<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT04478838</url>
  </required_header>
  <id_info>
    <org_study_id>154-2018</org_study_id>
    <nct_id>NCT04478838</nct_id>
  </id_info>
  <brief_title>&quot;Extended&quot; (Alternate Day) Antipsychotic Dosing</brief_title>
  <official_title>&quot;Re-examining Maintenance Antipsychotic Treatment in Schizophrenia: &quot;Extended&quot; Antipsychotic Dosing&quot;</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Centre for Addiction and Mental Health</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Centre for Addiction and Mental Health</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The study wishes to examine whether &quot;extended&quot; antipsychotic treatment, in this case,&#xD;
      antipsychotic treatment every other day, is as effective as daily treatment. It is also&#xD;
      evaluating whether there may be differences in terms of side effects.&#xD;
&#xD;
      Participants will be randomly assigned to either the treatment as usual group (i.e., taking&#xD;
      antipsychotic daily) or the extended dosing group (i.e., taking antipsychotic one day on, one&#xD;
      day off). That means, like flipping a coin, there is a 50/50 chance that participants will&#xD;
      continue on daily dosing of your antipsychotic or have it switched to every other day dosing.&#xD;
&#xD;
      This study will last for 1 year. Participants will be evaluated at the beginning and every&#xD;
      two weeks during the first 6 months, with visits once every 4 weeks for the final 6 months.&#xD;
      In total, participants will make 22 visits over 52 weeks to the investigator's office.&#xD;
&#xD;
      The investigators hypothesize that with ED, there will be no change in symptom severity but&#xD;
      improvement in the frequency and severity of side effects, wellbeing, and functioning.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a randomized, double-blind, controlled trial that will compare ED, i.e. alternate day&#xD;
      dosing to daily dosing i.e. TAU.&#xD;
&#xD;
      Individuals will be randomized to ED or TAU using a permuted block design with a random&#xD;
      number generator. The size will be fixed and study personnel blinded to the randomization&#xD;
      block size.&#xD;
&#xD;
      To maintain a double-blind design, our pharmacy will provide, on an individualized basis, APs&#xD;
      at the appropriate dose and placebo where necessary in matching gelatin capsules, packaged in&#xD;
      blister packs. The active tablet will be over-encapsulated, and matching placebo will be&#xD;
      prepared using the same capsules (filled with lactose). Thus, from the individual subject's&#xD;
      position, AP treatment is continued according to the same daily schedule. Further, if their&#xD;
      current medication is prescribed in divided doses, this too will be employed during the&#xD;
      study. The minimum and maximum doses for Risperidone will be 1 mg and 16mg respectively. The&#xD;
      minimum and maximum doses for Olanzapine will be 5 mg and 20mg respectively. Other&#xD;
      psychotropic medications prescribed before the study will be permitted, with any changes in&#xD;
      dosing during its course documented&#xD;
&#xD;
      The trial is 1 year in duration. To prevent bias, the study code will remain blinded until&#xD;
      the trial's completion.&#xD;
&#xD;
      Study visits will be scheduled every 2 weeks over the first 6 months, in line with the&#xD;
      earlier investigation. Thereafter, the visits will be decreased to every 4 weeks, aligning&#xD;
      with the schedule routinely observed in our ambulatory clinics.&#xD;
&#xD;
      The investigators are asking the following questions:&#xD;
&#xD;
        1. (Non-inferiority) Can additional confirmatory evidence support &quot;extended&quot; AP dosing (ED)&#xD;
           as an alternative to continuous administration, i.e. is it as effective clinically?&#xD;
&#xD;
        2. (Superiority) Can the investigators establish clinical benefits (e.g. better&#xD;
           tolerability, fewer side effects, such as decreased glucose dysregulation) with ED?&#xD;
&#xD;
      Hypothesis: The investigators hypothesize that with ED, there will be no change in symptom&#xD;
      severity but improvement in the frequency and severity of side effects, wellbeing, and&#xD;
      functioning.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">June 6, 2022</start_date>
  <completion_date type="Anticipated">September 30, 2028</completion_date>
