Dopaminergic, Functional, Structural, and Cognitive Disturbances in First-episode Schizophrenia
- Full Text View
- Tabular View
- No Study Results Posted
- Disclaimer
- How to Read a Study Record
Purpose
We wanted to compare dopamine D2 receptor activity, brain structure, brain function, sensory gating and cognition in neuroleptic-naive schizophrenic patients and matched healthy controls. Additionally, we wanted to examine the effects of 3 months of treatment with either low doses of a typical or an atypical antipsychotic compound on the same functions. The hypotheses were that schizophrenic patients suffered from disturbances in brain function and structure, information processing, and extrastriatal D2 receptor activity, and that these disturbances would be related to each other and to psychopathology. Additionally, we expected the atypical compound to have an effect on some of the disturbances in information processing, and that the atypical compound - in contrast to the typical drug - would show extrastriatal over striatal selectivity.
| Condition | Intervention |
|---|---|
|
Schizophrenia |
Drug: zuclopenthixol Drug: risperidone |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Pharmacodynamics Study Intervention Model: Factorial Assignment Masking: Open Label Primary Purpose: Diagnostic |
| Official Title: | Effects of Classical and Atypical Antipsychotics on Dopamine Receptor Binding of 123I-epidepride, Cognition, Startle Response and Extrapyramidal Side-effects in Drug-naive First-episode Schizophrenic Patients |
- All examinations are done at baseline (patients and controls). In the patient group, they are repeated after 3 months of treatment [ Time Frame: prospective ] [ Designated as safety issue: No ]
- PANSS [ Time Frame: prospective ] [ Designated as safety issue: No ]
- SANS [ Time Frame: prospective ] [ Designated as safety issue: No ]
- SAPS [ Time Frame: prospective ] [ Designated as safety issue: No ]
- MRI [ Time Frame: prospective ] [ Designated as safety issue: Yes ]
- fMRI [ Time Frame: prospective ] [ Designated as safety issue: No ]
- startle response [ Time Frame: prospective ] [ Designated as safety issue: No ]
- PrePulse Inhibition of the startle response (PPI) [ Time Frame: prospective ] [ Designated as safety issue: No ]
- Cognition [ Time Frame: prospective ] [ Designated as safety issue: No ]
- The cognitive test battery comprised tests from the Cambridge Neuropsychological Test Automated Battery (CANTAB) as well as paper-and-pencil cognitive tests. [ Time Frame: prospective ] [ Designated as safety issue: No ]
| Enrollment: | 56 |
| Study Start Date: | January 1998 |
| Study Completion Date: | September 2010 |
| Primary Completion Date: | September 2010 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
| Active Comparator: 1 |
Drug: zuclopenthixol
Patients will be administered zuclopenthixol orally in doses between 4 -24 mg/day, depending on an effective reduction of symptoms
Other Name: Cisordinol
|
| Active Comparator: 2 |
Drug: risperidone
Patients will be administered risperidone orally in doses between 1-6 mg/day, depending on an effective reduction of symptoms
Other Name: Risperdal
|
Detailed Description:
31 neuroleptic-naive schizophrenic patients and 25 matched controls were recruited from the greater Copenhagen area. The patients were randomized to treatment with either low doses of the typical antipsychotic compound, zuclopenthixol, or the atypical drug, risperidone. Patients and controls were examined at base-line and patients were re-examined after 3 months of treatment.The study has resulted in two finish Ph.D. theses (Torben Mackeprang and Birgitte Fagerlund).
