Newer antidepressants are generally as efficacious as but often have fewer side effects than their predecessors such as the tricyclic antidepressants and monoamine oxidase inhibitors. These newer antidepressants include the selective serotonin reuptake inhibitors (SSRIs) citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, and sertraline; venlafaxine, a serotonin-norepinephrine reuptake inhibitor; and bupropion, a selective norepinephrine and dopamine reuptake inhibitor. Most of these antidepressants have half-lives that enable them to be administered as infrequently as 1 to 3 times per day. To further improve upon the ease of use, controlled-release formulations of bupropion, fluoxetine, paroxetine, and venlafaxine have been manufactured. Potential pharmacokinetic advantages of these formulations include lower peak plasma drug concentrations and smaller fluctuations between peak 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 discontinuation than are their immediate-release formulations. However, the rates of nausea are similar with both formulations of fluoxetine, despite higher peak plasma drug concentrations and greater fluctuation between peak and trough plasma drug concentrations with fluoxetine weekly than with fluoxetine daily. Although the connection has not been proven, more stable pharmacokinetic profiles might be the cause for the low occurrence of nausea with some controlled-release newer antidepressants.