ONSET AND TIME-COURSE OF ANTIDEPRESSANT ACTION - PSYCHOPHARMACOLOGICAL IMPLICATIONS OF A CONTROLLED TRIAL OF ELECTROCONVULSIVE-THERAPY

Onset and time course of antidepressant effect were examined in 47 pat ients with major depressive disorder who had been randomly assigned to twice weekly bilateral, brief pulse electroconvulsive therapy plus on e simulated treatment per week (ECTx2) or to a three times weekly sche dule of administration (ECTx3). Rapid improvement was observed in the ECTx3 group in whom the number of real ECTs to 30% reduction on the Ha milton Depression Scale (HAM-D) was 3.2 +/- 1.90, administered over 7. 3 +/- 4.43 days and to 60% reduction, 5.9 +/- 3.09 real ECTs over 13.7 +/- 7.21 days. Among the responders in both groups combined, 24.3 +/- 29.58% of the overall improvement in HAM-D was contributed by the fir st real ECT, 60.9 +/- 28.13% by the first four real ECTs and 91.6 +/- 25.82% by the first eight. Although 85.3% of the responders had reache d 60% HAM-D improvement after eight ECTs, a clinically significant min ority (14.7%) responded later in the course (ECT 9-12). However, respo nse was predictable on the basis of symptomatic improvement (30% on th e HAM-D) by the sixth real ECT. Thirty-three out of 34 responders woul d have been correctly identified by this criterion and only 2 out of 1 3 non-responders mis-identified (P<0.000001). Once achieved, the antid epressant effect was stable without continuation pharmacotherapy, unti l 1 week after the last treatment and on lithium carbonate (Li) or Li plus clomipramine for a further 3 weeks. These findings confirm the cl inical impression that ECT is a rapidly effective treatment for major depression with a shorter latency than generally reported for antidepr essant drugs. Elucidation of its neurobiological mechanisms could cont ribute to the development of pharmacological agents with a similar pro file.