NCT02639702

Switching From Twice-Daily to Once-Daily Clozapine Dosing in Schizophrenia

Switching From Twice-Daily to Once-Daily Clozapine Dosing in Schizophrenia: A Pilot, Double-Blind, Randomized Controlled Trial

• Status: Recruiting
• Phase: Phase 4
• Study type: Interventional
• Enrollment: 30 (estimated)
• Sponsor: Centre for Addiction and Mental Health · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

Plasma half-life has routinely been used to establish the dosing schedule of antipsychotics; for example, it is recommended that agents with a short plasma half-life be administered multiple times per day. However, to date, several randomized controlled trials (RCTs) have shown no differences in clinical outcomes between once- and twice-daily dosing of various antipsychotics, suggesting that once-daily dosing of antipsychotics is a viable option regardless of plasma half-life. This would apply to clozapine as well; however, there have been no studies comparing once-daily vs. twice-daily dosing regimens of clozapine in terms of efficacy and tolerability. To address this gap in the literature, the investigators shall conduct a pilot, double-blind, RCT to examine efficacy and tolerability following a switch to once-daily dosing regimen of clozapine in patients with schizophrenia receiving clozapine twice a day.

Detailed description

Plasma half-life has routinely been used to establish the dosing schedule of antipsychotics; for example, it is recommended that agents with a short plasma half-life be administered multiple times per day. To date, however, several randomized controlled trials (RCTs) have shown that once-daily dosing of antipsychotics including perphenazine, risperidone, olanzapine, quetiapine, and asenapine is comparable to twice-daily dosing in terms of efficacy and tolerability, suggesting that once-daily dosing of antipsychotics is a viable option regardless of plasma half-life. This issue applies to clozapine as well, in that it has a relatively short plasma half-life of 12-16 hours; of note, the product monographs recommends that clozapine be administered more than once daily if the dose exceeds 200 mg/day in Canada. Despite this, in clinical practice clozapine is frequently administered once daily because of convenience and side effects such as a daytime sedation or somnolence, In support of this, a cross-sectional survey done at the investigators' own centre has revealed that clozapine was prescribed once daily in 75.1% of 676 patients, even though \>200 mg/day was administered in 88.6%. However, there have been no studies comparing once-daily vs. twice-daily dosing regimens of clozapine in terms of efficacy and tolerability. To address this gap in the literature, the investigators shall conduct a pilot, double-blind, RCT to examine efficacy and tolerability following a switch to once-daily dosing regimen of clozapine in patients with schizophrenia receiving clozapine twice a day.

Conditions

• Schizophrenia
• Schizoaffective Disorder

Interventions

Type	Name	Description
DRUG	Clozapine	Switching from twice-daily to once-daily clozapine dosing regimen

Timeline

• Start date: 2016-08-01
• Primary completion: 2026-12-01
• Completion: 2026-12-01
• First posted: 2015-12-24
• Last updated: 2023-09-07

Locations

1 site across 1 country: Canada