Mechanisms of action of selective serotonin reuptake inhibitors in the treatment of psychiatric disorders

Selective serotonin reuptake inhibitors (SSRIs) have demonstrated efficacy in depression and anxiety disorders. This raises the question of how the si ngle action of serotonin reuptake inhibition can improve several psychiatri c conditions. In order to understand this apparent paradox it is necessary to consider where SSRIs act in the pathogenic process underlying depression or anxiety disorders. Tryptophan depletion has been used extensively in re search into depression and has shown that, in patients receiving an SSRI wh ose depression is in remission, depleting serotonin leads to recurrence of the disorder. Similar results have been found for panic disorder. This sugg ests that increased levels of serotonin are necessary in the synapse for th e SSRI to be effective in the treatment of depression and panic disorder. I n obsessive compulsive disorder, depletion of serotonin in patients recover ed on an SSRI does not cause relapse; receptor adaptation may be more impor tant. Variations within the SSRI drug class, such as the selectivity ratios for serotonin versus noradrenaline uptake, elimination half-life, and affi nity for the 5-HT2 receptor have been identified and may be important deter minants of efficacy, side effects and clinical use. (C) 1999 Elsevier Scien ce B.V. All rights reserved.