Early Predictors of Poor Treatment Response in Patients With Schizophrenia Treated With Atypical Antipsychotics
Condition: Schizophrenia
MeSH terms: Schizophrenia
Study type: Interventional
Phase: Phase 1

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.
    

Intervention name(s): Olanzapine; risperidone; Paliperidone
Intervention type(s): Drug; Drug; Drug
Intervention description(s): olanzapine tablet; risperidone tablet; paliperidone tablet
Other intervention name(s): second-generation antipsychotics; second-generation antipsychotics; second-generationantipsychotics
Intervention MeSH terms: Olanzapine; Risperidone; Paliperidone Palmitate; Antipsychotic Agents
Allocation: Randomized
Intervention model: Factorial Assignment
Intervention model description: 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.
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: schizophrenia; PANSS; positive predictive value; negative predictive value