Bipolar Depression
Conditions
Keywords
Keppra, Levetiracetam, Anticonvulsant, Depression, Bipolar Disorder, Affective Disorders, Mood Disorders, Double Blind, Acute Antidepressant Effects
Brief summary
A 6-week outpatient, double-blind, placebo-controlled, add-on trial to investigate the effects of levetiracetam on depressive symptoms in bipolar depressed patients.
Interventions
DRUGLevetiracetam
Flexible dose up to 2500mg per day, for 6 weeks.
DRUGPlacebo
Flexible dose up to 2500mg per day, for 6 weeks.
Sponsors
Stanley Medical Research Institute
Yale University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* DSM-IV diagnosis of bipolar disorder * Presence of a current major depressive episode on the SCID * Score of 17 or great on the HDRS * Capable of giving voluntary written consent
Exclusion criteria
* Significant current substance dependence/abuse within 3 months preceding the trial * Active suicidal ideation * Pregnant/lactating mothers * Significant medical history
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Hamilton Depression Rating Scale (HDRS-21) Total Score From Baseline at Week 6. | Baseline to week 6 | Change is observed value at each visit minus baseline value. HDRS-21 is a 21-item instrument measuring depression. Items are rated on a scale from 0 (symptoms not present) to a maximum of 2 to 4 (symptom extremely severe) for a total score range of 0 to 60. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score From Baseline at Week 6. | Baseline to week 6 | Change is observed value at each visit minus baseline value. MADRS is a 10-item instrument measuring depression: scale range between 0(normal) - 6(most abnormal)for each item. Total possible score is 0 - 60. |
| Number of Subjects Who Achieve Remission. | Week 6 | Remission response is measured as an HDRS-21 total score is less than or equal to 7. HDRS-21 measures range of depressive symptoms. Endpoint is LOCF. |
| Change in Clinical Global Impressions Scale for Bipolar Disorder (CGI-BP) Depression Severity Rating From Baseline at Week 6. | Baseline to week 6 | Change is observed value at each visit minus baseline value. CGI-BP depression severity is an instrument which measures severity of depression in bipolar disorder. Scale range: 1=normal, not ill; 7=very severely ill |
Countries
United States
Participant flow
Recruitment details
Subjects were recruited from 2005-2008 from New Haven, CT and surrounding areas.
Participants by arm
| Arm | Count |
|---|---|
| Levetiracetam Subjects on active study medication. | 19 |
| Placebo Subjects assigned to placebo control group. | 16 |
| Total | 35 |
Baseline characteristics
| Characteristic | Placebo | Levetiracetam | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 16 Participants | 19 Participants | 35 Participants |
| Age, Continuous | 42.4 years STANDARD_DEVIATION 9.6 | 45.5 years STANDARD_DEVIATION 10.7 | 44.1 years STANDARD_DEVIATION 10.2 |
| Region of Enrollment United States | 16 participants | 19 participants | 35 participants |
| Sex: Female, Male Female | 9 Participants | 11 Participants | 20 Participants |
| Sex: Female, Male Male | 7 Participants | 8 Participants | 15 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 17 / 19 | 15 / 16 |
| serious Total, serious adverse events | 0 / 19 | 0 / 16 |
Outcome results
Primary
Change in Hamilton Depression Rating Scale (HDRS-21) Total Score From Baseline at Week 6.
Change is observed value at each visit minus baseline value. HDRS-21 is a 21-item instrument measuring depression. Items are rated on a scale from 0 (symptoms not present) to a maximum of 2 to 4 (symptom extremely severe) for a total score range of 0 to 60.
