Schizophrenia
Conditions
Keywords
Schizophrenia, Anticonvulsants, Valproic Acid, Valproate
Brief summary
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
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.
Interventions
DRUGValproate
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.
Sponsors
Abbott
University Hospitals Cleveland Medical Center
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
50 Years to No maximum
Healthy volunteers
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Schizophrenia Psychopathology as Assessed by the Positive and Negative Symptom Scale (PANSS) | Baseline to 12 weeks | The best and worst possible overall PANSS scores are 30 and 210 units on a scale, respectively. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Overall Functioning as Measured by the Global Assessment Scale (GAS) | Baseline to 12 weeks | The best and worst possible GAS scores are 100 and 1 units on a scale, respectively. |
| Change in Depression Symptoms as Measured by the Geriatric Depression Scale (GDS) | Baseline to 12 weeks | The best and worst possible GDS scores are 0 and 30 units on a scale, respectively. |
| Change in Overall Mental Health Status as Measure by the Mental Composite Score (MCS) Subscale of the Short Form 36 Health Survey (SF-36) | Baseline to 12 weeks | The best and worst possible MCS scores are 100 and 1 units on a scale, respectively. |
| Change in Physical Health Status as Measure by the Physical Composite Score (PCS) Subscale of the Short Form 36 Health Survey (SF-36) | Baseline to 12 weeks | The best and worst possible PCS scores are 100 and 0 units on a scale, respectively. |
| Change in Cognitive Status as Measured by the Mini-mental State Examination (MMSE) | Baseline to 12 weeks | The best and worst possible overall scores are 31 and 0 units on a scale, respectively. |
| Change in Extrapyramidal Symptoms as Assessed by the Simpson Angus Neurological Rating Scale (SAS) | Baseline to 12 weeks | The best and worst possible overall scores are 40 and 0 units on a scale, respectively. |
| Tolerability as Assessed by Weight Change | Baseline to 12 weeks | — |
| Tolerability as Measured by Mean Serum Level at Study Endpoint | Baseline to 12 weeks | — |
| Change in Extrapyramidal Symptoms as Assessed by the Abnormal Involuntary Movement Scale (AIMS) | Baseline to 12 weeks | The best and worst possible overall scores are 0 and 28 units on a scale, respectively. |
Countries
United States
Participant flow
Recruitment details
The study was conducted at an academic psychiatry clinic in the mid-western United States. Data was collected from participants from February 2004 to November 2006. Participants were recruited in response to self-referrals from advertisements and by referrals from mental health practitioners.
Participants by arm
| Arm | Count |
|---|---|
| Valproate Enrolled individuals received adjunctive, openlabel 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 mg/mL. In cases where sedation or other side effects occurred, dosage was reduced. Valproate semisodium was prescribed in a single dose at bedtime. | 20 |
| Total | 20 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
| Overall Study | non-adherence with study medication | 4 |
Baseline characteristics
| Characteristic | Valproate |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 5 Participants |
| Age, Categorical Between 18 and 65 years | 15 Participants |
| Age, Continuous | 61.1 years STANDARD_DEVIATION 9.6 |
| Region of Enrollment United States | 20 participants |
| Sex: Female, Male Female | 16 Participants |
| Sex: Female, Male Male | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 20 |
| serious Total, serious adverse events | 0 / 20 |
Outcome results
Primary
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.
Time frame: Baseline to 12 weeks
Population: Last Observation Carried Forward (LOCF) was used as the imputation technique.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Valproate | Change in Schizophrenia Psychopathology as Assessed by the Positive and Negative Symptom Scale (PANSS) | -17.45 scores on a scale | Standard Deviation 14.87 |
Comparison: The 1 sided t-test was applied to the scores at baseline vs. the scores at 12 weeks.p-value: <0.001t-test, 1 sided
Secondary
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.
