Bipolar Disorder
Conditions
Keywords
Bipolar, Depression
Brief summary
The Johns Hopkins Department of Psychiatry is conducting a research study to examine the effectiveness of riluzole in treating the depressed phase of bipolar disorder. This outpatient treatment study of medication or placebo will last 9-12 weeks. The study includes medical and psychiatric evaluations as well as time-limited medication treatment at no cost, and you will be compensated for your participation.
Detailed description
The study will last 8 to 12 weeks and requires weekly visits. Participants will come to Johns Hopkins for a screening visit during which they will talk with a psychiatrist, answer questions about their mood and symptoms, have their blood drawn and have a brief physical exam. If they meet criteria for the study, any antidepressant medication that they are taking will be tapered and stopped before beginning study medications. Participation in the study includes free study medication, labs, and testing plus reimbursement for transportation. Participants will also be paid and after the study referred back to their treating psychiatrist with treatment recommendations.
Interventions
DRUGRiluzole
Initially dispensed 50 mg capsules to take twice a day (BID). At two weeks, increase dose to 50 mg/100 mg. At four weeks increase to 100 mg BID (two capsules in the morning (qAM), two capsules in the evening (qHS). If significant side effects occur (at any time), titration can be slowed and doses can be reduced to a minimum daily dose of 50 mg/day, after which titration may resume by no more than 50 mg a week. Subjects who are unable to tolerate the minimal daily dose permitted in the study will be discontinued from further participation. In addition, if clinical remission is observed at a lower dose of study medication (defined as Montgomery Asberg Depression Rating Scale (MADRS) \< 12) the dose will not be increased further unless clinical symptoms recur.
OTHERPlacebo
Initially dispensed 50mg capsules to take BID. At two weeks increase dose to 50 mg/100 mg. At four weeks increase to 100 mg BID (two capsules qAM, two capsules qHS). If significant side effects occur (at any time), titration can be slowed and doses can be reduced to a minimum daily dose of 50 mg/day, after which titration may resume by no more than 50 mg a week. Subjects who are unable to tolerate the minimal daily dose permitted in the study will be discontinued from further participation. In addition, if clinical remission is observed at a lower dose of study medication (defined as MADRS \< 12) the dose will not be increased further unless clinical symptoms recur.
Sponsors
Stanley Medical Research Institute
Johns Hopkins 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 75 Years
Healthy volunteers
No
Inclusion criteria
* Ages 18-75 * Diagnosed with Bipolar I or II disorder and currently depressed * Tried at least one antidepressant during the current episode of depression * Currently taking either lithium, depakote, or tegretol * Currently in outpatient treatment with a psychiatrist
Exclusion criteria
* Current psychotic symptoms * Women who are pregnant or nursing * Any serious, uncontrolled medical illness * History of liver problems * Current or past blood diseases * Current drug or alcohol abuse * Currently receiving Electroconvulsive Shock Therapy (ECT) * Judged to be at serious suicidal risk
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change in the Montgomery-Asberg Depression Rating Scale (MADRS) Total Score From Baseline to the End of 8 Weeks of Therapy. | 8 weeks | The Montgomery Asberg Depression Rating Scale measures symptoms of depression (MADRS) is a semi-structured interview rating scale for depression that assesses 10 symptoms. The scale is composed of 10 questions with a fixed 7 point scale (0-6). Total score ranges from 0-60. A higher score indicates more depressive symptoms. MADRS Response will be defined as a \> 50% reduction in MADRS score from baseline. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Active Treatment Group Riluzole: Initially dispensed 50 mg capsules to take BID. At two weeks, increase dose to 50 mg/100 mg. At four weeks increase to 100 mg BID (two capsules qAM, two capsules qHS). If significant side effects occur (at any time), titration can be slowed and doses can be reduced to a minimum daily dose of 50 mg/day, after which titration may resume by no more than 50 mg a week. Subjects who are unable to tolerate the minimal daily dose permitted in the study will be discontinued from further participation. In addition, if clinical remission is observed at a lower dose of study medication (defined as MADRS \< 12) the dose will not be increased further unless clinical symptoms recur. | 47 |
