Trial Outcomes & Findings for Riluzole to Treat Depression in Bipolar Disorder (NCT NCT00054704)

Last Updated: 2019-04-25

Results Overview

The Montgomery-Asberg Depression Rating Scale (MADRS) is a clinician-rated assessment of depression symptoms. Patients were rated weekly on 10 symptoms on a scale of 0 to 6 for each item, where 0 indicated no symptoms and 6 indicated the highest severity of that symptom. Total scores range from 0 to 60, where a moderate severity of depression would be present with a score of at least 20.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

19 participants

Primary outcome timeframe

8 weeks

Results posted on

2019-04-25

Participant Flow

Participant milestones

Participant milestones
Measure	Riluzole Riluzole was dispensed either once or twice a day as 50 mg tablets. Riluzole dosing began at 50 mg twice per day by mouth and was increased on a weekly basis by 50 mg, as tolerated, to achieve a dose of 200 mg/day. Dose escalations continued until at least a 50% reduction in depression (MADRS) scores, intolerable side effects, or study completion. Dose was raised on a weekly basis by 50 mg until the dose of 200 mg was achieved unless precluded by an adverse event. If significant side effects occurred, titration was slowed and doses were reduced under double-blind conditions. The maximum permitted dose of riluzole was 200 mg/day. Those subjects not tolerating a dosage of 50 mg/day were removed from the study.	Placebo Placebo pills resembling 50 mg riluzole tables were dispensed either once or twice a day. Dosing began at 50 mg twice per day by mouth and was increased on a weekly basis by 50 mg, as tolerated, to achieve a dose of 200 mg/day. Dose escalations continued until at least a 50% reduction in depression (MADRS) scores, intolerable side effects, or study completion. Dose was raised on a weekly basis by 50 mg until the dose of 200 mg was achieved unless precluded by an adverse event. If significant side effects occurred, titration was slowed and doses were reduced under double-blind conditions. The maximum permitted dose of riluzole was 200 mg/day. Those subjects not tolerating a dosage of 50 mg/day were removed from the study.
Overall Study STARTED	8	11
Overall Study COMPLETED	3	6
Overall Study NOT COMPLETED	5	5

Reasons for withdrawal

Reasons for withdrawal
Measure	Riluzole Riluzole was dispensed either once or twice a day as 50 mg tablets. Riluzole dosing began at 50 mg twice per day by mouth and was increased on a weekly basis by 50 mg, as tolerated, to achieve a dose of 200 mg/day. Dose escalations continued until at least a 50% reduction in depression (MADRS) scores, intolerable side effects, or study completion. Dose was raised on a weekly basis by 50 mg until the dose of 200 mg was achieved unless precluded by an adverse event. If significant side effects occurred, titration was slowed and doses were reduced under double-blind conditions. The maximum permitted dose of riluzole was 200 mg/day. Those subjects not tolerating a dosage of 50 mg/day were removed from the study.	Placebo Placebo pills resembling 50 mg riluzole tables were dispensed either once or twice a day. Dosing began at 50 mg twice per day by mouth and was increased on a weekly basis by 50 mg, as tolerated, to achieve a dose of 200 mg/day. Dose escalations continued until at least a 50% reduction in depression (MADRS) scores, intolerable side effects, or study completion. Dose was raised on a weekly basis by 50 mg until the dose of 200 mg was achieved unless precluded by an adverse event. If significant side effects occurred, titration was slowed and doses were reduced under double-blind conditions. The maximum permitted dose of riluzole was 200 mg/day. Those subjects not tolerating a dosage of 50 mg/day were removed from the study.
Overall Study Lack of Efficacy	2	3
Overall Study Adverse Event	3	1
Overall Study Lost to Follow-up	0	1

Baseline Characteristics

Riluzole to Treat Depression in Bipolar Disorder

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Riluzole n=8 Participants Riluzole was dispensed either once or twice a day as 50 mg tablets. Riluzole dosing began at 50 mg twice per day by mouth and was increased on a weekly basis by 50 mg, as tolerated, to achieve a dose of 200 mg/day. Dose escalations continued until at least a 50% reduction in depression (MADRS) scores, intolerable side effects, or study completion. Dose was raised on a weekly basis by 50 mg until the dose of 200 mg was achieved unless precluded by an adverse event. If significant side effects occurred, titration was slowed and doses were reduced under double-blind conditions. The maximum permitted dose of riluzole was be 200 mg/day. Those subjects not tolerating a dosage of 50 mg/day were removed from the study.	Placebo n=11 Participants Placebo pills resembling 50 mg riluzole tables were dispensed either once or twice a day. Dosing began at 50 mg twice per day by mouth and was increased on a weekly basis by 50 mg, as tolerated, to achieve a dose of 200 mg/day. Dose escalations continued until at least a 50% reduction in depression (MADRS) scores, intolerable side effects, or study completion. Dose was raised on a weekly basis by 50 mg until the dose of 200 mg was achieved unless precluded by an adverse event. If significant side effects occurred, titration was slowed and doses were reduced under double-blind conditions. The maximum permitted dose of riluzole was be 200 mg/day. Those subjects not tolerating a dosage of 50 mg/day were removed from the study.	Total n=19 Participants Total of all reporting groups
Age, Continuous	47.29 Years STANDARD_DEVIATION 15.00 • n=93 Participants	48.73 Years STANDARD_DEVIATION 11.29 • n=4 Participants	48.08 Years STANDARD_DEVIATION 12.74 • n=27 Participants
Sex: Female, Male Female	1 Participants n=93 Participants	5 Participants n=4 Participants	6 Participants n=27 Participants
Sex: Female, Male Male	7 Participants n=93 Participants	6 Participants n=4 Participants	13 Participants n=27 Participants
Region of Enrollment United States	8 Participants n=93 Participants	11 Participants n=4 Participants	19 Participants n=27 Participants

PRIMARY outcome

Timeframe: 8 weeks

Population: Data from all patients were included in the analysis, except for one riluzole patient with missing data.

Outcome measures

Outcome measures
Measure	Riluzole n=8 Participants Riluzole was dispensed either once or twice a day as 50 mg tablets. Riluzole dosing began at 50 mg twice per day by mouth and was increased on a weekly basis by 50 mg, as tolerated, to achieve a dose of 200 mg/day. Dose escalations continued until at least a 50% reduction in depression (MADRS) scores, intolerable side effects, or study completion. Dose was raised on a weekly basis by 50 mg until the dose of 200 mg was achieved unless precluded by an adverse event. If significant side effects occurred, titration was slowed and doses were reduced under double-blind conditions. The maximum permitted dose of riluzole was be 200 mg/day. Those subjects not tolerating a dosage of 50 mg/day were removed from the study.	Placebo n=11 Participants Placebo pills resembling 50 mg riluzole tables were dispensed either once or twice a day. Dosing began at 50 mg twice per day by mouth and was increased on a weekly basis by 50 mg, as tolerated, to achieve a dose of 200 mg/day. Dose escalations continued until at least a 50% reduction in depression (MADRS) scores, intolerable side effects, or study completion. Dose was raised on a weekly basis by 50 mg until the dose of 200 mg was achieved unless precluded by an adverse event. If significant side effects occurred, titration was slowed and doses were reduced under double-blind conditions. The maximum permitted dose of riluzole was be 200 mg/day. Those subjects not tolerating a dosage of 50 mg/day were removed from the study.
Montgomery-Asberg Depression Rating Scale	29.551 Units on a scale Standard Error 2.481	23.723 Units on a scale Standard Error 1.916