Time frame: Baseline to week 6
Population: Weeks 1-6 are Intent to treat (ITT) population Observed Cases. All participants included received at least 1 dose of study intervention and at least 1 assessment post-baseline.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Levetiracetam | Change in Hamilton Depression Rating Scale (HDRS-21) Total Score From Baseline at Week 6. | Week 4 (n=11, n=13) | -4.3534 score on scale | Standard Error 1.6582 |
| Levetiracetam | Change in Hamilton Depression Rating Scale (HDRS-21) Total Score From Baseline at Week 6. | Week 2 (n=15, n=14) | -3.4259 score on scale | Standard Error 1.4618 |
| Levetiracetam | Change in Hamilton Depression Rating Scale (HDRS-21) Total Score From Baseline at Week 6. | Week 5 (n=11, n=13) | -6.952 score on scale | Standard Error 1.7105 |
| Levetiracetam | Change in Hamilton Depression Rating Scale (HDRS-21) Total Score From Baseline at Week 6. | Week 1 (n=17, n=15) | -2.7647 score on scale | Standard Error 1.4138 |
| Levetiracetam | Change in Hamilton Depression Rating Scale (HDRS-21) Total Score From Baseline at Week 6. | Week 6 (n=10, n=11) | -4.8136 score on scale | Standard Error 1.7806 |
| Levetiracetam | Change in Hamilton Depression Rating Scale (HDRS-21) Total Score From Baseline at Week 6. | Week 3 (n=13, n=14) | -2.1243 score on scale | Standard Error 1.5441 |
| Placebo | Change in Hamilton Depression Rating Scale (HDRS-21) Total Score From Baseline at Week 6. | Week 6 (n=10, n=11) | -7.0712 score on scale | Standard Error 1.6838 |
| Placebo | Change in Hamilton Depression Rating Scale (HDRS-21) Total Score From Baseline at Week 6. | Week 1 (n=17, n=15) | -4 score on scale | Standard Error 1.5051 |
| Placebo | Change in Hamilton Depression Rating Scale (HDRS-21) Total Score From Baseline at Week 6. | Week 2 (n=15, n=14) | -6.5875 score on scale | Standard Error 1.5327 |
| Placebo | Change in Hamilton Depression Rating Scale (HDRS-21) Total Score From Baseline at Week 6. | Week 4 (n=11, n=13) | -6.3851 score on scale | Standard Error 1.583 |
| Placebo | Change in Hamilton Depression Rating Scale (HDRS-21) Total Score From Baseline at Week 6. | Week 5 (n=11, n=13) | -6.4368 score on scale | Standard Error 1.6006 |
| Placebo | Change in Hamilton Depression Rating Scale (HDRS-21) Total Score From Baseline at Week 6. | Week 3 (n=13, n=14) | -6.3625 score on scale | Standard Error 1.5458 |
Comparison: Comparison of changes in outcome between treatment groups at week 6.p-value: 0.29Mixed Models Analysis
Secondary
Change in Clinical Global Impressions Scale for Bipolar Disorder (CGI-BP) Depression Severity Rating From Baseline at Week 6.
Change is observed value at each visit minus baseline value. CGI-BP depression severity is an instrument which measures severity of depression in bipolar disorder. Scale range: 1=normal, not ill; 7=very severely ill
Time frame: Baseline to week 6
Population: Weeks 1-6 are Intent to treat (ITT) population Observed Cases. All participants included received at least 1 dose of study intervention and at least 1 assessment post-baseline.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Levetiracetam | Change in Clinical Global Impressions Scale for Bipolar Disorder (CGI-BP) Depression Severity Rating From Baseline at Week 6. | Week 4 (n=11, n=13) | -0.3729 score on scale | Standard Error 0.2386 |
| Levetiracetam | Change in Clinical Global Impressions Scale for Bipolar Disorder (CGI-BP) Depression Severity Rating From Baseline at Week 6. | Week 1 (n=17, n=15) | -0.2941 score on scale | Standard Error 0.1982 |
| Levetiracetam | Change in Clinical Global Impressions Scale for Bipolar Disorder (CGI-BP) Depression Severity Rating From Baseline at Week 6. | Week 3 (n=13, n=14) | -0.1984 score on scale | Standard Error 0.2207 |
| Levetiracetam | Change in Clinical Global Impressions Scale for Bipolar Disorder (CGI-BP) Depression Severity Rating From Baseline at Week 6. | Week 2 (n=14, n=14) | -0.3186 score on scale | Standard Error 0.211 |
| Levetiracetam | Change in Clinical Global Impressions Scale for Bipolar Disorder (CGI-BP) Depression Severity Rating From Baseline at Week 6. | Week 6 (n=10, n=10) | -0.5742 score on scale | Standard Error 0.2539 |
| Levetiracetam | Change in Clinical Global Impressions Scale for Bipolar Disorder (CGI-BP) Depression Severity Rating From Baseline at Week 6. | Week 5 (n=11, n=12) | -0.7325 score on scale | Standard Error 0.244 |
| Placebo | Change in Clinical Global Impressions Scale for Bipolar Disorder (CGI-BP) Depression Severity Rating From Baseline at Week 6. | Week 6 (n=10, n=10) | -0.9294 score on scale | Standard Error 0.2505 |