  <primary_completion_date type="Anticipated">September 30, 2027</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Clinical Deterioration using the &quot;Brief Psychiatric Rating Scale - Expanded&quot;</measure>
    <time_frame>0 and 52 weeks</time_frame>
    <description>Change in the Brief Psychiatric Rating Scale - total scores from baseline to 52 weeks. The score values for each item on the BPRS range from 1 to 7. The higher the score for each item the worse the outcome. The values for each item on the BPRS are scored as follows:&#xD;
1- Not Present, 2 - Very Mild, 3- Mild, 4- Moderate, 5 - Moderately Severe, 6- Severe, 7- Very Severe.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Exploratory Outcomes - Symptoms 1 using &quot;The Clinical Global Impression - Schizophrenia Scale&quot;</measure>
    <time_frame>0 and 52 weeks</time_frame>
    <description>Change in Clinical Global Impression - Schizophrenia (CGI-SCH) severity of illness scores from baseline to 52 weeks. The severity of illness score values for each item on the CGI- SCH range from 1 to 7. The higher the score for each item the worse the outcome.&#xD;
The severity of illness values are scored as follows:&#xD;
1- Normal, not ill, 2 -Minimally ill, 3- Mildly ill, 4- Moderately ill, 5 - Markedly ill, 6- Severely ill, 7- Among the most severely ill.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Exploratory Outcomes - Symptoms/Side Effects using &quot;The Clinical Global Impression - Schizophrenia Scale&quot;</measure>
    <time_frame>0 and 52 weeks</time_frame>
    <description>Change in Clinical Global Impression - Schizophrenia Scale (CGI-SCH) degree of change scores from baseline to 52. The values range from 1-7. The higher the score for each item the worse the outcome. The score value of each item are as follows:&#xD;
1 - Very much improved, 2 - Much Improved, 3 - Minimally improved, 4 - No Change, 5 - Minimally Worse, 6- Much Worse, 7 - Very Much Worse</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Exploratory Outcomes - Symptoms 3 using the &quot;Calgary Depression Scale for Schizophrenia&quot;</measure>
    <time_frame>0 and 52 weeks</time_frame>
    <description>Change in Calgary Depression Scale (CDS) scores from baseline to 52 weeks. Scores range from 0-3 as follows: 0- Absent, 1- Mild, 2- Moderate, 3 - Severe. The higher the score for each item, the worse the outcome.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Exploratory Outcomes - Symptoms 4 using the &quot;Yale-Brown Obsessive-Compulsive Scale&quot;</measure>
    <time_frame>0 and 52 weeks</time_frame>
    <description>Change in Yale-Brown Obsessive-Compulsive Scale (YBOCS) scores from baseline to 52 weeks. Scores range from 0-4 with higher scores indicating worsening of outcome.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Exploratory Outcomes - Symptoms 5 using the &quot;Hamilton Anxiety Scale&quot;</measure>
    <time_frame>0 and 52 weeks</time_frame>
    <description>Change in Hamilton Anxiety Scale (HAM-A) scores from baseline to 52 weeks. Scores on each item range from 0-4 as follows: 0- not present, 1- mild, 2 - moderate, 3- severe, 4 - very severe. Higher scores on each item and total score indicate worsening of anxiety outcome.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Exploratory Outcomes - Side Effects 1 using the &quot;Leibowitz Social Anxiety Scale&quot;</measure>
    <time_frame>0 and 52 weeks</time_frame>
    <description>Change in Liebowitz Social Anxiety Scale (LSAS) scores from baseline to 52 weeks. For each item, there are 2 scores; 1) score for fear of anxiety and 2) score for avoidance. For the fear of anxiety component of the scale, score ranges from 0-3 as follows: 0- None, 1- Mild, 2- Moderate, 3 - Severe. The scores for the Avoidance component of the scale ranges from 0-3 as follows: 0 - Never, 1- Occasionally, 2 - Often, 3 - Usually. The higher the score the worse the outcome.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Exploratory Outcomes - Side Effects 2 using the &quot;Neurological Evaluation Scale&quot;</measure>
    <time_frame>0 and 52 weeks</time_frame>
    <description>Change in Neurological Evaluation Scale (NES) scores from baseline to 52 weeks. There are 12 items and scores for each item range from 0-2 with higher scores indicating worsening of outcome. Item 5 does not require a score.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Exploratory Outcomes - Side Effects 3 using the &quot;Glasgow Assessment Side-Effect Scale&quot;</measure>