Adverse Events

Riluzole

Serious events: 0 serious events

Other events: 7 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 8 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Riluzole n=8 participants at risk Riluzole was dispensed either once or twice a day as 50 mg tablets. Riluzole dosing began at 50 mg twice per day by mouth and was increased on a weekly basis by 50 mg, as tolerated, to achieve a dose of 200 mg/day. Dose escalations continued until at least a 50% reduction in depression (MADRS) scores, intolerable side effects, or study completion. Dose was raised on a weekly basis by 50 mg until the dose of 200 mg was achieved unless precluded by an adverse event. If significant side effects occurred, titration was slowed and doses were reduced under double-blind conditions. The maximum permitted dose of riluzole was be 200 mg/day. Those subjects not tolerating a dosage of 50 mg/day were removed from the study.	Placebo n=11 participants at risk Placebo pills resembling 50 mg riluzole tables were dispensed either once or twice a day. Dosing began at 50 mg twice per day by mouth and was increased on a weekly basis by 50 mg, as tolerated, to achieve a dose of 200 mg/day. Dose escalations continued until at least a 50% reduction in depression (MADRS) scores, intolerable side effects, or study completion. Dose was raised on a weekly basis by 50 mg until the dose of 200 mg was achieved unless precluded by an adverse event. If significant side effects occurred, titration was slowed and doses were reduced under double-blind conditions. The maximum permitted dose of riluzole was be 200 mg/day. Those subjects not tolerating a dosage of 50 mg/day were removed from the study.
Respiratory, thoracic and mediastinal disorders Coughing	12.5% 1/8 • Number of events 1 • Adverse event data was collected systematically on a weekly basis throughout the course of 8 weeks of study. An inventory of individual symptoms was used to evaluate adverse events on a scale from none to severe.	27.3% 3/11 • Number of events 3 • Adverse event data was collected systematically on a weekly basis throughout the course of 8 weeks of study. An inventory of individual symptoms was used to evaluate adverse events on a scale from none to severe.
Gastrointestinal disorders Gastrointestinal Problems	62.5% 5/8 • Number of events 5 • Adverse event data was collected systematically on a weekly basis throughout the course of 8 weeks of study. An inventory of individual symptoms was used to evaluate adverse events on a scale from none to severe.	9.1% 1/11 • Number of events 1 • Adverse event data was collected systematically on a weekly basis throughout the course of 8 weeks of study. An inventory of individual symptoms was used to evaluate adverse events on a scale from none to severe.
Reproductive system and breast disorders Decreased libido	25.0% 2/8 • Number of events 2 • Adverse event data was collected systematically on a weekly basis throughout the course of 8 weeks of study. An inventory of individual symptoms was used to evaluate adverse events on a scale from none to severe.	27.3% 3/11 • Number of events 3 • Adverse event data was collected systematically on a weekly basis throughout the course of 8 weeks of study. An inventory of individual symptoms was used to evaluate adverse events on a scale from none to severe.
General disorders Dizziness	37.5% 3/8 • Number of events 3 • Adverse event data was collected systematically on a weekly basis throughout the course of 8 weeks of study. An inventory of individual symptoms was used to evaluate adverse events on a scale from none to severe.	0.00% 0/11 • Adverse event data was collected systematically on a weekly basis throughout the course of 8 weeks of study. An inventory of individual symptoms was used to evaluate adverse events on a scale from none to severe.
General disorders Headache	12.5% 1/8 • Number of events 1 • Adverse event data was collected systematically on a weekly basis throughout the course of 8 weeks of study. An inventory of individual symptoms was used to evaluate adverse events on a scale from none to severe.	18.2% 2/11 • Number of events 2 • Adverse event data was collected systematically on a weekly basis throughout the course of 8 weeks of study. An inventory of individual symptoms was used to evaluate adverse events on a scale from none to severe.
General disorders Dry mouth	12.5% 1/8 • Number of events 1 • Adverse event data was collected systematically on a weekly basis throughout the course of 8 weeks of study. An inventory of individual symptoms was used to evaluate adverse events on a scale from none to severe.	9.1% 1/11 • Number of events 1 • Adverse event data was collected systematically on a weekly basis throughout the course of 8 weeks of study. An inventory of individual symptoms was used to evaluate adverse events on a scale from none to severe.
