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QUESTION: In patients with a major depressive disorder (MDD), how do titrated moderately suprathreshold and fixed high dose right unilateral (RUL) electroconvulsive therapy (ECT) compare for acute antidepressant response and cognitive side effects?
Tertiary care centre in Winston-Salem, North Carolina, USA.
72 patients (90% outpatients) who were ≥18 years of age (mean age 64 y, 75% women) and met DSM-III-R criteria for MDD. Exclusion criteria were a history of functional psychosis, active substance abuse, mental retardation or neurological illness, ECT in the past 4 months, score of <18 on the Mini-Mental State Examination (MMSE), score of <20 on the Hamilton Rating Scale for Depression (HRSD), need for bilateral ECT because of extreme severity of illness, refusal to cooperate with testing, or predominantly left handedness. Follow up was complete for antidepressant response and 88% for cognitive side effects.
RUL ECT seizure threshold (ST) was determined at the first session. Patients were then allocated to titrated RUL ECT at 2.25 times the initial ST (mean dose 136 millicoulombs [mC]) (n=36) or a fixed high dose of 403 mC of RUL ECT (n=36). The attending physician determined the number of treatments.
Main outcome measures
Antidepressant response (decrease of ≥60% in HRSD score and a final score of ≤12), and global cognitive disturbance (decrease of ≥5 points on the MMSE) 1–2 days after the course of ECT, and retrograde and anterograde memory function.
Analysis of the antidepressant response was by intention to treat. The rate of antidepressant response was greater in the fixed high dose RUL ECT group than in the titrated group (p=0.02), but the high dose group had more cognitive disturbance (p=0.02) (table⇓). Autobiographical memory was greater in the titrated RUL ECT group than in the fixed high dose group (percentage of autobiographical recall 66.1% v 53.5%, p=0.01).
In patients with a major depressive episode, titrated moderately suprathreshold right unilateral (RUL) electroconvulsive therapy (ECT) produced a lower antidepressant response rate, but fewer cognitive side effects than fixed high dose RUL ECT.
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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