Treatment Strategy for Refractory Schizophrenia: Drug Interaction Between Clozapine and Fluvoxamine

NCT01401491 | Completed Phase 4

• 1 other identifier: 95019
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

Brief Summary

Clozapine has been virtually the only psychopharmacological choice in patients with schizophrenia who either did not response to typical neuroleptics or experienced severe extrapyramidal side effects and consequently did not tolerate this medication. There are patients who do not respond to clozapine, and the need to treat these severely ill patients frequently compels clinicians to adopt therapeutic innovations that lack a sound empirical basis. One strategy is the combination of various other somatic treatments with clozapine. Recently, the investigators conduct a preliminary open trial to evaluate the safety and efficacy of fluvoxamine coadministration with clozapine in refractory schizophrenic patients. The combined treatment is well tolerated, and clinical improvement is observed in our patients. And the concomitant fluvoxamine could attenuate the clozapine-induced weight gain and metabolic disturbance. However, the effects of fluvoxamine on the safety and therapeutic efficacy of clozapine need to be further clarified in double-blind study.

Conditions

Schizophrenia

Keywords

schizophrenia; clozapine; fluvoxamine; metabolic syndrome

Outcome Measures

Primary Outcomes (2)

• the changes in the psychopathology during the trial

  The changes in the scores of psychopathology assessment (the Positive and Negative Syndrome Scale, PANSS)

  every 2 weeks

• the changes in the metabolic syndrome parameters during the trial

  The changes in the metabolic syndrome parameters

  every 2 weeks

Secondary Outcomes (4)

• the changes in the plasma drug levels

  every 2 weeks

• The changes in insulin levels

  every 2 weeks

• The changes in the depression severity

  every 2 weeks

• The changes in the adipokine levels

  every 2 weeks

Study Arms (2)

clozapine + fluvoxamine

ACTIVE COMPARATOR

Drug: clozapine plus fluvoxamine

clozapine + placebo

PLACEBO COMPARATOR

Drug: clozapine plus placebo

Interventions

clozapine plus fluvoxamine DRUG

clozapine 100 mg/day plus fluvoxamine 50 mg/day

clozapine + fluvoxamine

clozapine plus placebo DRUG

clozapine 300 mg/day plus placebo

clozapine + placebo

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Inpatients meet the DSM-IV criteria for schizophrenia.
• Treatment refractoriness: Failed to respond to at least two typical neuroleptics at dosage equivalent to or greater than 1000 mg/day of chlorpromazine for a period of at least six weeks.
• Age 18-60 years.
• Males or females.
• Total PANSS score \>60
• Good physical health determined by complete physical examination, laboratory tests, and EKG.
• Capacity and willingness to give written informed consent.

You may not qualify if:

• History of illicit substance abuse or dependence
• History of clozapine intolerance (such as clinically significant leukopenia or agranulocytosis).
• Patients with WBC count less than 3500/mm3 or ANC count less than 2000/mm3will not be included.
• Any depot neuroleptics within 30 days before the day of randomization.

Sponsors & Collaborators

• Taipei Medical University Hospital: lead
• National Health Research Institutes, Taiwan: collaborator

Study Sites (1)

Taipei Medical University-Wan Fang Hospital

Taipei, 116, Taiwan

Location

Related Publications (1)

• Lu ML, Chen TT, Kuo PH, Hsu CC, Chen CH. Effects of adjunctive fluvoxamine on metabolic parameters and psychopathology in clozapine-treated patients with schizophrenia: A 12-week, randomized, double-blind, placebo-controlled study. Schizophr Res. 2018 Mar;193:126-133. doi: 10.1016/j.schres.2017.06.030. Epub 2017 Jul 6.

  PMID: 28688742 DERIVED

MeSH Terms

Conditions

Schizophrenia; Metabolic Syndrome

Interventions

Clozapine; Fluvoxamine

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders; Insulin Resistance; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Dibenzazepines; Heterocyclic Compounds, 3-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Oximes; Hydroxylamines; Amines; Organic Chemicals

Study Officials

• Mong-Liang Lu

  Taipei Medical University-Wan Fang Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: May 19, 2011
• First Posted: July 25, 2011
• Study Start: January 1, 2008
• Primary Completion: December 1, 2010
• Study Completion: December 1, 2010
• Last Updated: July 25, 2011

Record last verified: 2011-07

Locations

TW (1)