Treatment Strategy for Refractory Schizophrenia: Drug Interaction Between Clozapine and Fluvoxamine
Information source: Taipei Medical University Hospital
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Schizophrenia
Intervention: clozapine plus fluvoxamine (Drug); clozapine plus placebo (Drug)
Phase: Phase 4
Status: Completed
Sponsored by: Taipei Medical University Hospital Official(s) and/or principal investigator(s): Mong-Liang Lu, Principal Investigator, Affiliation: Taipei Medical University-Wan Fang Hospital
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.
Clinical Details
Official title: Treatment Strategy for Refractory Schizophrenia: Drug Interaction Between Clozapine and Fluvoxamine
Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor), Primary Purpose: Treatment
Primary outcome: the changes in the psychopathology during the trialthe changes in the metabolic syndrome parameters during the trial
Secondary outcome: the changes in the plasma drug levelsThe changes in insulin levels The changes in the depression severity The changes in the adipokine levels
Detailed description:
Background Schizophrenia is one of the most severe mental illnesses. The prevalence of
schizophrenia has been variously reported as ranging from 1 to 1. 5 percent. More than 50% of
patients can be described as having a poor outcome, with repeated hospitalizations,
exacerbations of symptoms, episodes of major mood disorders, and suicide attempts.
Schizophrenia is costly in medical care, treatment and rehabilitation, and reduced or lost
productivity. Therefore, the development of effective treatment for schizophrenic patients
is an important issue.
The classical antipsychotic drugs are the dopamine receptor antagonists, which are effective
in the treatment of schizophrenia, particularly of the positive symptoms. Even with
treatment of typical antipsychotics, about 50% of schizophrenic patients lead severely
debilitated lives. Second, the classical antipsychotic drugs are associated with annoying
and serious adverse effects. 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 mean plasma clozapine levels obtained by clozapine 100 mg/day plus fluvoxamine
50 mg/day is close to that produced by 300-mg/day clozapine monotherapy in one of our
previous studies. 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.
Methods This study is a three-year proposal. Sixty treatment-resistant schizophrenic
inpatients will participate in this project. The subjects will be randomized to one of two
parallel groups: clozapine monotherapy and clozapine plus fluvoxamine treatment. The
double-blind active treatment will consist of two periods.
The measures of clinical efficacy will be the Positive And Negative Syndrome Scale, Clinical
Global Impression, and Nurses'Observation Scale for Inpatient Evaluation. The measures of
side effects will be the Extrapyramidal Symptom Rating Scale and the UKU Side Effect Rating
Scale. Fasting serum samples are collected to determine the lipid profile (total
cholesterol, triglycerides, HDL, and LDL), glucose level, and insulin level. Plasma levels
of clozapine, norclozapine, and clozapine N-oxide will be determined by high performance
liquid chromatography with ultraviolet detection.
The following results are expected:
1. In treatment-resistant schizophrenic patients, global antipsychotic effect of clozapine
plus fluvoxamine treatment is superior to clozapine monotherapy.
2. Clozapine plus fluvoxamine treatment has less adverse effects than clozapine
monotherapy.
3. The effect of clozapine plus fluvoxamine treatment on body weight and metabolic
disturbances is superior to clozapine monotherapy.
4. Steady-state plasma levels of clozapine and its metabolites account for a proportion of
variance of clinical effects.
Eligibility
Minimum age: 18 Years.
Maximum age: 60 Years.
Gender(s): Both.
Criteria:
Inclusion Criteria:
1. Inpatients meet the DSM-IV criteria for schizophrenia.
2. 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.
3. Age 18-60 years.
4. Males or females.
5. Total PANSS score >60
6. Good physical health determined by complete physical examination, laboratory tests,
and EKG.
7. Capacity and willingness to give written informed consent.
Exclusion Criteria:
1. History of illicit substance abuse or dependence
2. History of clozapine intolerance (such as clinically significant leukopenia or
agranulocytosis).
3. Patients with WBC count less than 3500/mm3 or ANC count less than 2000/mm3will not be
included.
4. Any depot neuroleptics within 30 days before the day of randomization.
5. Epilepsy, active hepatitis, HIV positivity, or current myeloproliferative disorder.
Other medical illnesses may necessitate subjects' exclusion after evaluation of
individual cases by the principal investigator and other staffs. Clinical judgment
will be used.
Locations and Contacts
Taipei Medical University-Wan Fang Hospital, Taipei 116, Taiwan
Additional Information
Starting date: January 2008
Last updated: July 21, 2011
|