Schizophrenia Mental and Behavioural Disorders Schizophrenia
Conditions
Interventions
This study is designed as an open multicentre study to be performed in the Departments of Psychiatry and Psychotherapy, Klinikum Fulda gAG and the Philipps-University of Marburg, Germany. Recruitment
Sponsors
Klinikum Fulda gAG (Germany)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Diagnosis of schizophrenia by Diagnostic and Statistical Manual of Mental Disorders - Fourth Edition (DSM-IV) 1.1. Paranoid type (295.30) 1.2. Catatonic type (295.20) 1.3. Disorganised type (295.10) 1.4. Undifferentiated type (295.90) 1.5. Residual type (295.60) 2. Females and males aged 18 - 55 years 3. Clinical indication for a new treatment with antipsychotics (in case of an acute phase) or an adaptation or change of antipsychotic medication (due to an instable course) 4. Positive and Negative Syndrome Scale (PANSS) score at entry greater than 60 5. Female patients of childbearing potential must be using a reliable method of contraception and have a negative urine human chorionic gonadotropin (HCG) test at enrolment 6. Written informed consent 7. Capability to understand and comply with the requirements of the study 8. Patients without any medication affecting (serotonergic, dopaminergic and noradrenergic neurotransmission) 9. Patients with antipsychotic and/or antidepressive pre-treatment can be enrolled after a wash out period of 7 days. In case of fluoxetine at least 4 weeks.
Exclusion criteria
Exclusion criteria: 1. Any DSM-IV Axis I disorder not defined in the inclusion criteria 2. Predominantly organic psychosis 3. Any medical disease which will be related to psychopathology of the patient or will interfere with treatment requirements 4. Substance or alcohol dependence at enrolment (except dependence in full remission, and except for caffeine or nicotine dependence), as defined by DSM-IV criteria 5. Opiates, amphetamine, barbiturate, cocaine, cannabis, or hallucinogen abuse by DSM-IV criteria within 4 weeks prior to enrolment 6. Treatment with drugs affecting (serotonergic, dopaminergic and noradrenergic neurotransmission), especially neuroleptics, antidepressants, sedatives 7. Patients who had suffered from colzapine-induced agranulocytosis, or who had been treated with clozapine during two months prior to enrolment 8. Pregnancy or lactation 9. Patients who, in the opinion of the investigator, pose an imminent risk of suicide or a danger to self or others 10. Known intolerance or lack of response to quetiapine fumarate, as judged by the investigator 11. Use of any of the following cytochrome P450 3A4 inhibitors in the 14 days preceding enrolment including but not limited to: ketoconazole, itraconazole, fluconazole, erythromycin, clarithromycin, troleandomycin, indinavir, nelfinavir, ritonavir, fluvoxamine and saquinavir 12. Use of any of the following cytochrome P450 inducers in the 14 days preceding enrolment including but not limited to: phenytoin, carbamazepine, barbiturates, rifampin, St John's Wort, and glucocorticoids 13. Administration of a depot antipsychotic injection within one dosing interval (for the depot) before randomisation 14. Medical conditions that would affect absorption, distribution, metabolism, or excretion of study treatment 15. Unstable or inadequately treated medical illness (e.g. diabetes, angina pectoris, hypertension) as judged by the investigator 16. Involvement in the planning and conduct of the study 17. Previous enrolment or randomisation of treatment in the present study. 18. Participation in another drug trial within 4 weeks prior enrolment into this study or longer in accordance with local requirements
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Level of HVA at baseline and after quetiapine treatment (4 weeks) in CSF | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Pharmacokinetics and pharmacogenetics: Atypical antipsychotic drugs are generally biotransformed to metabolites that have a different pharmacological and pharmacokinetic profile from that of the parent compound. Consequently, the hypothesis that metabolic and pharmacokinetic properties of a drug and its metabolites play an important role in their overall pharmacological activity is plausible and needs to be explored for quetiapine. Preliminary exploratory information will be obtained on: 1.1. The relative concentrations of quetiapine in cerebrospinal fluid (CSF) versus plasma, and on the plasma/CSF ratio-clinical effectiveness relationship in patients with schizophrenia, taking into account the phenotype/genotype of MDR1-polymorphism. To date no published data are available on this issue. 1.2. The role of the MDR1-polymorphism on the concentrations of quetiapine and 5-HIAA and HVA in CSF, and on the possible existence of a transport of quetiapine through the blood brain barrier The hypothesis is that the relative concentrations of quetiapine in cerebrospinal fluid (CSF) are approximately half of those in plasma, measured after 4-week quetiapine treatment. Moreover, quetiapine administration should result in a highly significantly correlation between quetiapine in plasma and quetiapine in CSF concentrations. 2. Neurotransmitters and neuropeptides: Dysregulation of the serotonergic and dopaminergic systems as well as altered hypothalamic-pituitary-adrenal (HPA) axis are likely, but not necessary involved in pathophysiology of schizophrenia. Thus, accumulated evidence indicates that NPY, as well as CRF, also play a role. Preliminary exploratory information will be obtained on: 2.1. The relative concentrations of neuropeptides e.g. NPY and CRF measured at pre-treatment and after quetiapine medication period and the relationship with clinical improvement. To date no published data are available on this issue. The determinations of NPY and CRF in CSF, measured at b | — |
Countries
Germany
Outcome results
None listed