Administration of antidepressants - Single versus split dosing: a meta-analysis

Objective: To evaluate the literature comparing antidepressant effects of m ultiple daily dosing versus single daily dosing of antidepressants. Method: Studies comparing efficacy of single versus multiple daily dosing of antid epressants were reviewed. Data from the clinical trials meeting our inclusi on criteria was subgrouped according to the half-life of the antidepressant drug studied. Meta-analyses were carried out to compare antidepressant eff icacy of single versus multiple daily dosing overall and separately for the short. intermediate, and long half life antidepressant agent subgroups. Re sults: The review process identified 22 studies comparing the therapeutic e ffect of antidepressants according to their dosing schedules. Although most studies used antidepressant medications with short half-lives, none found a significant difference in therapeutic efficacy. Furthermore. the improvem ent rates in depression scores in between the two groups were almost identi cal (SDD versus MDD). Conclusion: This meta-analytic approach found no adva ntage for multiple daily dosing and suggests that sustained therapeutic ser um levels are not necessary for achievement of therapeutic activity. Antide pressant benefit may simply require a limited duration of exposure above th e threshold serum level. Administration of antidepressants in single daily doses appears sufficient to perturb the physiological pathways associated w ith depression sufficiently to achieve an adaptive therapeutic response. Mo reover, a single daily dosing regimen offers the potential advantages of si mplicity, increased compliance, and reduced adverse effects, which in turn would increase the overall success rate in treatment of depression. (C) 200 1 Elsevier Science B.V. All rights reserved.