Predicting Antipsychotic Discontinuation in Psychosis

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to determine whether dopamine synthesis capacity by using [18 fluorine(F)]-DOPA PET for patients with schizophrenia in the maintenance phase can predict treatment discontinuation.

Detailed Description
-----------------
There are two groups: the healthy control group (n=12) and the patient group (n=26). The patient group recruits subjects diagnosed with first episode psychosis which occurred within 2 years and having been treated with antipsychotics for 1 year. Participants will complete clinical scales and undergo PET scans. Subjects in the patient group will receive a reduced intake of antipsychotics by 25% after each week of the four-week period in which they will also undergo PET imaging at the baseline, 7 week, and 8 week marks to detect the correlation between the capacity of presynaptic dopamine and relapse in the patients discontinuing treatment.

Official Title
-----------------
Predicting Successful Antipsychotic Discontinuation in the First Episode Psychosis by Using Positron Emission Tomography(PET) withPositron Emission Tomography With 3,4-dihydroxy-6-18-fluoro-l-phenylalanine ([18 Fluorine(F)]DOPA)

Conditions
-----------------
Schizophrenia

Intervention / Treatment
-----------------
* Device: PET
* Behavioral: clinical scale


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: 1. Patient group Patients who met DSM-IV criteria for schizophrenia, schizoaffective disorder, and schizophreniform disorder patients diagnosed with first episode psychosis which occurred within 2 years and having been treated with antipsychotics for at least 1 year. Patients who have maintained in the stable state for 3 months without medication change at the baseline. 2. Healthy control group Healthy controls has no Axis I disorder and do not report any past event of neurological or psychiatric illness assessed by the Structured Clinical Interview for DSM Disorders Exclusion Criteria: Participants should not have any neurological illness such as head trauma, seizure and meningitis. Participants should not be diagnosed as Mental retardation(IQ<70) Participants should not have severe personality disorder, substance abuse or dependence (except for nicotine abuse and dependence) and severe medical conditions.

Ages Eligible for Study
-----------------
Minimum Age: 19 Years
Maximum Age: 45 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: patient group<br>The patient group recruits subjects diagnosed with first episode psychosis which occurred within 2 years and having been treated with antipsychotics for 1 year. Subjects in the patient group will receive a reduced intake of antipsychotics by 25% after each week of the four-week period in which they will also undergo PET imaging at the baseline, 7 week, and 8 week marks to detect the correlation between the capacity. And patient group should complete clinical scales at 0, 2, 4, 6, and 8 week. | Device: PET<br>* Subjects in the patient group will receive a reduced intake of antipsychotics by 25% after each week of the four-week period in which they and healthy controls will also undergo PET imaging at the baseline, 7 week, and 8 week marks to detect the correlation between the capacity of presynaptic dopamine and relapse in the patients discontinuing treatment.<br>Behavioral: clinical scale<br>* Healthy controls should complete clinical scales at baseline. Patient group should complete clinical scales at 0, 2, 4, 6, and 8 week.<br>|
| Other: healthy control group<br>Screening tests for healthy volunteers included physical examination, vital signs, laboratory will test (hematology, blood chemistry, and urinalysis), and a 12-lead electrocardiograms. A psychiatric interview with the Structured Clinical Interview for text revision of the Diagnostic and Statistical Manual of Mental Disorders -IV(DSM-IV-TR) Axis I disorders, Research Version, Nonpatient Edition (SCID-I/NP) (First et al. 2002) will be conducted. Subjects with any medically significant abnormality on investigations and/or psychiatric disease will be excluded. Also, healthy control group will take a PET scan at 0, 2, 4, 6, and 8 week and clinical scales at baseline. | Device: PET<br>* Subjects in the patient group will receive a reduced intake of antipsychotics by 25% after each week of the four-week period in which they and healthy controls will also undergo PET imaging at the baseline, 7 week, and 8 week marks to detect the correlation between the capacity of presynaptic dopamine and relapse in the patients discontinuing treatment.<br>Behavioral: clinical scale<br>* Healthy controls should complete clinical scales at baseline. Patient group should complete clinical scales at 0, 2, 4, 6, and 8 week.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ki(cer) of 3,4-dihydroxy-6-18-fluoro-l-phenylalanine ([18 fluorine(F)]DOPA PET) | Subjects in the patient group will receive a reduced intake of antipsychotics by 25% after each week of the six-week period in which they will also undergo PET imaging at the baseline and six-week marks to detect the correlation between the capacity of presynaptic dopamine and relapse in the patients discontinuing treatment. | Change from Baseline Ki(cer) of [18 fluorine(F)]DOPA PET at 7 weeks and at 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Positive and Negative Syndrome Scale(PANSS)Scale | Psychotic symptoms will be assessed by using PANSS at 0, 2, 4, 6, and 8 wk | at 0, 2, 4, 6, and 8 wk | 
| Brief Psychiatric Rating Scale(BPRS) | Psychotic symptoms will be assessed by using BPRS at 0, 2, 4, 6, and 8 wk | at 0, 2, 4, 6, and 8 wk | 
| Young Mania Rating Scale(YMRS) | Mood symptoms will be assessed by using YMRS at 0, 2, 4, 6 and 8 wk | at 0, 2, 4, 6 and 8 wk | 
| Hamilton Depression Rating Scale(HAM-D) | Mood symptoms will be assessed by using HAM-D at 0, 2, 4, 6 and 8 wk | at 0, 2, 4, 6 and 8 wk | 
| Columbia Suicide Severity Rating Scale(C-SSR) | Suicide risk will be assessed by using C-SSR at 0, 2, 4, 6, and 8 wk | at 0, 2, 4, 6, and 8 wk | 
| Quality of Life Scale(QoL) | QoL will be assessed at 0 , 4 and 8 wk | at 0 , 4 and 8 wk | 
| Adverse effects | Adverse effects will be assessed by using side effect rating scale at 0 and 4 wk | at 0 and 4 wk | 
| Kv-Subjective Well-Being Under Neuroleptics Scale(SWN)-K | Dysphoria will be assessed by using Kv-SWN-K at 0, 4 and 8 wk | at 0, 4 and 8 wk | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
dopamine receptor occupancy, antipsychotics, positron emission tomography