Clinical trial NCT04478838: "Extended" (Alternate Day) Antipsychotic Dosing
Official title: "Re-examining Maintenance Antipsychotic Treatment in Schizophrenia: "Extended" Antipsychotic Dosing"
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Schizophrenia and Related Disorders
Drug Administration Schedule
Drug Therapy
Antipsychotic Agents
Keywords: Extended Dosing
Alternate day dosing
Olanzapine
Risperidone
Paliperidone
Lead sponsor: Centre for Addiction and Mental Health
Sponsor class: OTHER
First posted: 2020-07-21
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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)

Primary outcomes:
measure: Clinical Deterioration using the "Brief Psychiatric Rating Scale - Expanded"
timeFrame: 0 and 52 weeks
Secondary outcomes:
measure: Exploratory Outcomes - Symptoms 1 using "The Clinical Global Impression - Schizophrenia Scale"
timeFrame: 0 and 52 weeks
measure: Exploratory Outcomes - Symptoms/Side Effects using "The Clinical Global Impression - Schizophrenia Scale"
timeFrame: 0 and 52 weeks
measure: Exploratory Outcomes - Symptoms 3 using the "Calgary Depression Scale for Schizophrenia"
timeFrame: 0 and 52 weeks
measure: Exploratory Outcomes - Symptoms 4 using the "Yale-Brown Obsessive-Compulsive Scale"
timeFrame: 0 and 52 weeks
measure: Exploratory Outcomes - Symptoms 5 using the "Hamilton Anxiety Scale"
timeFrame: 0 and 52 weeks
measure: Exploratory Outcomes - Side Effects 1 using the "Leibowitz Social Anxiety Scale"
timeFrame: 0 and 52 weeks
measure: Exploratory Outcomes - Side Effects 2 using the "Neurological Evaluation Scale"
timeFrame: 0 and 52 weeks
measure: Exploratory Outcomes - Side Effects 3 using the "Glasgow Assessment Side-Effect Scale"
timeFrame: 0 and 52 weeks
measure: Exploratory Outcomes - Side Effects 4 using the "Drug Attitude Inventory" Scale
timeFrame: 0 and 52 weeks
measure: Exploratory Outcomes - Side Effects 5 using the "Barnes Akathisia Rating Scale"
timeFrame: 0 and 52 weeks
measure: Exploratory Outcomes - Side Effects 6 using the "Simpson Angus Scale"
timeFrame: 0 and 52 weeks
measure: Exploratory Outcomes - Side Effects 7 using the "Abnormal Involuntary Movement Scale"
timeFrame: 0 and 52 weeks
measure: Exploratory Outcomes - Wellbeing using the "Quality of Life and Satisfaction Questionnaire"
timeFrame: 0 and 52 weeks
measure: Exploratory Outcomes - Wellbeing 2 using the "Quality of Life and Satisfaction Questionnaire - Short Form"
timeFrame: 0 and 52 weeks
measure: Exploratory Outcomes - Wellbeing 3 using the "Subject Happiness Scale"
timeFrame: 0 and 52 weeks
measure: Exploratory Outcomes - Function 1 using the "Social and Occupational Function Assessment Scale"
timeFrame: 0 and 52 weeks
measure: Exploratory Outcomes - Function 2 using the "Personal and Social Performance Scale"
timeFrame: 0 and 52 weeks
measure: Exploratory Outcomes - Function 3 using the "Recovery Assessment Scale"
timeFrame: 0 and 52 weeks
Other outcomes:
Locations:
city: Toronto
country: Canada
facility: Centre for Addiction and Mental Health
state: Ontario
Study officials:
affiliation: Centre for Addiction and Mental Health
name: Gary J Remington, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: