SEROTONIN SELECTIVE ANTIDEPRESSANT DRUGS - PAST, PRESENT, FUTURE

Classic antidepressant drugs, amine uptake inhibitors of the imipramine type and the monoamine oxidase inhibitors, alter the functioning of serotonin (5-hydroxytryptamine, 5-HT) neurons in the brain. This discovery, made more than two decades ago, has had a profound impact on the study of depressive illness as well as on the development of new models of antidepressant treatment. Apart from their obvious clinical value, antidepressant drugs have come to be used as research tools to study the pathophysiology of depressive illness. A main goal in the development of antidepressant drugs has been to design drugs with more selective effects on the nerve cells that are thought to be important in depressive illness, thereby avoiding unnecessary side effects and possibly enhancing therapeutic effects. Drugs that selectively affect 5-HT neurons have proved to be uptake inhibitors-including fluoxetine, fluvoxamine, paroxetine, sertraline, and citalopram-and are now available. All of them appear to have an antidepressant effect equivalent to standard reference compounds, with a different spectrum of side effects. One of the most interesting aspects of the serotonergic drugs is their broad spectrum of action, in particular, their effects in patients with obsessive-compulsive disorder, panic disorder, and possibly some disorders of impulse control. There is still relatively little knowledge of which aspects of 5-HT function are important for the antidepressant, antiobsessive, and antipanic effects. The availability of drugs that selectively affect the different 5-HT receptors, such as the partial 5-HT1A agonist gepirone, will presumably be helpful for modern studies of the ''anatomy of melancholy.''