    <time_frame>0 and 52 weeks</time_frame>
    <description>Change in Glasgow Assessment Side-Effect Scale (GASS) scores from baseline to 52 weeks. Scores range from 0-3 as follows: 0 -Never, 1- Once, 2 - A few times, 3 - Everyday. The higher the score for each item and higher total indicates a worse side effect outcome.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Exploratory Outcomes - Side Effects 4 using the &quot;Drug Attitude Inventory&quot; Scale</measure>
    <time_frame>0 and 52 weeks</time_frame>
    <description>Change in Drug Attitude Inventory (DAI) scores from baseline to 52 weeks. Scores are based on 30 true/false statements.There are 15 items that a patient who is fully adherent to their prescribed medication (and so would be expected to have a positive response to medication would answer true and 15 items such a patient would answer as false. Each positive answer is given a score of plus one, and each negative answer is given a score of minus one. The total positive score would indicate a positive response (adherent to medication) whereas a negative total score would indicate a negative response (non adherent to medication).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Exploratory Outcomes - Side Effects 5 using the &quot;Barnes Akathisia Rating Scale&quot;</measure>
    <time_frame>0 and 52 weeks</time_frame>
    <description>Change in Barnes Akathisia Rating Scale (BARS) scores from baseline to 52 weeks. The total score for the global clinical assessment of akathisia ranges from 0-5 with higher score indicating a worsening of akathisia.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Exploratory Outcomes - Side Effects 6 using the &quot;Simpson Angus Scale&quot;</measure>
    <time_frame>0 and 52 weeks</time_frame>
    <description>Change in Simpson Angus Scale (SAS) scores from baseline to 52 weeks. There are 13 items in the scale; scores on each item range from 0-4 with higher scores indicating worse extrapyramidal outcome.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Exploratory Outcomes - Side Effects 7 using the &quot;Abnormal Involuntary Movement Scale&quot;</measure>
    <time_frame>0 and 52 weeks</time_frame>
    <description>Change in Abnormal Involuntary Movement Scale (AIMS) scores from baseline to 52 weeks. There are 13 items in the scale, scores on each item range from 0-4 with higher scores indicating a worse outcome in abnormal movements.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Exploratory Outcomes - Wellbeing using the &quot;Quality of Life and Satisfaction Questionnaire&quot;</measure>
    <time_frame>0 and 52 weeks</time_frame>
    <description>Change in Quality of Life Scale (QLS) scores from baseline to 52 weeks. The scores for each item range from 0-6. The higher the score, the better the outcome. On several items, there is an additional score of &quot;9&quot; to indicate &quot;not applicable&quot;.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Exploratory Outcomes - Wellbeing 2 using the &quot;Quality of Life and Satisfaction Questionnaire - Short Form&quot;</measure>
    <time_frame>0 and 52 weeks</time_frame>
    <description>Change in Quality of Life and Satisfaction Questionnaire - Short Form (Q-LES-Q-SF) scores from baseline to 52 weeks. Scores range from 0-6 with lower scores indicating a worse outcome.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Exploratory Outcomes - Wellbeing 3 using the &quot;Subject Happiness Scale&quot;</measure>
    <time_frame>0 and 52 weeks</time_frame>
    <description>.Change in Subjective Happiness Scale (SHS) scores from baseline to 52 weeks. There are 4 items; scores on each item range from 1-7 with higher scores indicating a happier outcome.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Exploratory Outcomes - Function 1 using the &quot;Social and Occupational Function Assessment Scale&quot;</measure>
    <time_frame>0 and 52 weeks</time_frame>
    <description>Change in : Social and Occupational Function Assessment Scale (SOFAS). scores from baseline to 52 weeks. A total score ranges from 0-100 with higher scores indicating better social and occupational functioning..</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Exploratory Outcomes - Function 2 using the &quot;Personal and Social Performance Scale&quot;</measure>
    <time_frame>0 and 52 weeks</time_frame>
