Section Review Central & Peripheral Nervous Systems: New antidepressant agents: Recent pharmacological developments leading to improved efficacy

Abstract

The disadvantages of the standard tricyclic antidepressants (TCAs) and monoamine oxidase inhibitors (MAOIs), in terms of side-effects and fatal overdose, led to the development and release of seven new antidepressants in the USA in the past eight years with approximately another ten in various stages of development. This paper will focus on how recent advances in biochemistry and kinetics have led to improved efficacy. In particular, the more specific 5-HT agents appear effective for ‘typical’ depression and pain; the less specific ones for depression associated with obsessive-compulsive disorder. The selective serotonin reuptake inhibitors (SSRIs) are particularly suited for treatment of depression associated with diabetes mellitus; the serotonin and norepinephrine reuptake inhibitor (SNRI), venla-faxine, for resistant depression; and bupropion, for atypical depression. The serotonin receptor modulator (SRM), nefazodone, in contrast, is particularly suited for the treatment of depression associated with insomnia because of its combined SSRI and post-synaptic 5-HT_2A/C receptor antagonist effects. In terms of kinetics, important factors include, particularly: elimination half-lives, linearity of kinetics, therapeutic blood levels, effects on hepatic microen-zymes, and effects on memory and alertness. Discussion of these seven antidepressants is followed by a brief review of knowledge concerming other potential antidepressants in development.