Official Title: “Oxcarbazepine as an Adjunct of Antipsychotic Therapy in Acute Schizophrenia”

Over recent years an approach with the adjunctive administration of various anticonvulsant drugs has been discussed and a limited number of open and controlled studies were performed for carbamazepine, valproic acid, and lamotrigine. While the latter shows promising effects in the long run it has some handling difficulties in the acute treatment of acute psychotic exacerbations. Valproic acid has shown inconsistent effects in schizophrenia with no significant effects in a recent controlled study. Although still controversially discussed, carbamazepine was found to offer beneficial effects in the treatment of schizophrenia.

Nonetheless, data on these effects are limited by small sample sizes or poor design of most of the respective studies.

Furthermore, the complex pharmacological interactions of new atypical neuroleptics with carbamazepine underline the necessity of alternative strategies in adjuvant treatment of schizophrenia as well as in combined treatment of bipolar disorders with mood stabilizers and neuroleptics.

Oxcarbazepine (OXC) is a new anticonvulsant drug that acts as a pro-drug for the 10-monohydroxy metabolite (MHD), an active metabolite also of carbamazepine that is suggested to be responsible for most of its therapeutic actions. Therefore, the pharmacological action of OXC is very well comparable to carbamazepine whilst there are fewer unwanted side effects of OXC regarding eg. skin rush, and effects on blood compounds or cardiotropic effects. The effects of OXC on cytochrome CYP3A4 and CYP3A5 are moderate and UDPGT is only slightly affected by OXC, which leads to less interaction with other compounds on a pharmacokinetical level. In psychiatry, the few studies published until now report positive effects of OXC in bipolar disorders. With regards to our own clinical observations, OXC has shown potential beneficial effects as an adjunct in the treatment of schizophrenia as well that require further evaluation in a controlled study design.

Study Type: Interventional

Study Design: Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment, Safety/Efficacy Study

Study Primary Completion Date: April 2008

This is an explorative controlled study with Oxcarbazepine (OXC) as an adjunct in the acute treatment of schizophrenia. The study will be performed in subjects between 18 and 50 years of age with an acute schizophrenic or schizophreniform disorder according to DSM-IV. The study will be performed according to Guidelines for Good Clinical Practice (GCP). The primary hypothesis of this study is that adjunctive treatment with OXC yields at least comparable efficacy regarding antipsychotic actions with lower doses of neuroleptics and consequently substantially fewer adverse events. A randomised controlled, double blind study is intended.

During a 6 weeks treatment trial two groups of patients will be basically treated with olanzapine (starting with 5 mg after one week with an optional, BPRS-controlled step by step increase of about 2,5 mg each following week). Patients will receive a placebo controlled adjunctive therapy with OXC (1800 mg/day). After the initial lead-in of OXC within 7 days (allowing lorazepam as comedication), treatment with olanzapine will be started. Based on biometric calculations, a drop out adjusted sample size of 222 inpatients will be necessary

Intervention(s) in this Clinical Trial

• Drug: Oxcarbazepine
  • Oxcarbazepine (OXC), 300 mg tablets, up to 600 mg three times daily
• Drug: Placebo
  • Placebo, 300 mg tablets, up to 600 mg three times daily

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: 1
• Placebo Comparator: 2

Primary Measures

• Amount of Olanzapine Co-medication
  • Time Frame: 5 weeks
    Safety Issue?: No

Secondary Measures

• BPRS
  • Time Frame: 6 weeks
    Safety Issue?: No
• Extrapyramidal symptoms
  • Time Frame: 6 weeks
    Safety Issue?: Yes
• Weight gain
  • Time Frame: 6 weeks
    Safety Issue?: Yes
• Prolactin levels in plasma
  • Time Frame: 6 weeks
    Safety Issue?: Yes
• ECG QT-C time elongation
  • Time Frame: 6 weeks
    Safety Issue?: Yes
• Neurocognitive performance
  • Time Frame: 6 week
    Safety Issue?: No

Inclusion Criteria:

• Clinical diagnosis of schizophrenia or schizophreniform psychosis according to DSM-IV
• BPRS score > 36 and BPRS psychosis cluster > 12
• Ability to provide written informed consent
• Participants are required an adequate contraception

Exclusion Criteria:

• Any severe neurological or somatic disorder
• Other psychiatric disorders including addictive disorders
• Positive urine drug screening for any compound except benzodiazepines
• No pregnancy or breast feeding

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: 65 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: University of Cologne

Overall Clinical Trial Officials and Contacts

F. Markus Leweke, MD Study Director University of Cologne  

Information obtained from ClinicalTrials.gov on July 02, 2009

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00637234

Study ID Number: OXC-SCZ CTRI476BDE06

ClinicalTrials.gov Identifier: NCT00637234

Health Authority: Germany: Federal Institute for Drugs and Medical Devices