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

Paul J. Goodnick, Burton J. Goldstein

Research output: Contribution to journalReview articlepeer-review

161 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)S5-S20
JournalJournal of Psychopharmacology
Issue number3 SUPPL. B
StatePublished - Jan 1 1998


  • 5-HT(2c)
  • Anticholinergic
  • Cytochrome P450
  • Dopamine
  • Nitric oxide synthetase
  • Potency
  • Selectivity
  • Sigma1

ASJC Scopus subject areas

  • Pharmacology
  • Psychiatry and Mental health
  • Neuroscience(all)
  • Pharmacology (medical)


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