Early Predictors of Poor Treatment Response in Patients With Schizophrenia Treated With Atypical Antipsychotics

NCT ID: NCT03730857

Last Updated: 2019-02-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 111 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-01-31
• Study Completion Date: 2008-12-31

Brief Summary

Background: The aims of this study were to explore the relationship between early reduction in psychotic symptoms and the ultimate response in patients with schizophrenia treated by atypical antipsychotics, and to determine the best time to switch or maitain the regimen. PI also explore the possible predictors for the clinical response.

Methods: One hundred eleven inpatients with acutely exacerbated schizophrenia were randomized to give optimal therapy of olanzapine, risperidone, and paliperidone in one-week run-in period and 12 weeks' intervention. All participants were assessed using Positive and Negative Syndrome Scale (PANSS). Early Response, defined as reduction of 25% in PANSS score, was examined at weeks 1, 2, 3, 4 and 8, and these ratings were used to predict ultimate response (25% PANSS reduction) at week 12. PI hypothesized that early treatment response at Week 1 or 2 could predict Week 12's treatment outcome.

Detailed Description

Study Design: This study recruited hospitalized adult patients who had a relapse of schizophrenia. All participants had received antipsychotic treatment for a period of time previously. They have to meet the diagnostic criteria for schizophrenia according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV). One hundred and twenty adult inpatients were recruited and were randomly assigned to receive olanzapine (n=60), risperidone (n=30) and paliperidone (n=30) in an allocation ratio of 2:1:1. The participants were allowed to change the dosage of antipsychotics and their hospitalization status according to the judgement of in-charged physicians during the study period.

The study was approved by the Institutional Review Board and written informed consents were obtained either directly from the patients or from their legal guardians after the study had been explained. The inclusion criteria for this study were: (1) age 18 to 65 years, (2) no major systemic illnesses based on physical examinations and laboratory test results, and (3) baseline PANSS total score≧60. The exclusion criteria were as follows: (1) participants not taking any antipsychotics in the previous one month, (2) participants were pregnant and lactating women, and (3) history of clozapine treatment in the previous 3 months, and (4) patients receiving long-acting antipsychotic injections in the preceding 6 months of enrollment.

This study was conducted by a 12-week, open-label and naturalistic randomized design. A tri-therapy (olanzapine, risperidone, and paliperidone) completely randomized design was adopted for this study, which involved three homogeneous groups of patients with a run-in period of 3 months. The patients were required to have discontinued all prior use of antipsychotics for a period of at least 7 days before their entry into the study. During wash-out period, administration of either oral benzodiazpines, hypnotics or injection of lorazepam to control anxiety, insomnia and aggression were allowed. After the wash-out period, the patients received treatment with an atypical antipsychotic drug, olanzapine, risperidone or paliperidone for 3 months.

The Positive and Negative Syndrome Scale (PANSS) rating scale was used to evaluate the changes of psychiatric symptoms in each time point. The subject patients were interviewed for the PANSS by senior psychiatrists. The raters in the present study had worked mainly on inpatient treatment of severe schizophrenic patients, and were well acquainted with symptoms of schizophrenia. Prior to the present study, all participating psychiatrists had received adequate training through the manual and they had had clinical experience in the PANSS rating before the study. At each time point if the scores of PANSS showed the patient's symptoms had worsened, the dosage would be adjusted based on the clinical judgment of in-charged senior psychiatrist. However, if the scores of PANSS were improved, the dosage was maintained. The recommended dose for the three groups were as follows: 10 to 20 mg daily for olanzapine, 4 to 6 mg daily for risperidone, and 6 to 12 mg daily for paliperidone. Throughout the study period, the paticipants were allowed to continuously use some concomitant medication, including lorazepam (up to 6 mg/day) for insomnia or agitation and biperiden (up to 6 mg/day) for treatment of extrapyramidal side effects. No other psychotropic agents were administered during the 12-week study.

Conditions

Schizophrenia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: FACTORIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

olanzapine

olanzapine has a dose of 10 to 20 mg daily for 12 weeks

Group Type: ACTIVE_COMPARATOR

Olanzapine

Intervention Type: DRUG

olanzapine tablet

risperidone

risperidone at a dose of 4 to 6 mg daily for 12 weeks

Group Type: ACTIVE_COMPARATOR

risperidone

Intervention Type: DRUG

risperidone tablet

paliperidone

paliperidone at a dose of 6 to 12 mg daily for 12 weeks.

Group Type: ACTIVE_COMPARATOR

Paliperidone

Intervention Type: DRUG

paliperidone tablet

Interventions

Olanzapine

olanzapine tablet

Intervention Type: DRUG

risperidone

risperidone tablet

Intervention Type: DRUG

Paliperidone

paliperidone tablet

Intervention Type: DRUG

Other Intervention Names

second-generation antipsychotics; second-generation antipsychotics; second-generationantipsychotics

Eligibility Criteria

Inclusion Criteria

• (1) age 18 to 65 years,
• (2) no major systemic illnesses based on physical examinations and laboratory test results,
• (3) baseline PANSS total score≧60

Exclusion Criteria

• (1) participants not taking any antipsychotics in the previous one month,
• (2) participants were pregnant and lactating women,
• (3) history of clozapine treatment in the previous 3 months,
• (4) patients receiving long-acting antipsychotic injections in the preceding 6 months of enrollment

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Calo Psychiatric Center

OTHER

Sponsor Role: lead

Responsible Party

For-Wey Lung

Superintendent and Attending physician

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

For-Wey Lung, MD, ScD

Role: PRINCIPAL_INVESTIGATOR

Calo Psychiatric Center

References

Chen YL, Chen KP, Chiu CC, Tai MH, Lung FW. Early predictors of poor treatment response in patients with schizophrenia treated with atypical antipsychotics. BMC Psychiatry. 2018 Dec 4;18(1):376. doi: 10.1186/s12888-018-1950-1.

Reference Type: DERIVED

PMID: 30509308 (View on PubMed)

Other Identifiers

T1-02

Identifier Type: -

Identifier Source: org_study_id