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Short-term Efficacy and Adverse Effects

Harold A. Sackeim, PhD; Elaine M. Dillingham, BA; Joan Prudic, MD; Thomas Cooper, MA; W. Vaughn McCall, MD; Peter Rosenquist, MD; Keith Isenberg, MD; Keith Garcia, MD; Benoit H. Mulsant, MD; Roger F. Haskett, MD

Arch Gen Psychiatry. 2009;66(7):729-737.

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, 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.

Author Affiliations: Departments of Biological Psychiatry (Drs Prudic and Sackeim and Ms Dillingham) and Analytical Psychopharmacology (Mr Cooper), New York State Psychiatric Institute, New York; Departments of Psychiatry (Drs Prudic and Sackeim, Ms Dillingham, and Mr Cooper) and Radiology (Dr Sackeim), Columbia University, New York; Department of Psychiatry and Behavioral Medicine, Wake Forest University Health Sciences, Winston-Salem, North Carolina (Drs McCall and Rosenquist); Department of Psychiatry, Washington University School of Medicine, St Louis, Missouri (Drs Isenberg and Garcia); Western Psychiatric Institute and Clinic and Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania (Drs Mulsant and Haskett); and Department of Psychiatry, University of Toronto and Centre for Addiction and Mental Health, Toronto, Ontario, Canada (Dr Mulsant)

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