Effect of concomitant pharmacotherapy on electroconvulsive therapy outcomes: Short-term efficacy and adverse effects

Context: Medication resistance is the leading indication for use of electroconvulsive therapy (ECT) in major depression. The practice of stopping antidepressant medications prior to ECT derived from studies in the 1960s and 1970s in nonresistant samples. There is also continuing controversy regarding the relative efficacy and adverse effects of right unilateral and bilateral ECT. Objective: To test the hypotheses that, compared with placebo, concomitant treatment with nortriptline or venlafaxine during the ECT course enhances short-term efficacy without a meaningful effect on adverse effects and reduces the rate of post-ECT relapse, and to test the hypotheses that high-dose, right-sided, unilateral ECT is equivalent in efficacy to moderate-dosage bilateral ECT and retains advantages with respect to cognitive adverse effects. Design: Prospective, randomized, triple-masked, placebo-controlled study conducted from 2001 through 2005. Setting: Three university-based hospitals. Patients: Of approximately 750 consecutive patients referred for ECT, 319 with a major depressive episode consented, consented, were randomized to pharmacological or ECT treatment conditions, and received at least 1 ECT treatment. Main Outcome Measures: Scores on the Hamilton Rating Scale for Depression, remission rate following completion of ECT, and selective measures of cognitive adverse effects. Results: Treatment with nortriptyline enhanced the efficacy and reduced the cognitive adverse effects of ECT relative to placebo. Venlafaxine resulted in a weaker degree of improvement and tended to worsen cognitive adverse effects. High-dosage right unilateral ECT did not differ or was superior to bilateral ECT in efficacy and resulted in less severe amnesia. Conclusions: The efficacy of ECT is substantially increased by the addition of an antidepressant medication, but such medications may differ in whether they reduce or increase cognitive adverse effects. High-dose, right-sided, unilateral ECT is at least equivalent to moderate-dosage bilateral ECT in efficacy, but retains advantages with respect to cognitive adverse effects.