Selective serotonin reuptake inhibitors in affective disorders — I. Basic pharmacology

Goodnick, Paul J.; Goldstein, Burton J.

doi:10.1177/0269881198012003021

Cited by 183Treatment of Major DepressionNeurotransmitter Receptor Influence on BehaviorPharmacogenetics and Drug Metabolism

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Selective serotonin reuptake inhibitors in affective disorders — I. Basic pharmacology

Goodnick, Paul J., Goldstein, Burton J.·1998·Journal of Psychopharmacology

DOI 10.1177/0269881198012003021

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Abstract

The selective serotonin reuptake inhibitors (SSRIs), citalopram, fluoxetine, fluvoxamine, paroxetine and sertraline, are the result of rational research to find drugs that were as effective as the tricyclic antidepressants but with fewer safety and tolerability problems. The SSRIs selectively and powerfully inhibit serotonin reuptake and result in a potentiation of serotonergic neurotransmission. The property of potent serotonin reuptake appears to give a broad spectrum of therapeutic activity in depression, anxiety, obsessional and impulse control disorders. However, despite the sharing of the same principal mechanism of action, SSRIs are structurally diverse with clear variations in their pharmacodynamic and pharmacokinetic profiles. The potency for serotonin reuptake inhibition varies amongst this group, as does the selectivity for serotonin relative to noradrenaline and dopamine reuptake inhibition. The relative potency of sertraline for dopamine reuptake inhibition differentiates it pharmacologically from other SSRIs. Affinity for neuroreceptors, such as sigma1, muscarinic and 5-HT 2c, also differs widely. Furthermore, the inhibition of nitric oxide synthetase by paroxetine, and possibly other SSRIs, may have significant pharmacodynamic effects. Citalopram and fluoxetine are racemic mixtures of different chiral forms that possess varying pharmacokinetic and pharmacological profiles. Fluoxetine has a long acting and pharmacologically active metabolite. There are important clinical differences among the SSRIs in their pharmacokinetic characteristics. These include differences in their half-lives, linear versus non-linear pharmacokinetics, effect of age on their clearance and their potential to inhibit drug metabolising cytochrome P450 (CYP) isoenzymes. These pharmacological and pharmacokinetic differences underly the increasingly apparent important clinical differences amongst the SSRIs.

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All SSRIs except paroxetine are devoid of anticholinergic properties.
“Goodnick and Goldstein (19) suggested that all SSRIs except paroxetine are devoid of anticholinergic properties.”
From Risk of Dementia Among Elderly Nursing Home Patients Using Paroxetine and Other Selective Serotonin Reuptake Inhibitors (2015) · cites this paper as [19]
SSRIs vary in their pharmacodynamic and pharmacokinetic profiles, despite having the same principal mechanism of action.
“SSRIs vary in their pharmacodynamic and pharmacokinetic profiles, despite having the same principal mechanism of action (19).”
From Risk of Dementia Among Elderly Nursing Home Patients Using Paroxetine and Other Selective Serotonin Reuptake Inhibitors (2015) · cites this paper as [19]

Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor
Palmer, R. M. J., Ferrige, A. G., & Moncada, S. (1987) · Nature · doi:10.1038/327524a0 · Cited by 10,704
Fluoxetine, paroxetine, sertraline, and fluvoxamine in a prospective, multicenter, and descriptive clinical study of 344 patients
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Serotonin Reuptake Inhibitor Withdrawal
Coupland, N. J., Bell, C. J., & Potokar, J. P. (1996) · Journal of Clinical Psychopharmacology · doi:10.1097/00004714-199610000-00003 · Cited by 303
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Authors: Goodnick, P. J., & Goldstein, B. J.
Affiliations: University of Miami (US)
Venue: Journal of Psychopharmacology
Publisher: SAGE Publications
Published: 1998-07
Volume: 12
Issue: 4_suppl
Pages: 5-S20
ISSN: 0269-8811 (ISSN-L)
1461-7285
DOI: 10.1177/0269881198012003021
OpenAlex: W1881287185
Cited by: 183
References: 5
Citations by year: 2026: 8 · 2025: 5 · 2024: 6 · 2023: 2 · 2022: 4 · 2021: 4 · 2020: 4 · 2019: 6 · 2018: 3 · 2017: 4 · 2016: 8 · 2015: 5 · 2014: 7 · 2013: 4 · 2012: 9
FWCI: 0.65
Type: journal article
Language: en
Open access: closed
Licence: journals.sagepub.com/page/policies/text-and-data-mining-license (tdm)
Locations: Journal of Psychopharmacology (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Pharmacology (medical) › Treatment of Major Depression
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
Keywords: selective serotonin reuptake inhibitors, serotonin reuptake inhibition, citalopram, fluoxetine, fluvoxamine, paroxetine, sertraline, depression, anxiety disorders, obsessive-compulsive disorder, impulse control disorders, pharmacodynamics, pharmacokinetics, dopamine uptake inhibition, chiral enantiomers, cytochrome P450 inhibition, drug interactions, receptor binding affinity
MeSH terms: Humans, Selective Serotonin Reuptake Inhibitors, Antidepressive Agents, Second-Generation, Mood Disorders

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