Development of new treatments for depression

The mixed actions of the older tricyclic antidepressants make them generally unsuitable as pharmacologic tools in investigating mechanisms of antidepressant effect. Tricyclics are also relatively dangerous in overdose, and their patient acceptability is limited by marked side effects and cardiotoxicity. The current trend in the development of new antidepressants is to identify pharmacologically active molecules that have selective action. Compounds with a selective effect in blocking serotonin reuptake have recently been developed. Among these, fluoxetine is of substantial theoretical interest because, unlike other serotonin uptake inhibitors, it is rather specific and does not appear to down-regulate beta-receptors. Assessment of the relative efficacy of such compounds should provide insight into the mechanisms of antidepressant effect. Prerequisites of clinical trials for new antidepressants are briefly reviewed.