Mechanisms of action of selective serotonin reuptake inhibitors in the treatment of psychiatric disorders
by
Nutt DJ, Forshall S, Bell C, Rich A,
Sandford J, Nash J, Argyropoulos S
University of Bristol,
Psychopharmacology Unit,
School of Medical Sciences,
University Walk, UK.
Eur Neuropsychopharmacol 1999 Jul; 9 Suppl 3:S81-6

ABSTRACT

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-HT2 receptor have been identified and may be important determinants of efficacy, side effects and clinical use.

TCAs
SSRIs
5-HT2
Serotonin
Sertraline
Fluoxetine
Citalopram
Paroxetine
Fluvoxamine
SSRIs: review
Drugs and sex
SSRIs compared
SSRI suicide link?
SSRIs: interactions
Serotonin control genes
Antidepressant mechanisms
SSRIs and emotional blunting
SSRIs and depressed children
Where are we going with SSRIs?
SSRIs and cognitive performance
Are SSRI antidepressants little better than placebos?

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