Musculoskeletal and connective tissue disorders Muscle, joint, or bone pain	25.0% 2/8 • Number of events 2 • Adverse event data was collected systematically on a weekly basis throughout the course of 8 weeks of study. An inventory of individual symptoms was used to evaluate adverse events on a scale from none to severe.	9.1% 1/11 • Number of events 1 • Adverse event data was collected systematically on a weekly basis throughout the course of 8 weeks of study. An inventory of individual symptoms was used to evaluate adverse events on a scale from none to severe.
Respiratory, thoracic and mediastinal disorders Nasal and throat problems	37.5% 3/8 • Number of events 3 • Adverse event data was collected systematically on a weekly basis throughout the course of 8 weeks of study. An inventory of individual symptoms was used to evaluate adverse events on a scale from none to severe.	27.3% 3/11 • Number of events 3 • Adverse event data was collected systematically on a weekly basis throughout the course of 8 weeks of study. An inventory of individual symptoms was used to evaluate adverse events on a scale from none to severe.
General disorders Sleep problems	62.5% 5/8 • Number of events 5 • Adverse event data was collected systematically on a weekly basis throughout the course of 8 weeks of study. An inventory of individual symptoms was used to evaluate adverse events on a scale from none to severe.	36.4% 4/11 • Number of events 4 • Adverse event data was collected systematically on a weekly basis throughout the course of 8 weeks of study. An inventory of individual symptoms was used to evaluate adverse events on a scale from none to severe.
General disorders Memory problems	25.0% 2/8 • Number of events 2 • Adverse event data was collected systematically on a weekly basis throughout the course of 8 weeks of study. An inventory of individual symptoms was used to evaluate adverse events on a scale from none to severe.	9.1% 1/11 • Number of events 1 • Adverse event data was collected systematically on a weekly basis throughout the course of 8 weeks of study. An inventory of individual symptoms was used to evaluate adverse events on a scale from none to severe.
Psychiatric disorders Suicidal ideation	25.0% 2/8 • Number of events 2 • Adverse event data was collected systematically on a weekly basis throughout the course of 8 weeks of study. An inventory of individual symptoms was used to evaluate adverse events on a scale from none to severe.	9.1% 1/11 • Number of events 1 • Adverse event data was collected systematically on a weekly basis throughout the course of 8 weeks of study. An inventory of individual symptoms was used to evaluate adverse events on a scale from none to severe.
General disorders Concentration difficulty	37.5% 3/8 • Number of events 3 • Adverse event data was collected systematically on a weekly basis throughout the course of 8 weeks of study. An inventory of individual symptoms was used to evaluate adverse events on a scale from none to severe.	18.2% 2/11 • Number of events 2 • Adverse event data was collected systematically on a weekly basis throughout the course of 8 weeks of study. An inventory of individual symptoms was used to evaluate adverse events on a scale from none to severe.
General disorders Fatigue	37.5% 3/8 • Number of events 3 • Adverse event data was collected systematically on a weekly basis throughout the course of 8 weeks of study. An inventory of individual symptoms was used to evaluate adverse events on a scale from none to severe.	18.2% 2/11 • Number of events 2 • Adverse event data was collected systematically on a weekly basis throughout the course of 8 weeks of study. An inventory of individual symptoms was used to evaluate adverse events on a scale from none to severe.
Skin and subcutaneous tissue disorders Skin irritation	12.5% 1/8 • Number of events 1 • Adverse event data was collected systematically on a weekly basis throughout the course of 8 weeks of study. An inventory of individual symptoms was used to evaluate adverse events on a scale from none to severe.	9.1% 1/11 • Number of events 1 • Adverse event data was collected systematically on a weekly basis throughout the course of 8 weeks of study. An inventory of individual symptoms was used to evaluate adverse events on a scale from none to severe.

Additional Information

Dr. Carlos Zarate

NIMH, DIRP, Experimental Therapeutics and Pathophysiology Branch

Phone: 3014510861

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place