A Phase 4 interventional study of Clozapine in Schizophrenia and Schizoaffective Disorder, sponsored by Centre for Addiction and Mental Health. Completed at 1 site in Canada. Open to participants aged 18 Years to 60 Years. Per ClinicalTrials.gov, last updated 2024-08-21.
Sponsored by Centre for Addiction and Mental Health · Phase 4, Interventional, and Treatment
Clozapine has been demonstrated to be clinically superior to other antipsychotics in treatment-resistant schizophrenia (TRS), and is positioned as such in treatment guidelines. Because it is relegated to use in TRS, guidelines require that it only be used after other antipsychotics have failed; accordingly, clinicians routinely contend with stopping the previous antipsychotic in making the switch to clozapine. Perhaps because of its numerous and potentially severe side effects, the issue of clozapine titration has frequently been addressed, although to our knowledge no study has, as of yet, assessed the comparability of gradual vs. immediate antipsychotic discontinuation in switching to clozapine. To address the gap in knowledge specific to clozapine, the investigators conducted a pilot, 8-week, double-blind, randomized controlled trial examining immediate vs. gradual antipsychotic discontinuation in patients with schizophrenia undergoing a switch to clozapine.
Clozapine has been demonstrated to be clinically superior to other antipsychotics in treatment-resistant schizophrenia (TRS), and is positioned as such in treatment guidelines. Because it is relegated to use in TRS, guidelines require that it only be used after other antipsychotics have failed; accordingly, clinicians routinely contend with stopping the previous antipsychotic in making the switch to clozapine. Perhaps because of its numerous and potentially severe side effects, the issue of clozapine titration has frequently been addressed, although to our knowledge no study has, as of yet, assessed the comparability of gradual vs. immediate antipsychotic discontinuation in switching to clozapine.
While the question has not been asked vis-à-vis clozapine, there have been several studies examining gradual vs. immediate antipsychotic discontinuation in switching antipsychotics. Immediate antipsychotic discontinuation is associated with the following risks: (1) withdrawal/discontinuation symptoms or rebound syndromes related to cholinergic, histaminergic, and serotonergic activity; (2) supersensitivity syndromes (e.g., withdrawal dyskinesia, supersensitivity psychosis); and (3) exacerbation/re-emergence of symptoms secondary to diminished response with newly introduced antipsychotic. On the other hand, gradual antipsychotic discontinuation is associated with the risk of worsening/emergent side effects. This said, all of the studies, including one meta-analysis, report no differences in efficacy and safety between immediate and gradual discontinuation strategies in antipsychotic switching. However, it should be also noted that all of the studies were conducted under an open-label design or a single-blind design.
To address the gap in knowledge specific to clozapine, the investigators conducted a pilot, 8-week, double-blind, randomized controlled trial examining immediate vs. gradual antipsychotic discontinuation in patients with schizophrenia undergoing a switch to clozapine.
3,471 studies on the registry are indexed under Schizophrenia; 472 are open to participants now.
This study's enrollment of 33 is below the median of 70 across 2,872 interventional studies indexed under Schizophrenia.
Browse Schizophrenia studies →Centre for Addiction and Mental Health is the lead sponsor of 327 studies on the registry; 51 are open to participants now.
Counted across the registry records on this site, refreshed daily.
Exclusion Criteria:
The antipsychotic drugs that patients took at baseline were prepared in unmarked capsules, with the dose adjusted to provide a 25% reduction weekly over the next 3 weeks. The dose tapering schedule was as follows: 3 capsules at baseline, 2 capsules at week 1, 1 capsule at week 2, and 0 capsules at week 3. All capsules contained placebo (i.e., the antipsychotic drugs were abruptly discontinued). Clozapine was gradually increased to 300 mg/day according to the following schedule: 12.5 mg/day at day 0 and increased by 25 mg/day to 300 mg/day at day 12, with this dose maintained for three weeks and thereafter adjusted according to clinical judgment. Concomitant medications were kept constant throughout the study period.
Drug: Clozapine
The antipsychotic drugs that patients took at baseline were prepared in unmarked capsules, with the dose adjusted to provide a 25% reduction weekly over the next 3 weeks. The dose tapering schedule was as follows: 3 capsules at baseline, 2 capsules at week 1, 1 capsule at week 2, and 0 capsules (i.e., the antipsychotic drugs were discontinued) at week 3. Clozapine was gradually increased to 300 mg/day according to the following schedule: 12.5 mg/day at day 0 and increased by 25 mg/day to 300 mg/day at day 12, with this dose maintained for three weeks and thereafter adjusted according to clinical judgment. Concomitant medications were kept constant throughout the study period.
Drug: Clozapine
Switching to clozapine with immediate or gradual antipsychotic discontinuation
Also known as: Clozaril
Change in the Brief Psychiatric Rating Scale (BPRS) total scores from baseline to 8 weeks
Time frame: 0 and 8 weeks
Change in the Simpson-Angus Scale (SAS) total scores from baseline to 8 weeks
Time frame: 0 and 8 weeks
Change in the Barnes Akathisia Rating Scale (BARS) total scores from baseline to 8 weeks
Time frame: 0 and 8 weeks
Change in the Abnormal Involuntary Movement Scale (AIMS) overall severity scores from baseline to 8 weeks
Time frame: 0 and 8 weeks
Change in the UKU Side Effect Rating Scale (UKU) subscale average scores from baseline to 8 weeks
Time frame: 0 and 8 weeks
Change in the Clinical Global Impression - Severity scale (CGI-S) scores from baseline to 8 weeks
Time frame: 0 and 8 weeks
Change in the Calgary Depression Scale for Schizophrenia (CDSS) total scores from baseline to 8 weeks
Time frame: 0 and 8 weeks
Change in the Drug Attitude Inventory (DAI-10) total scores from baseline to 8 weeks
Time frame: 0 and 8 weeks
Change in the Schedule for the Assessment of Insight (SAI) total scores from baseline to 8 weeks
Time frame: 0 and 8 weeks
Plan to share: No
This study is completed, as verified in Aug 2024. You cannot join it, but the record below documents what was studied.
Get an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
Centre for Addiction and Mental Health