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Single Versus Multiple Daily Dosing Regimens of Psychotropic Drugs for Psychiatric Disorders: A Systematic Review and Meta-Analysis

Yuhei Kikuchi, MDa,b; Yutaro Shimomura, MDa,c; Takefumi Suzuki, MD, PhDd; Hiroyuki Uchida, MD, PhDa; Masaru Mimura, MD, PhDa; and Hiroyoshi Takeuchi, MD, PhDa,*

Published: February 23, 2021


Objective: To compare efficacy and safety of single daily dosing (Single-DD) vs multiple daily dosing (Multiple-DD) regimens of psychotropic drugs, the authors conducted a systematic review and meta-analysis.

Data Sources: A systematic literature search of MEDLINE and Embase was conducted with keywords related to dosing regimens and psychotropic drugs (last search: December 30, 2019)

Study Selection: Randomized controlled trials comparing clinical outcomes between Single-DD and Multiple-DD of the same formulation of the same psychotropic drugs in patients with psychiatric disorders were included.

Data Extraction: Data on study discontinuation, psychopathology, and treatment-emergent adverse events (TEAEs) were extracted.

Results: A total of 32 studies with 34 paired comparisons involving 3,142 patients met the eligibility criteria and were included in the meta-analysis. Various types of psychotropic drugs were examined: antidepressants (22 comparisons), antipsychotics (7 comparisons), benzodiazepines (2 comparisons), mood stabilizers (2 comparisons), and antidepressant-benzodiazepine combination (1 comparison). There was no significant difference in study discontinuation due to all causes (30 comparisons, N = 2,883, risk ratio [RR] = 1.01, 95% CI = 0.94 to 1.09, P = .77), lack of efficacy (22 comparisons, N = 2,307, RR = 1.06, 95% CI = 0.84 to 1.33, P = .62), or adverse events (25 comparisons, N = 2,571, RR = 0.93, 95% CI = 0.75 to 1.14, P = .47) between the Single-DD and Multiple-DD groups. No significant difference was found in changes in psychopathology (8 comparisons, N = 1,337, standardized mean difference = 0.00, 95% CI = −0.11 to 0.11, P = .99) between the 2 groups. These results were also true for any type of psychotropic drugs. In terms of TEAEs, however, there were significant differences in anxiety (4 comparisons, N = 347, RR = 0.53, 95% CI = 0.33 to 0.84, P = .007) and sleepiness (3 comparisons, N = 934, RR = 0.82, 95% CI = 0.68 to 0.99, P = .04) in favor of the Single-DD group.

Conclusions: The findings suggest Single-DD can be clinically adopted regardless of type of psychotropic drugs in patients with psychiatric disorders in general.

Volume: 82

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