. Kellner CH, Knapp R, Husain MM, et al. Bifrontal, bitemporal and right unilateral electrode placement in ECT: randomised trial. Br J Psychiatry. 2010;196:226–234.
  5. Crum RM, Anthony JC, Bassett SS, et al. Population-based norms for the Mini-Mental State Examination by age and educational level. JAMA. 1993;269:2386–2391.
  6. Bailine SH, Rifkin A, Kayne E, et al. Comparison of bifrontal and bitemporal ECT for major depression. Am J Psychiatry. 2000;15:121–123.
  7. Warnell RL, Swartz CM, Thomson A. Propofol interruption of ECT seizure to reduce side effects: a pilot study. Psychiatry Res. 2010;175:184–185.
  8. Swartz CM, Manly DT. Efficiency of the stimulus characteristics of ECT. Am J Psychiatry. 2000;157:1504–1506.
  9. Hamilton M. A rating scale for depression. J Neurol Neurosurg Psychiatry. 1960;23:56–62.
  10. Bauer J, Hageman I, Dam H, et al. Comparison of propofol and thiopental as anesthetic agents for electroconvulsive therapy. J ECT. 2009;25:85–90.
  11. Barekatain M, Jahangard L, Haghighi M, et al. Bifrontal versus bitemporal electroconvulsive therapy in severe manic patients. J ECT. 2008;24:199–202.
  12. Sackeim HA, Prudic J, Devanand DP, et al. A prospective, randomized, double-blind comparison of bilateral and right unilateral electroconvulsive therapy at different stimulus intensities. Arch Gen Psychiatry. 2000;57:425–434.
  13. Stoppe A, Louza M, Rosa M, et al. Fixed high-dose electroconvulsive therapy in the elderly with depression. J ECT. 2006;22:92–99.
  14. Zervas IM, Calev A, Jandorf L, et al. Age-dependent effects of electroconvulsive therapy on memory. Convuls Ther. 1993;9:39–42.
  15. Zink M, Sartorius A, Lederbogen F, et al. Electroconvulsive therapy in a patient receiving rivastigmine. J ECT. 2002;18:162–164.
  16. Swartz CM. Physiological response to ECT stimulus dose. Psychiatry Res. 2000;97:229–235.
  17. Loo C, Sheehan P, Pigot M, et al. A report on mood and cognitive outcomes with right unilateral ultra-brief pulse width (0.3 ms) ECT and retrospective comparison with standard pulse width right unilateral ECT. J Affect Disord. 2007;103:277–281.
  18. Sackeim HA, Prudic J, Nobler MS, et al. Effects of pulse width and electrode placement on the efficacy and cognitive effects of electroconvulsive therapy. Brain Stimulat. 2008;1:71–83.
  19. McCormick LM, Brumm MC, Benede AK, et al. Relative ineffectiveness of ultra-brief right unilateral versus bilateral electroconvulsive therapy in depression. J ECT. 2009;25:238–242.
  20. Swartz CM. Asymmetric bilateral right frontotemporal left frontal stimulus electrode placement for electroconvulsive therapy. Neuropsychobiology. 1994;29:174–178.
  21. Ranjkesh F, Barekatain M, Akuchakian S. Bifrontal versus right unilateral and bitemporal electroconvulsive therapy in major depressive disorder. J ECT. 2005; 21:207–210.
  22. Schulze-Rauschenbach SC, Harms U, Schlaepfer TE, et al. Distinctive neurocognitive effects of repetitive transcranial magnetic stimulation and electroconvulsive therapy in major depression. Br J Psychiatry. 2005;186:410–416.

CORRESPONDENCE: Ronald L. Warnell, MD, Department of Psychiatry, Loma Linda University, 1686 Barton Road, Redlands, CA 92373 USA, E-MAIL: rwarnell@llu.edu