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QUESTION: In patients with major depressive disorder (MDD), how do different dosages of right unilateral (RUL) electroconvulsive therapy (ECT) compare with high dosage bilateral (BL) ECT for antidepressant response and cognitive side effects?
New York State Psychiatric Institute, New York, USA.
84 patients (96% inpatients) who had MDD with a score of ≥18 on the 24 item Hamilton Rating Scale for Depression (HRSD). Exclusion criteria were history of functional psychosis or rapid cycling bipolar illness; neurological abnormality; substance abuse in the past year; ECT in the past 6 months; or severe medical illness. 80 patients (mean age 57 y, 64% women) completed the study.
At the first ECT session patients' seizure threshold (ST) was quantified and they were allocated to 1 of 4 groups with 20 patients each: RUL ECT with stimulus intensity at either 1.5 (low dose), 2.5 (moderate dose), or 5.0 (high dose); or BL ECT at 2.5 (high dose) times the initial ST.
Main outcome measures
Initial antidepressant response (decrease of ≥60% in HRSD scores and a score of ≤16 at 1 to 2 d after the last treatment). Final responders maintained response 1 week after the final treatment. Cognitive side effects were evaluated using anterograde and retrograde memory tests.
High dose RUL and BL ECT initial and final responder rates did not differ. Compared with BL ECT, fewer RUL ECT low and moderate dosage group patients had initial response (p=0.002) (table). Fewer RUL ECT group patients had final response than did BL ECT group patients (p=0.03) (table). Cognitive disturbance was greatest in the BL ECT group. The rates for disorientation immediately after treatment lasting >90 minutes and the extent of word recall or recognition were greatest with BL ECT than with any RUL ECT dosage (p=0.002 and p=0.03, respectively, for difference between BL ECT and all RUL ECT groups). 2–7 days after final treatment BL ECT resulted in greater impairment than any RUL ECT dosage on several cognitive measures. Cognitive differences persisted 2 months after completion of ECT.
In patients with major depression, markedly suprathreshold right unilateral electroconvulsive therapy (ECT) was as efficacious as high dose bilateral ECT for antidepressant response and had fewer cognitive side effects.
The studies by Sackeim et al and McCall et al address the continuing controversy about the benefits and risks of UL ECT and BL ECT. The report by Sackeim et al is the third since 1987 by these authors seeking to increase the efficacy of UL ECT and to sustain its immediate lesser cognitive effects compared with bilateral placement (BL ECT). RUL ECT with dosages 5 times ST is reported to be equal in efficacy to BL ECT at 2.5 times ST, and with fewer short term cognitive side effects. The sample size (20 patients per group), however, is too small to ensure that clinically important differences do not exist. Cognition was assessed immediately after seizure and 2–7 days after the last treatment, and favoured RUL ECT over BL ECT. For most patients, however, the immediate cognitive effects diminish after 2 months and this benefit may not be sufficient to justify RUL ECT given the uncertainties about its efficacy compared with BL ECT.
The stimulus dosing of BL ECT was applied at 2.5 times ST in the study by Sackeim et al, but BL ECT has been shown to be effective at 1.5 times ST in a previous study by these authors.1 The selection of a higher BL ECT dosing intensity ensured efficacy, but also greater cognitive side effects; RUL ECT at a high dosage stimulus may confer a cognitive advantage in this regard. Clinical application of these results is problematic because the BL ECT dosage in this study markedly exceeds that used in most treatment settings.
Even if efficacy is equivalent, and cognitive side effects are lessened, such high dosing will be impractical for many clinicians. For example, the US Food and Drug Administration regulations on ECT output would not permit the highest RUL ECT intensities used in this study for about 20% of patients.
McCall et al compared titrated moderately suprathreshold with fixed high dose RUL ECT. Previously published trials have reported RUL ECT efficacy and memory effects to be sensitive to stimulus dosing above ST.1 McCall et al confirmed these findings in their study as retrospective analysis of the fixed high dose RUL ECT group showed that treatments at dosage intensities from 3.15 to 5.04 times ST were much less effective than those at intensities from 8.4 to 12.6 times ST. Differences detected in adverse effects were apparent 1–2 days after the ECT course at a dosage of 3.15 to 5.04 times ST, but were dramatically worsened at a dosage of 8.4 to 12.6 times ST. Such worsening effects on immediate memory paralleled improvement in antidepressant efficacy. As with the results of the study by Sackeim et al, clinicians will have to balance the antidepressant benefit of high dose RUL ECT against increased memory impairment.
The BL v RUL ECT controversy remains unresolved. Readers should be cautious about adopting a recommendation for RUL ECT at 6 times ST in their clinical practice, even for depressed patients. Short term cognitive side effects are less likely, but problems with small sample size and choice of BL ECT dosage intensity in the study by Sackeim et al mean that important clinical questions remain about their comparative efficacy. The results from McCall et al suggest that, as assessed, RUL ECT is too inefficient for routine use and the reduced memory impairment is of limited clinical significance. My recommendation for practitioners is that BL ECT at 1.5 times the estimated or measured ST remains the clinical standard.
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