Schizoaffective Disorder, Schizophrenia
Conditions
Keywords
Clozapine, Dosing, Once daily, Regimen, Schizophrenia
Brief 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.
Interventions
DRUGClozapine
Switching from twice-daily to once-daily clozapine dosing regimen
Sponsors
Centre for Addiction and Mental Health
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Diagnosed with schizophrenia or schizoaffective disorder based on DSM-IV criteria * Outpatient status * Ages 18 years or older * Has received clozapine twice a day, one of which is in the evening/bedtime, at the same dose and dosing regimen for at least 3 months * Fluent in English and competent to provide written informed consent
Exclusion criteria
* Having significant medical or neurological illnesses * Pregnant or lactating
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Brief Psychiatric Rating 18 item Scale (BPRS 18 item scale) | 0 and 12 weeks | Change in BPRS total scores from baseline to 12 weeks Total scores range from 18-126, higher scores represent worse clinical outcomes: \<31 = Illness not significant \>=31 = Mildly ill \>41 = Moderately ill \>53 = Markedly ill. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Glasgow Antipsychotic Side-effect Scale for Clozapine (GASS-C) | 0 and 12 weeks | Detect side effects related to Clozapine from baseline to 12 weeks Higher Scores indicating worse side-effects: 0-16 (absent/mild side-effects) 17-32 (moderate side-effects) 33-48 (severe side-effects) |
| Brief Evaluation of Psychosis Symptom Domains (BE-PSD) | 0 and 12 weeks | Assess the overall severity of five symptom domains of BE-PSD with a total score in each domain scoring from absent to very severe (i.e. 0-6 with higher scores with worse outcomes) |
| Personal and Social Performance scale (PSP) | 0 and 12 weeks | Change in patients social functioning scores from baseline to 12 weeks The PSP is a 100-point single item rating scale from 1-100, subdivided into 10 equal intervals with higher scores indicating better outcomes. The ratings are based on patient's functioning in four main areas: 1) socially useful activities, 2) personal and social relationships, 3) self-care; and 4) disturbing and aggressive behaviours. |
| Clinical Global Impression - Severity of Illness (CGI-S) | 0 and 12 weeks | Assess severity of Illness in Schizophrenia CGI scores from baseline to 12 weeks Scores ranging from normal to the most ill (i.e., scores ranging from 1-7 with higher scores with illness worsening) |
| Brief Neurocognitive Assessment (BNA) | 0 and 12 weeks | The BNA is a brief neurocognitive assessment that measures global cognitive impairment in patients with schizophrenia from baseline to 12 weeks. Negative Z scores (i.e., -0.5 to -2.0 ) indicate mild to severe cognitive impairment. |
| Change in the Visual Analogue Scale for Distress Associated with Symptoms (VAS-DAS) scores from baseline to 12 weeks | 0 and 12 weeks | Assess changes in level of distress associated with symptoms from no distress to worst distress (i.e., 0-100) |
| Subjective Well-being under Neuroleptics scale - Short form (SWNS) | 0 and 12 weeks | Self report scale to measure well being. Study assess changes in subjective wellbeing in patients on a neuroleptic from baseline to Week 12. Higher total score indicating better outcomes |
Countries
Canada
Contacts
CONTACTGary Remington, MD, PhD
CONTACTCarol Borlido, BSc
PRINCIPAL_INVESTIGATORGary Remington, MD, PhD
Centre for Addiction and Mental Health
Outcome results
None listed