Valproate in Late Life Schizophrenia

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Add-on Valproate in Late Life Schizophrenia

Conditions
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Schizophrenia

Intervention / Treatment
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* Drug: Valproate


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: valproate<br>All participants received open-label, add-on valproate. | Drug: Valproate<br>* 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.<br>* Other names: Depakote ER;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Schizophrenia Psychopathology as Assessed by the Positive and Negative Symptom Scale (PANSS) | The best and worst possible overall PANSS scores are 30 and 210 units on a scale, respectively. | Baseline to 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Cognitive Status as Measured by the Mini-mental State Examination (MMSE) | The best and worst possible overall scores are 31 and 0 units on a scale, respectively. | Baseline to 12 weeks | 
| Change in Overall Functioning as Measured by the Global Assessment Scale (GAS) | The best and worst possible GAS scores are 100 and 1 units on a scale, respectively. | Baseline to 12 weeks | 
| Change in Depression Symptoms as Measured by the Geriatric Depression Scale (GDS) | The best and worst possible GDS scores are 0 and 30 units on a scale, respectively. | Baseline to 12 weeks | 
| Change in Overall Mental Health Status as Measure by the Mental Composite Score (MCS) Subscale of the Short Form 36 Health Survey (SF-36) | The best and worst possible MCS scores are 100 and 1 units on a scale, respectively. | Baseline to 12 weeks | 
| Change in Physical Health Status as Measure by the Physical Composite Score (PCS) Subscale of the Short Form 36 Health Survey (SF-36) | The best and worst possible PCS scores are 100 and 0 units on a scale, respectively. | Baseline to 12 weeks | 
| Change in Extrapyramidal Symptoms as Assessed by the Abnormal Involuntary Movement Scale (AIMS) | The best and worst possible overall scores are 0 and 28 units on a scale, respectively. | Baseline to 12 weeks | 
| Change in Extrapyramidal Symptoms as Assessed by the Simpson Angus Neurological Rating Scale (SAS) | The best and worst possible overall scores are 40 and 0 units on a scale, respectively. | Baseline to 12 weeks | 
| Tolerability as Assessed by Weight Change |  | Baseline to 12 weeks | 
| Tolerability as Measured by Mean Serum Level at Study Endpoint |  | Baseline to 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Schizophrenia, Anticonvulsants, Valproic Acid, Valproate