Oxcarbazepine as an Adjunct of Antipsychotic Therapy in Acute Schizophrenia
Condition: Schizophrenia
MeSH terms: Schizophrenia
Study type: Interventional
Phase: Phase 2/Phase 3

Summary: 
      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.
    

Detailed description: 
      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 name(s): Oxcarbazepine; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): Oxcarbazepine (OXC), 300 mg tablets, up to 600 mg three times daily; Placebo, 300 mg tablets, up to 600 mg three times daily
Other intervention name(s): Trileptal FCT 300MG.002; Film-coated tablet; Batch No.: X208 0802; Code: 3750031.002; Date of manufacture: September 2002; Date of evaluation: May 2004; TRL PLA FCT.005; Film-coated tablet; Batch No.: X207 0802; Code: 3750411.005; Date of manufacture: September 2002; Date of evaluation: May 2004
Intervention MeSH terms: Oxcarbazepine
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment