Central issues regarding the mechanisms of action of electroconvulsive therapy: directions for future research.

Over 100 theories have been offered to account for the therapeutic effects of electroconvulsive therapy (ECT). The findings that technical factors in treatment administration strongly determine the magnitude of antidepressant effects contradict a number of psychological explanations that focus on placebo effects and patient expectations. The independence of therapeutic and adverse cognitive side effects implies an independence of mechanisms. Biological investigation of mechanisms has been impeded by the belief that therapeutic effects are an intrinsic outcome of seizure elicitation. However, recent research has contradicted long-held conceptions of the necessary and sufficient conditions for ECT's antidepressant effects. The recognition that generalized seizures that lack therapeutic properties can be reliably elicited provides new opportunities for examining the neurophysiological and biochemical determinants of efficacy. Neurophysiological and biochemical theories are described and future research directions are outlined.