Calcium signaling cascades, antidepressants and major depressive disorders

Abstract

The discovery of effective antidepressants among the monoamine oxidase inhibitors and tricyclic compounds inhibiting monoamine uptake stimulated and drove research on the actions of antidepressants and the pathophysiology of major depression for nearly two decades (Stone, 1983). Newly discovered compounds with selectivity to antagonize the reuptake of serotonin have driven this research in recent years (Caldecott-Hazard et al., 1991; Charney, 1998; Maj et al., 1984). However, the response rate with any given antidepressant treatment has remained essentially unchanged since the early 1960’s. Regardless of whether patients are prescribed monoamine oxidase inhibitors, tricyclic compounds or serotonin reuptake inhibitors, response rates hover between 60-65%. Moreover, in all cases, 3-6 weeks of drug administration is required to produce a therapeutic response, suggesting the agency of factors other than or in addition to the acute effects of these drugs (Charney, 1998; Oswald et al., 1972). Given the difficulties in maintaining patients in treatment after unsuccessful drug trials and the risk of self-injurious behavior and suicide until remission of depressive symptoms, the need for rapidly acting antidepressants with high response rates remains as pressing now as it was 40 years ago.