Research Into Antipsychotic Discontinuation and Reduction Trial

Study Overview
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Brief Summary
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Psychosis and schizophrenia are common and costly mental health problems. Psychosis is the name given to a group of mental conditions in which cause people to perceive or interpret things differently from those around them. One of the most common causes of psychosis is schizophrenia, a condition that causes a range of psychological symptoms, including hallucinations (hearing and/or seeing things) and delusions (believing something that is not true). One of the main treatment options for psychosis and schizophrenia is long-term treatment with antipsychotic medication, but many patients still find life difficult. Antipsychotic drugs can also have dangerous and unpleasant side effects. Finding alternatives to long-term drug treatment is a priority for patients and services. This study is testing the effects of gradually reducing antipsychotic medication in people with schizophrenia, psychosis or similar conditions in order to see if it can help improve day-to-day functioning and how it affects their chance of suffering a relapse (worsening of their condition).

Detailed Description
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The RADAR trial is a randomised controlled trial that will compare a flexible and gradual strategy of antipsychotic reduction and possible discontinuation with maintenance antipsychotic treatment in people with schizophrenia or who have recurrent psychotic episodes. In the reduction group, a guideline reduction schedule will be devised by the research team for each participant taking into account starting dose and number of antipsychotics prescribed. This may be adjusted by treating clinicians in discussion with participants. Antipsychotics will be discontinued in cases where reduction progresses well. The reduction schedule will be flexible, and will include guidance on monitoring and treating symptoms and signs of early relapse. Participants will be individually randomised to the two treatment strategies, which will be administered by treating clinicians. They will be followed up for two years. The primary outcome is social functioning, and secondary outcomes include relapse, symptoms, side effects, employment and medication adherence.

Official Title
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Research Into Antipsychotic Discontinuation and Reduction (RADAR): A Randomised Controlled Trial

Conditions
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Schizophrenia, Schizoaffective Disorder, Delusional Disorder, Schizophreniform Disorders

Intervention / Treatment
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* Drug: Antipsychotic Reduction
* Drug: Antipsychotic Maintenance


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged over 18 years A clinical and/or ICD10 diagnosis of schizophrenia, schizoaffective disorder, delusional disorder or other non-affective psychosis More than one previous episode of relapse or psychotic exacerbation, or a single episode lasting more than one year Taking antipsychotic medication Exclusion Criteria: Participant lacks capacity to consent to the trial Participant has insufficient command of spoken English to understand trial procedures Participant subject to section 37/41 of the Mental Health Act (MHA) or a Community Treatment Order (CTO) that includes a requirement to take antipsychotic medication. Clinician considers there will be a serious risk of harm to self or others Participant has been admitted to hospital or had treatment from the Home Treatment or Crisis Team within the last month Females who have a confirmed pregnancy Females who are breast-feeding Involvement in another investigational medicinal product (IMP) trial No contraindications to continuing on antipsychotic medication

