Extended-release formulations of antidepressants have been marketed as a strategy to increase patient adherence. Changes in the formulation of drugs, however, could be related to changes in efficacy and tolerability. Among second-generation antidepressants bupropion, fluoxetine, mirtazapine, paroxetine, and venlafaxine are available in immediate- and extended-release formulations.

To compare the efficacy, tolerability, and adherence of immediate- versus extended-release formulations of second-generation antidepressants for the treatment of major depressive disorder (MDD) in adults.

To provide an evidence base for clinicians when choosing immediate- or extended-release formulations for the treatment of MDD.

We conducted a comparative effectiveness review for the U.S. Agency for Healthcare Research and Quality searching PubMed, EMBASE, the Cochrane Library, PsycINFO, and International Pharmaceutical Abstracts up to January 2011. Two persons independently reviewed the literature, abstracted data, and rated the risk of bias.

Six RCTs and one retrospective cohort study provided evidence about the comparative efficacy, tolerability, and adherence of bupropion XL (extended release) versus bupropion SR (sustained release), fluoxetine daily versus fluoxetine weekly, paroxetine IR (immediate release) versus paroxetine CR (continuous release), and venlafaxine IR versus venlafaxine XR (extended release). Overall, no substantial differences in efficacy and safety could be detected. Open-label and observational evidence indicated better adherence for bupropion XL and fluoxetine weekly than for immediate-release medications. No differences in adherence could be detected between paroxetine IR and paroxetine CR.

Our findings indicate similar efficacy and tolerability between immediate- and extended-release formulations. Whether extended-release formulations lead to better adherence remains unclear.