Clozapine Once-Daily Versus Divided Dosing Regimen

Abstract

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Comparison of the Effectiveness and Safety of Clozapine Between Once-Daily and Divided Dosing Regimen in Patients With Treatment-Resistant Schizophrenia

“…They found that twice-daily dosing of clozapine theoretically achieved a therapeutic plasma concentration more often than a once-daily dosing regimen. 8 However, similarly to the current study, Kitagawa et al 11 found that the psychiatric symptoms and adverse effects of clozapine did not differ significantly between once-daily and divided dosing regimens. The reason for the effectiveness of once-daily dosing, which was not inferior to divided dosing of clozapine, despite clozapine having a short half-life of 12 hours, may be that there was a slower reduction of central D2 receptor occupancy compared to that observed at antipsychotic blood concentration.…”

“…These results may be explained by a previous study that found that the peak and trough plasma concentration of clozapine at steady state did not differ significantly between once-daily and divided dosing regimens. 11 Furthermore, this study found that although the median dose of clozapine in the divided dosing group was significantly greater than in the once-daily dosing group, the efficacy was not different between groups. Second, the nonadherence rate was higher in the divided dosing group than in the once-daily dosing group; however, the difference was not statistically significant.…”

“…In addition, a cross-sectional study comparing the actual plasma concentration of clozapine achieved by once-daily and divided dosing regimens in patients with schizophrenia or schizoaffective disorders found no difference in psychotic symptom resolution, adverse effects, or peak/trough plasma concentration between once-daily and divided dosing regimens. 11 Because of the limitations of the cross-sectional study design, it is difficult to determine any causal relationship between the dosing regimen of clozapine and clinical outcome. In addition, there have not been any studies comparing all-cause discontinuation between the once-daily and divided dosing regimens.…”

Dosing options for clozapine

“…1,2 Investigators recently conducted a study to evaluate whether a significant difference in achievable plasma concentration profile exists between the two clozapine dosage regimens, and, if present, whether the difference has implications for the drug's efficacy and toxicity. 3…”

Once‐ versus multiple‐daily dosing of clozapine

“…Although clozapine is widely used in patients with treatment‐resistant schizophrenia, there remains relatively little agreement on the comparative effectiveness of once‐ versus multiple‐daily dosing (Kikuchi, et al, 2021; Kitagawa et al, 2022). While the relatively short elimination half‐life of clozapine would seem to favor a multiple‐daily dosing regimen, once‐daily dosing would encourage medication adherence.…”