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Immediate-Release Versus Controlled-Release Formulations: Pharmacokinetics of Newer Antidepressants in Relation to Nausea

C. Lindsay DeVane, PharmD

Published: December 1, 2003

Article Abstract

Newer antidepressants are generally as efficacious as but often have fewer side effects than theirpredecessors such as the tricyclic antidepressants and monoamine oxidase inhibitors. These newerantidepressants include the selective serotonin reuptake inhibitors (SSRIs) citalopram, escitalopram,fluoxetine, fluvoxamine, paroxetine, and sertraline; venlafaxine, a serotonin-norepinephrine reuptakeinhibitor; and bupropion, a selective norepinephrine and dopamine reuptake inhibitor. Most of theseantidepressants have half-lives that enable them to be administered as infrequently as 1 to 3 times perday. To further improve upon the ease of use, controlled-release formulations of bupropion, fluoxetine,paroxetine, and venlafaxine have been manufactured. Potential pharmacokinetic advantages ofthese formulations include lower peak plasma drug concentrations and smaller fluctuations betweenpeak and trough plasma drug concentrations, which might influence the tolerability of these medications.Tolerability advantages seen with some of these medications include diminished nausea.The 3 controlled-release agents that are designed to be taken daily—bupropion, paroxetine, and venlafaxine—are associated with lower incidences of nausea overall and nausea leading to treatment discontinuationthan are their immediate-release formulations. However, the rates of nausea are similarwith both formulations of fluoxetine, despite higher peak plasma drug concentrations and greater fluctuationbetween peak and trough plasma drug concentrations with fluoxetine weekly than with fluoxetinedaily. Although the connection has not been proven, more stable pharmacokinetic profiles mightbe the cause for the low occurrence of nausea with some controlled-release newer antidepressants.

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