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Open, parallel group, multi-centre randomised controlled trial.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Antipsychotic Maintenance<br>Participants continue to receive antipsychotic treatment at the original dose for the 24 month duration of the trial. Increases or minor adjustments to antipsychotic medication are permitted. | Drug: Antipsychotic Maintenance<br>* Participants continue to receive antipsychotic treatment at the original dose for the 24 month duration of the trial. Increases or minor adjustments to antipsychotic medication are permitted.<br>|
| Experimental: Antipsychotic Reduction<br>Antipsychotic medication is gradually reduced and discontinued if possible. A flexible individualised antipsychotic reduction schedule is devised for each patient by the research team, based on the participant's initial antipsychotic regime. Antipsychotic dose is reduced incrementally every two months, with flexibility to speed up or slow down the schedule in discussion with the patient. The antipsychotic reduction extends over a period of between six to 12 months, although this may be extended according to individual circumstances. | Drug: Antipsychotic Reduction<br>* Antipsychotic medication is gradually reduced and discontinued if possible. A flexible individualised antipsychotic reduction schedule is devised for each patient by the research team, based on the participant's initial antipsychotic regime. Antipsychotic dose is reduced incrementally every two months, with flexibility to speed up or slow down the schedule in discussion with the patient. The antipsychotic reduction extends over a period of between six to 12 months, although this may be extended according to individual circumstances.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Social Functioning Scale (Assessing change over time) | Evaluates how the patient functions in daily living and social skills | Baseline, 6 months, 12 months, 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Severe relapse | Severe relapse is defined as admission to hospital for a relapse of a psychotic condition. | Duration of the trial follow-up (24 months) | 
| Positive and Negative Syndrome Scale (PANSS) Assessing change over time | Clinical assessment of current symptomology. Measure refers to prevalence of psychotic symptoms ranging from absent to extreme. | Baseline, 6 months, 12 months, 24 months | 
| Modified Glasgow Antipsychotics Side-Effects Scale (GASS) Assessing change over time | Self-report measure of physical and mental side effects patient has experienced recently. Scale refers to prevalence of side effects from antipsychotic medication in the last week. | Baseline, 6 months, 12 months, 24 months | 
| Manchester Short Assessment of Quality of Life (MANSA) Assessing change over time | Assessment of quality of life. | Baseline, 6 months, 12 months, 24 months | 
| Digit Span (forwards and backwards) Assessing change over time | Neuropsychological assessment of short-term memory and attention | Baseline,12 months, 24 months | 
| Digit Symbol Coding (Assessing change over time) | A neuropsychological assessment of motor skill and attention | Baseline,12 months, 24 months | 
| Rey Auditory Verbal Learning (Assessing change over time) | Neuropsychological assessment of short-term memory and learning | Baseline,12 months, 24 months | 
| Trail Making Test (Assessing change over time) | Neuropsychological assessment of motor skills | Baseline,12 months, 24 months | 
| Verbal Fluency (Assessing change over time) | Neuropsychological assessment of language and communication skills | Baseline,12 months, 24 months | 
| Demographic Information | Demographic data about the participant | Baseline | 
| Client Service Receipt Inventory (CSRI) Assessing change over time | Economic measure of health service use including frequency services are used (inc. mental health, physical health, criminal justice, council activities) and medication currently used (inc. measuring dosage, frequency, medication name, and how long its been taken for) | Baseline, 12 months, 24 months | 
| Schedule for Economic Data from Patient Records | Health information from patient notes to inform economic analysis | Baseline, 12 months, 24 months | 
| Questionnaire about the Process of Recovery (QPR) Assessing change over time | Evaluates how participants view their recovery | Baseline, 6 months, 12 months, 24 months | 
| Work Productivity and Activity Questionnaire (WPAI) Assessing change over time | Measure of the effect of health problems on occupational functioning (i.e. ability to work and perform normal daily activities) | Baseline, 6 months, 12 months, 24 months | 
| Relapse Questionnaire (Assessing change over time) | Self-report measure of any recent experience of what the patient or their close ones would describe as a relapse (severe or non-severe). Developed for this trial to identify instances of severe and non-severe relapse. | 6 months, 12 months, 24 months | 
| Medication Adherence Rating Scale (MARS-5) Assessing change over time | Self-report measure of how participant is currently using antipsychotic medication (medication adherence) | Baseline, 6 months, 12 months, 24 months | 
| Client Satisfaction Questionnaire (CSQ 8) Assessing change over time | Patient satisfaction with mental health services. | Baseline, 6 months, 12 months, 24 months | 
| EQ-5D-5L (Euroqol five levels- Assessing change over time) | Measure of health status | Baseline, 6 months, 12 months, 24 months | 
| ICECAP-A (ICEpop CAPability measure for Adults) Assessing change over time | Measure of quality of life | Baseline, 6 months, 12 months, 24 months | 
| Arizona Sexual Experiences Scale (ASEX) Assessing change over time | Evaluates sexual functioning | Baseline, 6 months, 12 months, 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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antipsychotics, schizophrenia, reduction