Official Title: “Add-on Valproate in Late Life Schizophrenia”

The purpose of this research study is to analyze the effectiveness and tolerability of a medication, valproate ( Depakote and Depakote ER), in individuals age 50 years and older who have schizophrenia.

Study Type: Interventional

Study Design: Treatment, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Safety/Efficacy Study

Study Primary Completion Date: November 2006

It is known that up to 30% of individuals with schizophrenia continue to have symptoms even when treated with current FDA-approved medications intended to treat their schizophrenia.

Anticonvulsant medications such as valproate (Depakote and Depakote ER) are known to be effective for related conditions such as bipolar disorder (manic depressive illness), and are also used by some physicians in clinical settings in combination with antipsychotic medications to treat symptoms of schizophrenia. Currently Depakote and Depakote ER are approved by the FDA to treat bipolar disorder and to treat seizure disorder. This study will test to see if Depakote and Depakote ER may improve symptoms of schizophrenia as well when added to antipsychotic medications.

Intervention(s) in this Clinical Trial

• Drug: Valproate
  • Enrolled individuals received adjunctive, open-label valproate semisodium, initially started as valproate semisodium delayed -release 250 mg at bedtime for two weeks, then changed to valproate semisodium extended- release 500 mg at bedtime. Medication was administered on an outpatient/ambulatory basis, and adjusted as tolerated to target serum levels of 50-100 µg/mL. In cases where sedation or other side effects occurred, dosage was reduced. Valproate semisodium was prescribed in a single dose at bedtime.

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: 1

Primary Measures

• Efficacy:
  • Time Frame: 12 weeks
    Safety Issue?: No
• Positive and Negative Symptom Scale (PANSS) - Baseline and weeks 2, 4, 8, and 12/study end
  • Time Frame: 12 weeks
    Safety Issue?: No
• Geriatric Depression Scale (GDS) - Baseline and weeks 2, 4, 8, and 12/study end
  • Time Frame: 12 weeks
    Safety Issue?: No
• Clinical Global Impression (CGI) - Baseline and weeks 2, 4, 8, and 12/study end
  • Time Frame: 12 weeks
    Safety Issue?: No
• Tolerability:
  • Time Frame: 12 weeks
    Safety Issue?: Yes
• Chemistry panel - baseline and week 12/study end
  • Time Frame: 12 weeks
    Safety Issue?: Yes
• Lipid profile - baseline and week 12/study end
  • Time Frame: 12 weeks
    Safety Issue?: Yes
• CBC with differential - baseline and week 12/study end
  • Time Frame: 12 weeks
    Safety Issue?: Yes
• Valproate serum levels - weeks 2, 4, 8, and 12
  • Time Frame: 12 weeks
    Safety Issue?: Yes
• Abnormal Involuntary Movement Scale (AIMS) - Baseline and weeks 2, 4, 8, and 12/study end
  • Time Frame: 12 weeks
    Safety Issue?: No
• Barnes Akathisia Scale - Baseline and weeks 2, 4, 8, and 12/study end
  • Time Frame: 12 weeks
    Safety Issue?: No
• Simpson Angus Neurological Rating Scale - Baseline and weeks 2, 4, 8, and 12/study end
  • Time Frame: 12 weeks
    Safety Issue?: No

Secondary Measures

• Cognitive status as measured by the Mini-mental state examination (MMSE) - Baseline and weeks 2, 4, 8, and 12/study end
  • Time Frame: 12 weeks
    Safety Issue?: No
• Overall functioning as measured by the Global Assessment Scale (GAS) - Baseline and weeks 2, 4, 8, and 12/study end
  • Time Frame: 12 weeks
    Safety Issue?: No
• General health status as measure by the Short form 36 Health Survey (SF-36) - Baseline and weeks 2, 4, 8, and 12/study end
  • Time Frame: 12 weeks
    Safety Issue?: No

Inclusion Criteria:

• Must have a diagnosis of schizophrenia as confirmed by the MINI
• Must be on antipsychotic medication
• Must be age 50 year or older
• Must be capable of providing written informed consent for study participation. In situations where individuals have guardians of person, guardian and subject must both provide written consent; and
• Must live in the Northeast Ohio area.

Exclusion Criteria:

• A primary psychiatric DSM Axis I diagnosis other than schizophrenia
• Actively abusing substances; or
• Medically unstable.

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 50 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: University Hospitals of Cleveland

Overall Clinical Trial Officials and Contacts

Martha Sajatovic, MD Principal Investigator Case Western Reserve University School of Medicine  

Information obtained from ClinicalTrials.gov on August 29, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00194025

Study ID Number: 10850-01-L0348

ClinicalTrials.gov Identifier: NCT00194025

Health Authority: United States: Institutional Review Board