    <description>Change in Personal and Social Performance scale (PSP) scores from baseline to 52 weeks. The ratings are based on four areas (a) socially useful activities, including work and study; b) personal and social relationships; c) self, and d) disturbing and aggressive behaviours. Overall score range from 1-100. The higher the overall rating, the better the outcome. The breakdown of the total Rating score are as follows: scores ranging from 1-30 reflect functioning so poor that intensive support or supervision is needed; ratings from 31-70 reflect manifest disabilities of various degrees; ratings from 71-100 reflect only mild difficulties.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Exploratory Outcomes - Function 3 using the &quot;Recovery Assessment Scale&quot;</measure>
    <time_frame>0 and 52 weeks</time_frame>
    <description>Change in Recovery Assessment Scale (RAS) scores from baseline to 52 weeks. There are 41 items with scores on each item ranging from 1-5 with higher scores indicating better outcomes.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">120</enrollment>
  <condition>Schizophrenia and Related Disorders</condition>
  <condition>Drug Administration Schedule</condition>
  <condition>Drug Therapy</condition>
  <condition>Antipsychotic Agents</condition>
  <arm_group>
    <arm_group_label>Extended Dosing Group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants taking olanzapine or risperidone will be switched to an alternate day dosing schedule.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Treatment as Usual group</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>Participants will continue to take their olanzapine or risperidone following the same prescribed daily schedule.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Risperidone</intervention_name>
    <description>0.25 mg, 0.5 mg, 1 mg, 2 mg, 3 mg and 4 mg Tablets</description>
    <arm_group_label>Extended Dosing Group</arm_group_label>
    <other_name>Risperdal</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Olanzapine</intervention_name>
    <description>2.5 mg, 5 mg, 7.5 mg, 10 mg, 15 mg, 20 mg Tablets</description>
    <arm_group_label>Extended Dosing Group</arm_group_label>
    <other_name>Zyprexa</other_name>
    <other_name>Apo-Olanzapine</other_name>
    <other_name>Sandoz-Olanzapine</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        (i) A primary diagnosis of a Schizophrenia Spectrum or Other Psychotic Disorder as defined&#xD;
        by the DSM-5 diagnosis and confirmed by the MINI (Version 7.0.2)&#xD;
&#xD;
        (ii) age 18 or older&#xD;
&#xD;
        (iii) female participants of childbearing potential must be using a reliable method of&#xD;
        contraception and have a negative pregnancy test at the time of enrolment and must, in the&#xD;
        investigator's opinion, practice a clinically accepted, reliable method of contraception&#xD;
        during this study. Male participants must not father a baby during their time in the study&#xD;
&#xD;
        (iv) ability to communicate in English&#xD;
&#xD;
        (v) capacity to provide written, informed consent, as assessed using the MacCAT-CR at time&#xD;
        of consent&#xD;
&#xD;
        (vi) stabilized as outpatients with a single oral AP (risperidone or olanzapine*) at the&#xD;
        same dose for ≥3 months i. On a prescribed risperidone dose of between 1-6mg, or a&#xD;
        prescribed olanzapine dose of between 5-20mg&#xD;
&#xD;
        (vii) evidence of adherence with current AP treatment&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        (i) exposure to a depot AP within 1 year (i.e., no depot AP injection within the last year)&#xD;
&#xD;
        (ii) Current diagnosis of substance use disorder according to DSM-5 criteria (verified&#xD;
        through the MINI for Psychotic Disorders (Version 7.0.2) and a positive drug screen for&#xD;
        street and /or prescription drugs not prescribed to the participant by treating physicians&#xD;
&#xD;
        (iii) ECT within the last 3 months&#xD;
&#xD;
        (iv) pregnancy or lactation&#xD;
&#xD;
        (v) neurological condition (dementia including Alzheimer's disease, multiple sclerosis,&#xD;
        epilepsy, stroke, or traumatic brain injury)&#xD;
&#xD;
        (vi) allergy to the study drugs and their excipients&#xD;
&#xD;
        (vii) allergy or intolerance to lactose&#xD;
&#xD;
        (viii) negative urine drug screen result for Olanzapine or Risperidone&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Gary J Remington, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Centre for Addiction and Mental Health</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Carol Borlido</last_name>