Time frame: Baseline to 12 weeks
Population: Last Observation Carried Forward (LOCF) was used as the imputation technique.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Valproate | Change in Cognitive Status as Measured by the Mini-mental State Examination (MMSE) | 0.4 scores on a scale | Standard Deviation 3.218 |
Comparison: The 1 sided t-test was applied to the scores at baseline vs. the scores at 12 weeks.p-value: 0.585t-test, 1 sided
Secondary
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.
Time frame: Baseline to 12 weeks
Population: Last Observation Carried Forward (LOCF) was used as the imputation technique.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Valproate | Change in Depression Symptoms as Measured by the Geriatric Depression Scale (GDS) | -1.556 scores on a scale | Standard Deviation 2.502 |
Comparison: The 1 sided t-test was applied to the scores at baseline vs. the scores at 12 weeks.p-value: 0.017t-test, 1 sided
Secondary
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.
Time frame: Baseline to 12 weeks
Population: Last Observation Carried Forward (LOCF) was used as the imputation technique.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Valproate | Change in Extrapyramidal Symptoms as Assessed by the Abnormal Involuntary Movement Scale (AIMS) | -2.105 scores on a scale | Standard Deviation 4.108 |
Comparison: The 1 sided t-test was applied to the scores at baseline vs. the scores at 12 weeks.p-value: 0.038t-test, 1 sided
Secondary
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.
Time frame: Baseline to 12 weeks
Population: Last Observation Carried Forward (LOCF) was used as the imputation technique.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Valproate | Change in Extrapyramidal Symptoms as Assessed by the Simpson Angus Neurological Rating Scale (SAS) | -0.6 scores on a scale | Standard Deviation 1.724 |
Comparison: The 1 sided t-test was applied to the scores at baseline vs. the scores at 12 weeks.p-value: 0.199t-test, 1 sided
Secondary
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.
Time frame: Baseline to 12 weeks
Population: Last Observation Carried Forward (LOCF) was used as the imputation technique.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Valproate | Change in Overall Functioning as Measured by the Global Assessment Scale (GAS) | 16.35 scores on a scale | Standard Deviation 15.09 |
Comparison: The 1 sided t-test was applied to the scores at baseline vs. the scores at 12 weeks.p-value: <0.001t-test, 1 sided
Secondary
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.
Time frame: Baseline to 12 weeks
Population: The number of participants for analysis was based on available data. Last Observation Carried Forward (LOCF) was used as the imputation technique.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Valproate | Change in Overall Mental Health Status as Measure by the Mental Composite Score (MCS) Subscale of the Short Form 36 Health Survey (SF-36) | 5.298 scores on a scale | Standard Deviation 7.968 |
Comparison: The 1 sided t-test was applied to the scores at baseline vs. the scores at 12 weeks.p-value: 0.027t-test, 1 sided
Secondary
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.
Time frame: Baseline to 12 weeks
Population: Last Observation Carried Forward (LOCF) was used as the imputation technique.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Valproate | Change in Physical Health Status as Measure by the Physical Composite Score (PCS) Subscale of the Short Form 36 Health Survey (SF-36) | 0.932 scores on a scale | Standard Deviation 5.971 |
Comparison: The 1 sided t-test was applied to the scores at baseline vs. the scores at 12 weeks.p-value: 0.569t-test, 1 sided
Secondary
Tolerability as Assessed by Weight Change
Time frame: Baseline to 12 weeks
Population: All available data was used implementing LOCF.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Valproate | Tolerability as Assessed by Weight Change | 1.1 kilograms | Standard Deviation 3.6 |
Comparison: The t-test was applied to the values at baseline vs. the values at 12 weeks.p-value: 0.21t-test, 2 sided
Secondary
Tolerability as Measured by Mean Serum Level at Study Endpoint
Time frame: Baseline to 12 weeks
Population: Last Observation Carried Forward (LOCF) was used as the imputation technique.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Valproate | Tolerability as Measured by Mean Serum Level at Study Endpoint | 40.86 ug/mL | Standard Deviation 25.29 |