| Placebo | Change in Clinical Global Impressions Scale for Bipolar Disorder (CGI-BP) Depression Severity Rating From Baseline at Week 6. | Week 3 (n=13, n=14) | -0.7753 score on scale | Standard Error 0.2177 |
| Placebo | Change in Clinical Global Impressions Scale for Bipolar Disorder (CGI-BP) Depression Severity Rating From Baseline at Week 6. | Week 5 (n=11, n=12) | -0.8739 score on scale | Standard Error 0.2322 |
| Placebo | Change in Clinical Global Impressions Scale for Bipolar Disorder (CGI-BP) Depression Severity Rating From Baseline at Week 6. | Week 2 (n=14, n=14) | -0.6956 score on scale | Standard Error 0.2161 |
| Placebo | Change in Clinical Global Impressions Scale for Bipolar Disorder (CGI-BP) Depression Severity Rating From Baseline at Week 6. | Week 1 (n=17, n=15) | -0.4667 score on scale | Standard Error 0.211 |
| Placebo | Change in Clinical Global Impressions Scale for Bipolar Disorder (CGI-BP) Depression Severity Rating From Baseline at Week 6. | Week 4 (n=11, n=13) | -0.8403 score on scale | Standard Error 0.2238 |
Comparison: Comparison of changes in outcome between treatment groups.p-value: 0.79Mixed Models Analysis
Secondary
Change in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score From Baseline at Week 6.
Change is observed value at each visit minus baseline value. MADRS is a 10-item instrument measuring depression: scale range between 0(normal) - 6(most abnormal)for each item. Total possible score is 0 - 60.
Time frame: Baseline to week 6
Population: Weeks 1-6 are Intent to treat (ITT) population Observed Cases. All participants included received at least 1 dose of study intervention and at least 1 assessment post-baseline.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Levetiracetam | Change in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score From Baseline at Week 6. | Week 4 (n=11, n=13) | -5.5505 score on scale | Standard Error 2.3441 |
| Levetiracetam | Change in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score From Baseline at Week 6. | Week 2 (n=15, n=14) | -5.2319 score on scale | Standard Error 2.1105 |
| Levetiracetam | Change in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score From Baseline at Week 6. | Week 5 (n=11, n=12) | -9.9142 score on scale | Standard Error 2.3441 |
| Levetiracetam | Change in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score From Baseline at Week 6. | Week 3 (n=13, n=14) | -3.384 score on scale | Standard Error 2.2162 |
| Levetiracetam | Change in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score From Baseline at Week 6. | Week 6 (n=10, n=11) | -6.5208 score on scale | Standard Error 2.4183 |
| Levetiracetam | Change in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score From Baseline at Week 6. | Week 1 (n=17, n=15) | -3.2941 score on scale | Standard Error 2.0145 |
| Placebo | Change in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score From Baseline at Week 6. | Week 6 (n=10, n=11) | -4.5153 score on scale | Standard Error 2.3691 |
| Placebo | Change in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score From Baseline at Week 6. | Week 3 (n=13, n=14) | -9.0417 score on scale | Standard Error 2.1999 |
| Placebo | Change in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score From Baseline at Week 6. | Week 4 (n=11, n=13) | -8.7608 score on scale | Standard Error 2.2514 |
| Placebo | Change in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score From Baseline at Week 6. | Week 1 (n=17, n=15) | -2.7333 score on scale | Standard Error 2.1446 |
| Placebo | Change in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score From Baseline at Week 6. | Week 5 (n=11, n=12) | -6.6591 score on scale | Standard Error 2.3061 |
| Placebo | Change in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score From Baseline at Week 6. | Week 2 (n=15, n=14) | -7.256 score on scale | Standard Error 2.1999 |
Comparison: Comparison of changes in outcome between treatment groups at week 6.p-value: 0.07Mixed Models Analysis
Secondary
Number of Subjects Who Achieve Remission.
Remission response is measured as an HDRS-21 total score is less than or equal to 7. HDRS-21 measures range of depressive symptoms. Endpoint is LOCF.
Time frame: Week 6
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Levetiracetam | Number of Subjects Who Achieve Remission. | Remitted | 0 Participants |
| Levetiracetam | Number of Subjects Who Achieve Remission. | Not remitted | 17 Participants |
| Placebo | Number of Subjects Who Achieve Remission. | Remitted | 4 Participants |
| Placebo | Number of Subjects Who Achieve Remission. | Not remitted | 11 Participants |
Comparison: Week 6p-value: 0.038Fisher Exact