Chapter category: Neuropharmacology
The Mechanism of Action of SSRIs:A New Hypothesis
Selective Serotonin Reuptake Inhibitors (SSRIs): Past Present and Future
Edited by: S. Clare StanfordISBN: 1-57059-649-2
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Chapter authors:
Lori L. Davis, Kimberly A. Yonkers, Madhukar Trivedi, Gerald L.Kramer and Frederick Petty
The introduction of the selective serotonin reuptake inhibitors (SSRIs) into medical treatment in the 1980s revolutionized psychiatric practice and fueled the interest in the role of serotonin (5-hydroxytryptamine, 5-HT) in the underlying neurobiology of the psychiatric disorders. In reviewing the literature, one is struck by a curious and interesting dichotomy between the fairly selective effect that these drugs have on the serotonergic system and the remarkably `non-selective' manner in which they are used clinically. In actuality, these compounds vary considerably regarding their relative `selectivity' for 5-HT reuptake, and some SSRIs have significant action on other biogenic amine neurotransmitter systems (for further details: see Chapter 10). However, there is no doubt that the SSRIs are a marked and significant improvement on our previous attempts to selectively increase 5-HT neurotransmitter function with precursors such as tryptophan. Certainly, the SSRIs are far more selective, as a class, than the previously available tricyclic antidepressants (TCAs).
The SSRI's remarkably broad spectrum of utility, crossing (and blurring) diagnostic boundaries of depressive disorders, panic disorder, obsessive-compulsive disorder, bulimia, post-traumatic stress disorder, premenstrual dysphoric disorder and, no doubt, other conditions, raises important and potentially controversial questions regarding the utility, if not outright validity, of contemporary diagnostic terminology, presently codified in DSM-IV. In some respects, this promotes a degree of diagnostic nihilism, similar to the scenario in American psychiatry in the pre-psychopharmacologic era, when psychoanalysis was widely regarded as an effective treatment of choice for most, if not all, neurotic patients, regardless of precise diagnosis. In other words, if the treatment works, independent of diagnosis, why bother to diagnose at all? A new diagnostic scheme may evolve from clinical experience and further neurobiological research, in which we might diagnose `serotonin (5-HT) deficit disorder,' rather than the clinically descriptive, criterion-driven diagnostic schemes in vogue today. Thus, from both clinical and theoretical perspectives, the SSRIs have, and will continue to, revolutionize psychiatry.
Additional chapters from this book:
SSRIs: Where Now, Where Next?
David J. Heal and Sharon C. Cheetham
It is interesting to note that in the title of their review on fluoxetine (`Prozac',Lilly), Wong, Bymaster and Engleman1 describe this drug as "the first selective serotonin...
The Mechanism of Action of SSRIs:A New Hypothesis
Lori L. Davis, Kimberly A. Yonkers, Madhukar Trivedi, Gerald L.Kramer and Frederick Petty
The introduction of the selective serotonin reuptake inhibitors (SSRIs) into medical treatment in the 1980s revolutionized psychiatric practice and fueled the interest in the role of seroto...
SSRI-Induced Changes in Catecholaminergic Transmission
S. Clare Stanford
The selective serotonin reuptake inhibitors (SSRIs) are a chemically diverse group of compounds which share the characteristic of potently inhibiting neuronal reuptake of serotonin (5-hydroxyt...
SSRI-Induced Functional Changes in Serotonergic Neurons
Ildefonso Hervás, Andreu Raurich, Luz Romero, Roser Cortés and Francesc Artigas
The term `SSRIs' encompasses several chemical agents that have in common their ability to inhibit selectively the function of the serotonin (5-hydroxytryptamine, 5-HT) transporter. This is loc...
Mechanism of Action of Different Classes of Antidepressants: Evidence from 5-HT Challenge Studies
Ian M. Anderson and Christopher Mortimore
The discovery in the 1950s that imipramine and iproniazid had antidepressant properties was soon followed by the recognition that they acted on monoamine systems. This laid the foundation f...
SSRIs and Suicide
John A. Henry and Carol A. Rivas
The selective serotonin reuptake inhibitors (SSRIs) have increased in popularity and extent of use since their introduction. At the same time, our knowledge concerning the relationship between...
SSRIs and Sexual Function
Peter A. Sargent and Guy M. Goodwin
Human sexual dysfunction is described in ICD-101 under broad categories, reflecting the pragmatic division of the normal sexual response, into phases of desire, arousal, orgasm and ...
SSRIs, Drug Withdrawal and Abuse: Problem or Treatment?
C. Heather Ashton and Allan H. Young
Selective serotonin reuptake inhibitors (SSRIs) have considerable advantages over earlier antidepressants, such as most tricyclic antidepressants (TCAs) and monoamine oxidase inhibitors (MA...
SSRIs and Patient Groups with Specific Treatment Problems
John Hughes, Brian Lunn and John O'Brien
Selective serotonin reuptake inhibitors (SSRIs), whilst initially launched solely as anti- depressants, have been used increasingly as treatments for other disorders and in patients who are vu...
SSRIs in Depression: Distinctive Actions?
Julie Newman and Andrew A. Nierenberg
The introduction of the selective serotonin reuptake inhibitors (SSRIs) has radically changed the treatment of depression worldwide. The five currently marketed SSRIs, fluoxetine, sertraline, ...
Clinical Pharmacokinetics of SSRIs
Pierre Baumann, Chin B Eap and Pierre Voirol
Citalopram,1 fluoxetine,2,3 fluvoxamine,4 paroxetine5 and sertraline6 are the five anti- depressants which are known as selective seroton...
The Discovery of The SSRIs: A Milestone In Neuropsychopharmacology and Rational Drug Design
Arvid Carlsson
Besides being a major therapeutic advance, the selective serotonin reuptake inhibitors (SSRIs) have become important tools in basic and clinical brain research. They were the first drugs to...
