"Extended" (Alternate Day) Antipsychotic Dosing

NCT ID: NCT04478838

Last Updated: 2025-05-04

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE4

Total Enrollment

120 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-06-06

Study Completion Date

2028-09-30

Brief Summary

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The study wishes to examine whether "extended" antipsychotic treatment, in this case, antipsychotic treatment every other day, is as effective as daily treatment. It is also evaluating whether there may be differences in terms of side effects.

Participants will be randomly assigned to either the treatment as usual group (i.e., taking antipsychotic daily) or the extended dosing group (i.e., taking antipsychotic one day on, one day off). That means, like flipping a coin, there is a 50/50 chance that participants will continue on daily dosing of your antipsychotic or have it switched to every other day dosing.

This study will last for 1 year. Participants will be evaluated at the beginning and every two weeks during the first 6 months, with visits once every 4 weeks for the final 6 months. In total, participants will make 22 visits over 52 weeks to the investigator's office.

The investigators hypothesize that with ED, there will be no change in symptom severity but improvement in the frequency and severity of side effects, wellbeing, and functioning.

Detailed Description

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This is a randomized, double-blind, controlled trial that will compare ED, i.e. alternate day dosing to daily dosing i.e. TAU.

Individuals will be randomized to ED or TAU using a permuted block design with a random number generator. The size will be fixed and study personnel blinded to the randomization block size.

To maintain a double-blind design, our pharmacy will provide, on an individualized basis, APs at the appropriate dose and placebo where necessary in matching gelatin capsules, packaged in blister packs. The active tablet will be over-encapsulated, and matching placebo will be prepared using the same capsules (filled with lactose). Thus, from the individual subject's position, AP treatment is continued according to the same daily schedule. Further, if their current medication is prescribed in divided doses, this too will be employed during the study. The minimum and maximum doses for Risperidone will be 1 mg and 16mg respectively. The minimum and maximum doses for Olanzapine will be 5 mg and 20mg respectively. The minimum and maximum doses for Paliperidone will be 3 mg and 12mg respectively. Other psychotropic medications prescribed before the study will be permitted, with any changes in dosing during its course documented

The trial is 1 year in duration. To prevent bias, the study code will remain blinded until the trial's completion.

Study visits will be scheduled every 2 weeks over the first 6 months, in line with the earlier investigation. Thereafter, the visits will be decreased to every 4 weeks, aligning with the schedule routinely observed in our ambulatory clinics.

The investigators are asking the following questions:

1. (Non-inferiority) Can additional confirmatory evidence support "extended" AP dosing (ED) as an alternative to continuous administration, i.e. is it as effective clinically?
2. (Superiority) Can the investigators establish clinical benefits (e.g. better tolerability, fewer side effects, such as decreased glucose dysregulation) with ED?

Hypothesis: The investigators hypothesize that with ED, there will be no change in symptom severity but improvement in the frequency and severity of side effects, wellbeing, and functioning.

Conditions

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Schizophrenia and Related Disorders Drug Administration Schedule Drug Therapy Antipsychotic Agents

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Extended Dosing Group

Participants taking olanzapine or risperidone or paliperidone will be switched to an alternate day dosing schedule.

Group Type EXPERIMENTAL

Risperidone

Intervention Type DRUG

0.25 mg, 0.5 mg, 1 mg, 2 mg, 3 mg and 4 mg Tablets

Olanzapine

Intervention Type DRUG

2.5 mg, 5 mg, 7.5 mg, 10 mg, 15 mg, 20 mg Tablets

paliperidone

Intervention Type DRUG

3 mg, 6 mg, 9 mg Tablets

Treatment as Usual group

Participants will continue to take their olanzapine or risperidone or paliperidone following the same prescribed daily schedule.

Group Type NO_INTERVENTION

No interventions assigned to this group

Interventions

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Risperidone

0.25 mg, 0.5 mg, 1 mg, 2 mg, 3 mg and 4 mg Tablets

Intervention Type DRUG

Olanzapine

2.5 mg, 5 mg, 7.5 mg, 10 mg, 15 mg, 20 mg Tablets

Intervention Type DRUG

paliperidone

3 mg, 6 mg, 9 mg Tablets

Intervention Type DRUG

Other Intervention Names

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Risperdal Zyprexa Apo-Olanzapine Sandoz-Olanzapine Invega

Eligibility Criteria

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Inclusion Criteria

(i) A primary diagnosis of a Schizophrenia Spectrum or Other Psychotic Disorder as defined by the DSM-5 diagnosis and confirmed by the MINI (Version 7.0.2)

(ii) age 18 or older

(iii) female participants of childbearing potential must be using a reliable method of contraception and have a negative pregnancy test at the time of enrolment and must, in the investigator's opinion, practice a clinically accepted, reliable method of contraception during this study. Male participants must not father a baby during their time in the study

(iv) ability to communicate in English

(v) capacity to provide written, informed consent, as assessed using the MacCAT-CR at time of consent

(vi) stabilized as outpatients with a single oral AP (risperidone or olanzapine or paliperidone\*) at the same dose for ≥3 months i. On a prescribed risperidone dose of between 1-6mg, or a prescribed olanzapine dose of between 5-20mg, or a prescribed paliperidone 3-12mg

(vii) evidence of adherence with current AP treatment

Exclusion Criteria

(i) exposure to a depot AP within 1 year (i.e., no depot AP injection within the last year)

(ii) Current diagnosis of substance use disorder according to DSM-5 criteria (verified through the MINI for Psychotic Disorders (Version 7.0.2) and a positive drug screen for street and /or prescription drugs not prescribed to the participant by treating physicians

(iii) ECT within the last 3 months

(iv) pregnancy or lactation

(v) neurological condition (dementia including Alzheimer's disease, multiple sclerosis, epilepsy, stroke, or traumatic brain injury)

(vi) allergy to the study drugs and their excipients

(vii) allergy (e.g., galactosaemia) or severe intolerance to lactose

(viii) negative urine drug screen result for Olanzapine or Risperidone or Paliperidone (if applicable)
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Centre for Addiction and Mental Health

OTHER

Sponsor Role lead

Responsible Party

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Gary Remington

Senior Scientist

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Gary J Remington, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Centre for Addiction and Mental Health

Locations

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Centre for Addiction and Mental Health

Toronto, Ontario, Canada

Site Status RECRUITING

Countries

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Canada

Central Contacts

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Carol Borlido

Role: CONTACT

416-535-8501 ext. 34321

Gary Remington, MD, PhD

Role: CONTACT

416-535-8501 ext. 34750

Facility Contacts

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Gary J Remington, MD, PhD

Role: primary

416-535-8501 ext. 34750

Carol Borlido

Role: backup

416-535-8501 ext. 34321

Other Identifiers

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154-2018

Identifier Type: -

Identifier Source: org_study_id

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