Although electroconvulsive therapy (ECT) is a highly effective and widely used treatment for severe depression, an optimum schedule of administration has never been definitively established. Available evidence strongly suggests that twice weekly treatments are effective; yet more frequent schedules involving a greater number of ECT's, continue to be used in many centers, particularly in the U.S.A. Severity of ECT-induced memory impairment has been shown to be cumulatively related to frequency and number of treatments. The reduction in both parameters which a twice weekly schedule permits, is therefore highly desirable provided that therapeutic benefit can be definitively shown to be unimpaired. The present protocol therefore calls for a random assignment, double-blind comparison, controlled by the use of simulated ECT between twice and three times weekly schedules of ECT administration. Clinical response and cognitive function will be serially rated during the 4 week acute treatment period and long-term effects during 6 month continuation therapy with lithium carbonate. The underlying hypothesis of this proposal is that the antidepressant action of ECT is time dependent, and is not accelerated by increasing the frequency of treatment administration beyond an optimum level. Biological effects relevant to antidepressant mechanisms should be induced by the least frequent schedule which is clinically effective. Two potentially important parameters will be studied in this context: (1) Preclinical studies have strongly implicated central serotonergic effects in the mechanism of action of antidepressant treatments including ECT. In the present protocol, the plasma prolactin response to fenfluramine will be used as a marker for changes in central serotonergic function induced by ECT. (2) A recent neurophysiological theory suggests that the induction, by ECT, of a central hypometabolic state, may underlie its antidepressant action. in the present protocol, seizure threshold increases which putatively reflect the ECT-induced neural hypometabolic state, will be serially monitored during the treatment course. The effects of twice and three times weekly ECT on both these parameters will be compared and correlated with treatment outome. The findings of this project are therefore likely to have important implications for the mechanism of action of ECT in addition to their potential impact on clinical practice.

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National Institute of Mental Health (NIMH)
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Herzog Hospital-Ezrath Nashim
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Shapira, B; Tubi, N; Lerer, B (2000) Balancing speed of response to ECT in major depression and adverse cognitive effects: role of treatment schedule. J ECT 16:97-109
Lerer, B; Gillon, D; Lichtenberg, P et al. (1996) Interrelationship of age, depression, and central serotonergic function: evidence from fenfluramine challenge studies. Int Psychogeriatr 8:83-102
Shapira, B; Lidsky, D; Gorfine, M et al. (1996) Electroconvulsive therapy and resistant depression: clinical implications of seizure threshold. J Clin Psychiatry 57:32-8
Shapira, B; Gorfine, M; Lerer, B (1995) A prospective study of lithium continuation therapy in depressed patients who have responded to electroconvulsive therapy. Convuls Ther 11:80-5
Lerer, B; Shapira, B; Calev, A et al. (1995) Antidepressant and cognitive effects of twice- versus three-times-weekly ECT. Am J Psychiatry 152:564-70
Segman, R H; Shapira, B; Gorfine, M et al. (1995) Onset and time course of antidepressant action: psychopharmacological implications of a controlled trial of electroconvulsive therapy. Psychopharmacology (Berl) 119:440-8
Shapira, B; Newman, M; Lerer, B (1994) Serotonergic mechanisms in depression: clinical insights and biological correlates. Isr J Med Sci 30:162-7
Shapira, B; Cohen, J; Newman, M E et al. (1993) Prolactin response to fenfluramine and placebo challenge following maintenance pharmacotherapy withdrawal in remitted depressed patients. Biol Psychiatry 33:531-5
Lichtenberg, P; Shapira, B; Blacker, M et al. (1992) Effect of fenfluramine on mood: a double-blind placebo-controlled trial. Biol Psychiatry 31:351-6
Shapira, B; Lerer, B; Kindler, S et al. (1992) Enhanced serotonergic responsivity following electroconvulsive therapy in patients with major depression. Br J Psychiatry 160:223-9

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