    <phone>416-535-8501</phone>
    <phone_ext>30547</phone_ext>
    <email>carol.borlido@camh.ca</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Gary Remington, MD, PhD</last_name>
    <phone>416-535-8501</phone>
    <phone_ext>34750</phone_ext>
    <email>gary.remington@camh.ca</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Centre for Addiction and Mental Health</name>
      <address>
        <city>Toronto</city>
        <state>Ontario</state>
        <zip>M5T 1R8</zip>
        <country>Canada</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Gary J Remington, MD, PhD</last_name>
      <phone>416-535-8501</phone>
      <phone_ext>34750</phone_ext>
      <email>gary.remington@camh.ca</email>
    </contact>
    <contact_backup>
      <last_name>Carol Borlido</last_name>
      <phone>416-535-8501</phone>
      <phone_ext>34321</phone_ext>
      <email>caro.borlido@camh.ca</email>
    </contact_backup>
    <investigator>
      <last_name>Gary J Remington, MD, PhD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>Canada</country>
  </location_countries>
  <verification_date>August 2023</verification_date>
  <study_first_submitted>July 16, 2020</study_first_submitted>
  <study_first_submitted_qc>July 16, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 21, 2020</study_first_posted>
  <last_update_submitted>August 31, 2023</last_update_submitted>
  <last_update_submitted_qc>August 31, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">September 5, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Centre for Addiction and Mental Health</investigator_affiliation>
    <investigator_full_name>Gary Remington</investigator_full_name>
    <investigator_title>Senior Scientist</investigator_title>
  </responsible_party>
  <keyword>Extended Dosing</keyword>
  <keyword>Alternate day dosing</keyword>
  <keyword>Olanzapine</keyword>
  <keyword>Risperidone</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Schizophrenia</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Olanzapine</mesh_term>
    <mesh_term>Risperidone</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04478838
org study id: 154-2018
nct id: NCT04478838
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
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.
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. 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.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Clinical Deterioration using the "Brief Psychiatric Rating Scale - Expanded"
time frame: 0 and 52 weeks
description: Change in the Brief Psychiatric Rating Scale - total scores from baseline to 52 weeks. The score values for each item on the BPRS range from 1 to 7. The higher the score for each item the worse the outcome. The values for each item on the BPRS are scored as follows:
1- Not Present, 2 - Very Mild, 3- Mild, 4- Moderate, 5 - Moderately Severe, 6- Severe, 7- Very Severe.
measure: Exploratory Outcomes - Symptoms 1 using "The Clinical Global Impression - Schizophrenia Scale"
time frame: 0 and 52 weeks
description: Change in Clinical Global Impression - Schizophrenia (CGI-SCH) severity of illness scores from baseline to 52 weeks. The severity of illness score values for each item on the CGI- SCH range from 1 to 7. The higher the score for each item the worse the outcome.
The severity of illness values are scored as follows:
1- Normal, not ill, 2 -Minimally ill, 3- Mildly ill, 4- Moderately ill, 5 - Markedly ill, 6- Severely ill, 7- Among the most severely ill.
measure: Exploratory Outcomes - Symptoms/Side Effects using "The Clinical Global Impression - Schizophrenia Scale"
time frame: 0 and 52 weeks
description: Change in Clinical Global Impression - Schizophrenia Scale (CGI-SCH) degree of change scores from baseline to 52. The values range from 1-7. The higher the score for each item the worse the outcome. The score value of each item are as follows:
1 - Very much improved, 2 - Much Improved, 3 - Minimally improved, 4 - No Change, 5 - Minimally Worse, 6- Much Worse, 7 - Very Much Worse
measure: Exploratory Outcomes - Symptoms 3 using the "Calgary Depression Scale for Schizophrenia"
time frame: 0 and 52 weeks
description: Change in Calgary Depression Scale (CDS) scores from baseline to 52 weeks. Scores range from 0-3 as follows: 0- Absent, 1- Mild, 2- Moderate, 3 - Severe. The higher the score for each item, the worse the outcome.