The data has in part been published in:
Mackeprang T, Tjelle Kristiansen K, Glenthoj B. Prepulse inhibition of the startle response in drug-naïve, first-episode schizophrenic patients before and after 3 months of treatment with a typical or an atypical antipsychotic drug. Biological Psychiatry 2002; 52(9): 863-873.
and
Fagerlund B, Mackeprang T, Gade A, Hemmingsen R, Glenthoj BY. Effects of Low-Dose Risperidone and Low-Dose Zuclopenthixol on Cognitive Functions in First-Episode Drug-Naïve Schizophrenic Patients. CNS Spectr. 2004; 9: 364-74.
and
Glenthoj BY, Mackeprang T, Svarer C, Rasmussen H, Pinborg L, Friberg L, Baaré W, Hemmingsen R, Videbæk C. Frontal dopamine D2/3 receptor binding in drug-naïve first-episode schizophrenic patients correlates with positive psychotic symptoms and gender. Biological Psychiatry 2006; in press. Mar 30; [Epub ahead of print]. PMID: 16784819 [PubMed - as supplied by publisher].
We are at present conducting a five-year follow-up study of the same cohort of patients and controls and plan a ten-year follow-up as well. The follow-up studies focus on brain structure (MRI), brain function, information processing, and psychopathology. We will correlate changes in structure and function to treatment, but no interventions (pharmacological or otherwise) are planned.
Eligibility| Ages Eligible for Study: | 18 Years to 45 Years |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | Yes |
Inclusion Criteria:
- For patients: Clinical diagnosis of schizophrenia.
- The controls were matched to the patients.
Exclusion Criteria:
- Patients: Previous antipsychotic treatment, patients who were compulsorily hospitalised or deemed in acute need of medication, mental retardation
- Controls: psychiatric diagnosis, psychiatric diagnosis in first-degree relatives, drug abuse, mental retardation
Contacts and Locations| Denmark | |
| Neurobiology Research Unit, University of Copenhagen, Rigshospitalet | |
| Copenhagen, Denmark, DK-2100 | |
| Dept. of Nuclear Medicine, University of Copenhagen, Bispebjerg Hospital | |
| Copenhagen NV, Denmark, DK-2400 | |
| University of Copenhagen, Dept. F, Bispebjerg Hospital | |
| Copenhagen NV, Denmark, DK-2400 | |
| University of Copenhagen, Dept. of Psychiatry E, Bispebjerg Hospital | |
| Copenhagen NV, Denmark, DK-2400 | |
| Center for Neuropsychiatric Schizophrenia Research, University of Copenhagen, Psychiatric Center Glostrup | |
| Glostrup, Denmark, DK-2600 | |
| Danish Research Center for Magnetic Resonance Imaging, Hvidovre Hospital | |
| Hvidovre, Denmark, DK-2650 | |
| Study Director: | Birte Glenthoj, MD, DMSc | University of Copenhagen, Psychiatric Center Glostrup, Ndr. Ringvej, DK-2600 Glostrup, Denmark |
More Information
Publications:
| Responsible Party: | Birte Glenthoj, Professor of Psychopharmacology and Neuropsychiatry, Danish Center for Neuropsychiatric Schizophrenia Research, University of Copenhagen |
| ClinicalTrials.gov Identifier: | NCT00206960 History of Changes |
| Other Study ID Numbers: | 363002, KF 01-078/97, KF 01-012/98, KF 11-057/99 |
| Study First Received: | September 10, 2005 |
| Last Updated: | September 16, 2011 |
| Health Authority: | Denmark: National Board of Health |
Keywords provided by University of Copenhagen:
|
drug-naive epidepride single tomography D2 receptor information processing |
PPI antipsychotic treatment MRI fMRI cognitive disturbances |
Additional relevant MeSH terms:
|
Schizophrenia Schizophrenia and Disorders with Psychotic Features Mental Disorders Clopenthixol Risperidone Clopenthixol acetate ester Antipsychotic Agents Dopamine Antagonists Dopamine Agents Neurotransmitter Agents |
Molecular Mechanisms of Pharmacological Action Pharmacologic Actions Physiological Effects of Drugs Tranquilizing Agents Central Nervous System Depressants Central Nervous System Agents Therapeutic Uses Psychotropic Drugs Serotonin Antagonists Serotonin Agents |
ClinicalTrials.gov processed this record on May 16, 2013