| Inactive/Placebo Group Placebo: Initially dispensed 50mg capsules to take BID. At two weeks increase dose to 50 mg/100 mg. At four weeks increase to 100 mg BID (two capsules qAM, two capsules qHS). If significant side effects occur (at any time), titration can be slowed and doses can be reduced to a minimum daily dose of 50 mg/day, after which titration may resume by no more than 50 mg a week. Subjects who are unable to tolerate the minimal daily dose permitted in the study will be discontinued from further participation. In addition, if clinical remission is observed at a lower dose of study medication (defined as MADRS \< 12) the dose will not be increased further unless clinical symptoms recur. | 47 |
| Total | 94 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 7 | 10 |
| Overall Study | Withdrawal by Subject | 3 | 2 |
Baseline characteristics
| Characteristic | Active Treatment Group | Total | Inactive/Placebo Group |
|---|---|---|---|
| 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 | 47 Participants | 94 Participants | 47 Participants |
| Age, Continuous | 43 years STANDARD_DEVIATION 10 | 43 years STANDARD_DEVIATION 10 | 43 years STANDARD_DEVIATION 11 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants | 4 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 43 Participants | 89 Participants | 46 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 0 Participants |
| Montgomery Asberg Depression Rating scale (MADRS) | 32.4 units on a scale STANDARD_DEVIATION 6.7 | 31.4 units on a scale STANDARD_DEVIATION 6.4 | 30.4 units on a scale STANDARD_DEVIATION 6 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 10 Participants | 20 Participants | 10 Participants |
| Race (NIH/OMB) More than one race | 3 Participants | 4 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 33 Participants | 69 Participants | 36 Participants |
| Region of Enrollment United States | 47 participants | 94 participants | 47 participants |
| Sex: Female, Male Female | 27 Participants | 55 Participants | 28 Participants |
| Sex: Female, Male Male | 20 Participants | 39 Participants | 19 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 47 | 0 / 47 |
| serious Total, serious adverse events | 0 / 47 | 0 / 47 |
Outcome results
Primary
Mean Change in the Montgomery-Asberg Depression Rating Scale (MADRS) Total Score From Baseline to the End of 8 Weeks of Therapy.
The Montgomery Asberg Depression Rating Scale measures symptoms of depression (MADRS) is a semi-structured interview rating scale for depression that assesses 10 symptoms. The scale is composed of 10 questions with a fixed 7 point scale (0-6). Total score ranges from 0-60. A higher score indicates more depressive symptoms. MADRS Response will be defined as a \> 50% reduction in MADRS score from baseline.
Time frame: 8 weeks
Population: Discrepancies in number of participants analyzed are due to subjects who dropped out and did not have final assessments. Imputed data was used for those participants.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Active Treatment Group | Mean Change in the Montgomery-Asberg Depression Rating Scale (MADRS) Total Score From Baseline to the End of 8 Weeks of Therapy. | Baseline MADRS | 32.4 units on a scale | Standard Deviation 1 |
| Active Treatment Group | Mean Change in the Montgomery-Asberg Depression Rating Scale (MADRS) Total Score From Baseline to the End of 8 Weeks of Therapy. | Week 8 | 21.7 units on a scale | Standard Deviation 1.8 |
| Inactive/Placebo Group | Mean Change in the Montgomery-Asberg Depression Rating Scale (MADRS) Total Score From Baseline to the End of 8 Weeks of Therapy. | Week 8 | 19.0 units on a scale | Standard Deviation 2 |
| Inactive/Placebo Group | Mean Change in the Montgomery-Asberg Depression Rating Scale (MADRS) Total Score From Baseline to the End of 8 Weeks of Therapy. | Baseline MADRS | 30.4 units on a scale | Standard Deviation 0.9 |