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 single action of serotonin reuptake inhibition can improve several psychiatric conditions. In order to understand this apparent paradox it is necessary...

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Bibliographic Details
Published in:European neuropsychopharmacology 1999-07, Vol.9, p.S81-S86
Main Authors: Nutt, David J., Forshall, Sam, Bell, Caroline, Rich, Ann, Sandford, John, Nash, Jon, Argyropoulos, Spilios
Format: Article
Language:English
Subjects:
Anxiety disorders
Anxiety Disorders - drug therapy
Brain - drug effects
Brain - physiopathology
Depression
Depressive Disorder - drug therapy
Humans
Pharmacokinetics
Selective serotonin reuptake inhibitors
Serotonergic receptors
Serotonin - metabolism
Serotonin Uptake Inhibitors - therapeutic use
Space life sciences
Synapses - drug effects
Synapses - physiology
Tryptophan depletion
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Summary:Selective serotonin reuptake inhibitors (SSRIs) have demonstrated efficacy in depression and anxiety disorders. This raises the question of how the single action of serotonin reuptake inhibition can improve several psychiatric 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 research into depression and has shown that, in patients receiving an SSRI whose depression is in remission, depleting serotonin leads to recurrence of the disorder. Similar results have been found for panic disorder. This suggests that increased levels of serotonin are necessary in the synapse for the SSRI to be effective in the treatment of depression and panic disorder. In obsessive compulsive disorder, depletion of serotonin in patients recovered on an SSRI does not cause relapse; receptor adaptation may be more important. Variations within the SSRI drug class, such as the selectivity ratios for serotonin versus noradrenaline uptake, elimination half-life, and affinity for the 5-HT 2 receptor have been identified and may be important determinants of efficacy, side effects and clinical use.
ISSN:0924-977X
1873-7862
DOI:10.1016/S0924-977X(99)00030-9