measure: Exploratory Outcomes - Symptoms 4 using the "Yale-Brown Obsessive-Compulsive Scale"
time frame: 0 and 52 weeks
description: Change in Yale-Brown Obsessive-Compulsive Scale (YBOCS) scores from baseline to 52 weeks. Scores range from 0-4 with higher scores indicating worsening of outcome.
measure: Exploratory Outcomes - Symptoms 5 using the "Hamilton Anxiety Scale"
time frame: 0 and 52 weeks
description: Change in Hamilton Anxiety Scale (HAM-A) scores from baseline to 52 weeks. Scores on each item range from 0-4 as follows: 0- not present, 1- mild, 2 - moderate, 3- severe, 4 - very severe. Higher scores on each item and total score indicate worsening of anxiety outcome.
measure: Exploratory Outcomes - Side Effects 1 using the "Leibowitz Social Anxiety Scale"
time frame: 0 and 52 weeks
description: Change in Liebowitz Social Anxiety Scale (LSAS) scores from baseline to 52 weeks. For each item, there are 2 scores; 1) score for fear of anxiety and 2) score for avoidance. For the fear of anxiety component of the scale, score ranges from 0-3 as follows: 0- None, 1- Mild, 2- Moderate, 3 - Severe. The scores for the Avoidance component of the scale ranges from 0-3 as follows: 0 - Never, 1- Occasionally, 2 - Often, 3 - Usually. The higher the score the worse the outcome.
measure: Exploratory Outcomes - Side Effects 2 using the "Neurological Evaluation Scale"
time frame: 0 and 52 weeks
description: Change in Neurological Evaluation Scale (NES) scores from baseline to 52 weeks. There are 12 items and scores for each item range from 0-2 with higher scores indicating worsening of outcome. Item 5 does not require a score.
measure: Exploratory Outcomes - Side Effects 3 using the "Glasgow Assessment Side-Effect Scale"
time frame: 0 and 52 weeks
description: Change in Glasgow Assessment Side-Effect Scale (GASS) scores from baseline to 52 weeks. Scores range from 0-3 as follows: 0 -Never, 1- Once, 2 - A few times, 3 - Everyday. The higher the score for each item and higher total indicates a worse side effect outcome.
measure: Exploratory Outcomes - Side Effects 4 using the "Drug Attitude Inventory" Scale
time frame: 0 and 52 weeks
description: Change in Drug Attitude Inventory (DAI) scores from baseline to 52 weeks. Scores are based on 30 true/false statements.There are 15 items that a patient who is fully adherent to their prescribed medication (and so would be expected to have a positive response to medication would answer true and 15 items such a patient would answer as false. Each positive answer is given a score of plus one, and each negative answer is given a score of minus one. The total positive score would indicate a positive response (adherent to medication) whereas a negative total score would indicate a negative response (non adherent to medication).
measure: Exploratory Outcomes - Side Effects 5 using the "Barnes Akathisia Rating Scale"
time frame: 0 and 52 weeks
description: Change in Barnes Akathisia Rating Scale (BARS) scores from baseline to 52 weeks. The total score for the global clinical assessment of akathisia ranges from 0-5 with higher score indicating a worsening of akathisia.
measure: Exploratory Outcomes - Side Effects 6 using the "Simpson Angus Scale"
time frame: 0 and 52 weeks
description: Change in Simpson Angus Scale (SAS) scores from baseline to 52 weeks. There are 13 items in the scale; scores on each item range from 0-4 with higher scores indicating worse extrapyramidal outcome.
measure: Exploratory Outcomes - Side Effects 7 using the "Abnormal Involuntary Movement Scale"
time frame: 0 and 52 weeks
description: Change in Abnormal Involuntary Movement Scale (AIMS) scores from baseline to 52 weeks. There are 13 items in the scale, scores on each item range from 0-4 with higher scores indicating a worse outcome in abnormal movements.
