Care of depression in the elderly: comparative pharmacokinetics of SSRIs

Citalopram, fluoxetine, fluvoxamine, paroxetine and sertraline are the selective serotonin reuptake inhibiting antidepressants available. They differ by their chemical structure, metabolism and pharmacokinetics. Cytochrome P-450 of the liver plays an important role in their metabolism, but CYP1A2, CYP2C19, CYP2D6, CYP3A4 and possibly some other isoforms differ by their relative contribution. Citalopram and fluoxetine are available as racemic compounds: stereospecificity of their enantiomers has been shown for their serotonergic pharmacology, metabolism and kinetics. The pharmacokinetics of drugs may be modified in elderly patients, at different levels: absorption, distribution, metabolism and excretion. In these patients, depending on the selective serotonin reuptake inhibitor (SSRI) used, it is recommended to adapt the dose of the antidepressant: Lower doses should be used for citalopram, paroxetine and probably also for sertraline, when therapy is initiated. No clear evidence was found for fluoxetine and fluvoxamine concerning an age dependent metabolism. As elderly depressive patients may also suffer from somatic diseases, this should be considered in the choice of the dose of an SSRI, as for some of them, elimination is decreased in hepatic (citalopram, fluoxetine, fluvoxamine, sertraline) or renal (paroxetine) impairments.