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

Objective: To evaluate the literature comparing antidepressant effects of multiple daily dosing versus single daily dosing of antidepressants. Method: Studies comparing efficacy of single versus multiple daily dosing of antidepressants were reviewed. Data from the clinical trials meeting our inclusion criteria was subgrouped according to the half-life of the antidepressant drug studied. Meta-analyses were carried out to compare antidepressant efficacy of single versus multiple daily dosing overall and separately for the short. intermediate, and long half life antidepressant agent subgroups. Results: The review process identified 22 studies comparing the therapeutic effect 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 improvement rates in depression scores in between the two groups were almost identical (SDD versus MDD). Conclusion: This meta-analytic approach found no advantage for multiple daily dosing and suggests that sustained therapeutic serum levels are not necessary for achievement of therapeutic activity. Antidepressant benefit may simply require a limited duration of exposure above the threshold serum level. Administration of antidepressants in single daily doses appears sufficient to perturb the physiological pathways associated with depression sufficiently to achieve an adaptive therapeutic response. Moreover, a single daily dosing regimen offers the potential advantages of simplicity, increased compliance, and reduced adverse effects, which in turn would increase the overall success rate in treatment of depression. (C) 2001 Elsevier Science B.V. All rights reserved.