measure: Exploratory Outcomes - Wellbeing using the "Quality of Life and Satisfaction Questionnaire"
time frame: 0 and 52 weeks
description: Change in Quality of Life Scale (QLS) scores from baseline to 52 weeks. The scores for each item range from 0-6. The higher the score, the better the outcome. On several items, there is an additional score of "9" to indicate "not applicable".
measure: Exploratory Outcomes - Wellbeing 2 using the "Quality of Life and Satisfaction Questionnaire - Short Form"
time frame: 0 and 52 weeks
description: Change in Quality of Life and Satisfaction Questionnaire - Short Form (Q-LES-Q-SF) scores from baseline to 52 weeks. Scores range from 0-6 with lower scores indicating a worse outcome.
measure: Exploratory Outcomes - Wellbeing 3 using the "Subject Happiness Scale"
time frame: 0 and 52 weeks
description: .Change in Subjective Happiness Scale (SHS) scores from baseline to 52 weeks. There are 4 items; scores on each item range from 1-7 with higher scores indicating a happier outcome.
measure: Exploratory Outcomes - Function 1 using the "Social and Occupational Function Assessment Scale"
time frame: 0 and 52 weeks
description: Change in : Social and Occupational Function Assessment Scale (SOFAS). scores from baseline to 52 weeks. A total score ranges from 0-100 with higher scores indicating better social and occupational functioning..
measure: Exploratory Outcomes - Function 2 using the "Personal and Social Performance Scale"
time frame: 0 and 52 weeks
description: Change in Personal and Social Performance scale (PSP) scores from baseline to 52 weeks. The ratings are based on four areas (a) socially useful activities, including work and study; b) personal and social relationships; c) self, and d) disturbing and aggressive behaviours. Overall score range from 1-100. The higher the overall rating, the better the outcome. The breakdown of the total Rating score are as follows: scores ranging from 1-30 reflect functioning so poor that intensive support or supervision is needed; ratings from 31-70 reflect manifest disabilities of various degrees; ratings from 71-100 reflect only mild difficulties.
measure: Exploratory Outcomes - Function 3 using the "Recovery Assessment Scale"
time frame: 0 and 52 weeks
description: Change in Recovery Assessment Scale (RAS) scores from baseline to 52 weeks. There are 41 items with scores on each item ranging from 1-5 with higher scores indicating better outcomes.
arm group label: Extended Dosing Group
arm group type: Experimental
description: Participants taking olanzapine or risperidone will be switched to an alternate day dosing schedule.
arm group label: Treatment as Usual group
arm group type: No Intervention
description: Participants will continue to take their olanzapine or risperidone following the same prescribed daily schedule.
intervention type: Drug
intervention name: Risperidone
description: 0.25 mg, 0.5 mg, 1 mg, 2 mg, 3 mg and 4 mg Tablets
arm group label: Extended Dosing Group
other name: Risperdal
intervention type: Drug
intervention name: Olanzapine
description: 2.5 mg, 5 mg, 7.5 mg, 10 mg, 15 mg, 20 mg Tablets
arm group label: Extended Dosing Group
other name: Zyprexa
other name: Apo-Olanzapine
other name: Sandoz-Olanzapine
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Gary J Remington, MD, PhD
role: Principal Investigator
affiliation: Centre for Addiction and Mental Health
last name: Carol Borlido
phone: 416-535-8501
phone ext: 30547
email: carol.borlido@camh.ca
last name: Gary Remington, MD, PhD
phone: 416-535-8501
phone ext: 34750
email: gary.remington@camh.ca
facility: 
status: Recruiting
contact: 
contact backup: 
investigator: 
country: Canada
responsible party type: Principal Investigator
investigator affiliation: Centre for Addiction and Mental Health
investigator full name: Gary Remington
investigator title: Senior Scientist
mesh term: Schizophrenia
mesh term: Olanzapine
mesh term: Risperidone
sharing ipd: No