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"Extended" (Alternate Day) Antipsychotic Dosing

C

Center for Addiction and Mental Health (CAMH)

Status and phase

Enrolling
Phase 4

Conditions

Drug Therapy
Antipsychotic Agents
Schizophrenia and Related Disorders
Drug Administration Schedule

Treatments

Drug: paliperidone
Drug: Olanzapine
Drug: Risperidone

Study type

Interventional

Funder types

Other

Identifiers

NCT04478838
154-2018

Details and patient eligibility

About

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.

Full description

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.

Enrollment

120 estimated patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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)

Trial design

Primary purpose

Treatment

Allocation

Randomized

Interventional model

Parallel Assignment

Masking

Quadruple Blind

120 participants in 2 patient groups

Extended Dosing Group
Experimental group
Description:
Participants taking olanzapine or risperidone or paliperidone will be switched to an alternate day dosing schedule.
Treatment:
Drug: Olanzapine
Drug: Risperidone
Drug: paliperidone
Treatment as Usual group
No Intervention group
Description:
Participants will continue to take their olanzapine or risperidone or paliperidone following the same prescribed daily schedule.

Trial contacts and locations

1

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Central trial contact

Gary Remington, MD, PhD; Carol Borlido

Data sourced from clinicaltrials.gov

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