Chinese First Episode Schizophrenia's Optimal Dynamic Antipsychotic Treatment Regime

Study Overview
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Brief Summary
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This project is mainly to clarify the optimal treatment plan and the treatment recommendation sequence of different drugs in Chinese first-episode schizophrenia patients,to identify the optimized sequential treatment regimen for the treatment of resistance patients and provide new evidence for the revision of the guidelines for the treatment of schizophrenia.

Detailed Description
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This project will be a large sample, multi-center clinical trials for first episode schizophrenia. We plan to get a clear initial regimen and the drug recommendation in the treatment of first episode schizophrenia in China, based on the efficacy, adverse effect and pharmacoeconomics evaluation for the most widely used antipsychotic drugs (amisulpride, risperidone, olanzapine, aripiprazole ) and paliperidone injection. We will carry out sequential treatment trials in first-episode treatment resistant patients (Phase 2: Randomized controlled trials of other antipsychotic drugs that are not used in Phase 1 and paliperidone injection; Phase 3: Clozapine monotherapy, oral administration of other drugs or long-acting injection in treatment; Phase 4: Clozapine combination therapy or any combination of two other antipsychotics), so that we could get a better sequential treatment protocol based on the therapeutic outcome. The current project has great clinical significance.

Official Title
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Estimating the Optimal Dynamic Antipsychotic Treatment Regime: Sequential Multiple-assignment Randomized Clinical Antipsychotic Trials in Chinese Patients With First-episode Psychosis.

Conditions
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Schizophrenia

Intervention / Treatment
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* Drug: Olanzapine
* Drug: Risperidone
* Drug: Aripiprazole
* Drug: Amisulpride
* Drug: Paliperidone long-acting injection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Meet the diagnostic criteria of Diagnostic and Statistical Manual Diploma in Social Medicine(DSM-V) schizophrenia or schizophreniform psychosis Patient interview using the MINI-International Neuropsychiatric Interview(MINI 7.0) 18 to 40 years of age First episode, disease course less than 3 years Antipsychotic naïve, or the time of taking the same type of antipsychotic <2 weeks (2 weeks is a time criterion to determine the efficacy in lots of studies), and cumulative antipsychotic drug exposure time <6 weeks Informed consent. In addition, the severity of psychiatric symptoms is moderate or above, the specific criteria are: All patients have a score ≥4 on at least one Positive and Negative Syndrome Scale (PANSS; 17) psychosis item (delusions, conceptual disorganization, hallucinatory behavior, grandiosity, or suspiciousness/persecution) All patients have a score ≥4 (moderately ill) on the severity item of the Clinical Global Impression scale (CGI; 19) at the point of maximum severity of illness to date Exclusion Criteria: organic disease severe physical illness psychoactive substance dependence mental retardation pregnancy or breast-feeding patients extreme agitation, stupor, negative suicide other non-cooperation or risk patients

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 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: Sequential Assignment
Interventional Model Description: Real-World Study Based on SMART Design: Subjects were arranged according to patient's wishes and randomized allocation. Next phase of treatment was determined based on the patient's response (efficacy and adverse reactions). We could not achieve double blind designed protocol; however, assessor's blindness could be achieved in the design.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Olanzapine<br>dosage form:po dosage:5-20mg frequency:qn duration:If the drug is effective, it can be taken for a long time. If the drug is ineffective or the side effect is too difficult to tolerate, the drug should be changed according to the treatment stage. | Drug: Olanzapine<br>* Commonly used oral antipsychotics intervention therapy.<br>|
| Experimental: Risperidone<br>dosage form:po dosage:4-6mg frequency:2 doses duration:If the drug is effective, it can be taken for a long time. If the drug is ineffective or the side effect is too difficult to tolerate, the drug should be changed according to the treatment stage. | Drug: Risperidone<br>* Commonly used oral antipsychotics intervention therapy.<br>|
| Experimental: Amisulpride<br>dosage form:po dosage:0.4-1.2g frequency:2 doses duration:If the drug is effective, it can be taken for a long time. If the drug is ineffective or the side effect is too difficult to tolerate, the drug should be changed according to the treatment stage. | Drug: Aripiprazole<br>* Commonly used oral antipsychotics intervention therapy.<br>|
| Experimental: Aripiprazole<br>dosage form:po dosage:15-30mg frequency:qd duration:If the drug is effective, it can be taken for a long time. If the drug is ineffective or the side effect is too difficult to tolerate, the drug should be changed according to the treatment stage. | Drug: Amisulpride<br>* Commonly used oral antipsychotics intervention therapy.<br>|
| Experimental: Paliperidone long-acting injection<br>dosage form:im dosage:75-150mg frequency:once a month duration:If the drug is effective, it can be taken for a long time. If the drug is ineffective or the side effect is too difficult to tolerate, the drug should be changed according to the treatment stage. | Drug: Paliperidone long-acting injection<br>* long-acting injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in Positive and Negative Syndrome Scale [PANSS] | Reduction to the PANSS total score≥50% | baseline,2 months,4 months and 6 months and 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in Psychiatric Symptom severity scale (CRDPSS) | Psychiatric Symptom severity scale (CRDPSS) | baseline,2 months,4 months and 6 months and 12 months | 
| Change from baseline in the Cost inventory | Cost inventory | baseline,2 months,4 months and 6 months and 12 months | 
| Change from baseline in overall clinical impression Scale (CGI) | overall clinical impression Scale (CGI) | baseline,2 months,4 months and 6 months and 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Schizophrenia; Antipsychotics；Cost-Effectiveness Analyses