Antidepressants are associated with a variety of side-effects, ranging in severity from the merely annoying to those with significant morbidity and even potential mortality. Prominent among the latter are cardiovascular effects, which have provided much of the impetus for the development of newer antidepressants such as fluoxetine. In this paper, we will review these cardiovascular effects, but as this has been previously undertaken elsewhere (e.g. Glassman & Bigger, 1981; Marshall & Forker, 1882; Glassman, 1984a), our consideration will be selective, with emphasis on methodological issues of relevance to the evaluation of new antidepressants. Since mechanisms of cardiac side-effects are best understood in relation to tricyclic antidepressants (TCAs), these will be a major focus, and will provide a background for the consideration of newer agents.

While less is known regarding the side-effects of the newer antidepressants, examination of the evolution of knowledge and opinions regarding their safety is particularly pertinent in that it illustrates the waxing and waning of enthusiasm that typically accompanies the introduction of new therapeutic agents. We review below the growing body of data regarding fluoxetine and some of the other serotonin-selective antidepressants, as well as discussing serotonergic effects on the cardiovascular system and their implications for the clinical use of these agents. Since the interactions between antidepressants and drugs used to treat cardiovascular disorders have been reviewed by Risch et al (1982) and Glassman & Salzman (1987), these will not be considered here.