Bipolar Depression, Bipolar Disorder, Depression
Conditions
Keywords
SAMe, alternative treatments, bipolar disorder, depression, bipolar depression, treatment-resistant depression
Brief summary
S-adenosyl-L-methionine (SAMe) is a dietary supplement with antidepressant properties. SAMe's mechanism of action remains unclear, but it appears to be distinct from that of conventional antidepressants. The purpose of this study is to examine the effect of these properties on the mood of bipolar subjects with persistent major depression that has been unresponsive to standard pharmacotherapy.
Detailed description
Depression in bipolar disorder is a significant source of disease-related debility; with bipolar individuals typically spending three fold as much time depressed as manic or hypomanic. Clinicians treating bipolar disorder often struggle to provide relief from depressive symptoms that are more often treatment resistant than in unipolar depression. To complicate matters further, the risk/benefit ratio of currently available antidepressants is a source of debate within the field of psychiatry. S-adenosyl-L-methionine (SAMe) is a dietary supplement with well-established antidepressant properties. SAMe's mechanism of action remains unclear, but it appears to be distinct from that of conventional antidepressants. The purpose of this study is to examine the effect of these properties on the mood of bipolar subjects with persistent major depression that has been unresponsive to standard pharmacotherapy. An unusual aspect of the current study design is the schedule of SAMe dosing. SAMe tablets will be administered intermittently and in steadily increasing dosages. The purpose of this gradual and intermittent dosage titration is to lessen the risk of antidepressant-induced mania by seeking the minimum effective oral dose of SAMe.
Interventions
DRUGSAMe
SAMe tablets will be administered intermittently and in steadily increasing dosages. Subjects will receive oral SAMe for only 3 days per week, followed by a 4 day rest-period, before the next dosage increase. SAMe dosage will be progressively increased each week to a maximum of 1600 mg per day over a 4-week period.
DRUGPlacebo
Sponsors
Stanley Medical Research Institute
Mclean Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* bipolar disorder * depressed for 3-12 months * mood unresponsive to at least 2 treatments * currently on mood stabilizer at therapeutic doses
Exclusion criteria
* history of mania while on adequate mood stabilizer * rapid cycling bipolar disorder * previous use of SAMe during current episode * unstable medical illness including parkinson's disease * methotrexate use * pregnancy * substance abuse/dependence
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Montgomery-Asberg Depression Scale (MADRS) | At each weekly visit for 4 weeks | Assessment of current depression symptoms using Montgomery-Asberg Depression Scale (MADRS). All 10 questions on the scale have a 0 (absent)-6(most severe) range for describing symptoms, with the total ranging from 0-60. A higher total score indicates a greater number of symptoms and higher symptom intensity, while a smaller score indicates a lesser number of symptoms and lower intensity. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Hamilton Rating Scale for Depression | 6-weeks | Rating scale of depression symptoms (range 0-50). A higher total score indicates a greater number of symptoms and higher symptom intensity, while a smaller score indicates a lesser number of symptoms and lower intensity. |
| Young Mania Rating Scale | 6-weeks | Rating scale for manic symptoms (range 0-60). A higher total score indicates a greater number of symptoms and higher symptom intensity, while a smaller score indicates a lesser number of symptoms and lower intensity. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| SAMe SAMe: SAMe tablets will be administered intermittently and in steadily increasing dosages. Subjects will receive oral SAMe for only 3 days per week, followed by a 4 day rest-period, before the next dosage increase. SAMe dosage will be progressively increased each week to a maximum of 1600 mg per day over a 4-week period. | 9 |
| Placebo Placebo: Placebo SAMe tablets will be administered intermittently and in steadily increasing dosages. Subjects will receive oral pills for only 3 days per week, followed by a 4 day rest-period, before the round. The apparent dosage will be progressively increased each week to mimic a maximum of 1600 mg per day over a 4-week period. | 8 |
| Total | 17 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 3 | 3 |
Baseline characteristics
| Characteristic | SAMe | Placebo | 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 | 9 Participants | 8 Participants | 17 Participants |
| Region of Enrollment United States | 9 participants | 8 participants | 17 participants |
| Sex: Female, Male Female | 5 Participants | 4 Participants | 9 Participants |
| Sex: Female, Male Male | 4 Participants | 4 Participants | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 1 / 9 | 0 / 8 |
| serious Total, serious adverse events | 0 / 9 | 0 / 8 |
Outcome results
Primary
Montgomery-Asberg Depression Scale (MADRS)
Assessment of current depression symptoms using Montgomery-Asberg Depression Scale (MADRS). All 10 questions on the scale have a 0 (absent)-6(most severe) range for describing symptoms, with the total ranging from 0-60. A higher total score indicates a greater number of symptoms and higher symptom intensity, while a smaller score indicates a lesser number of symptoms and lower intensity.
Time frame: At each weekly visit for 4 weeks
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| SAMe | Montgomery-Asberg Depression Scale (MADRS) | Week 1 | 24.7 units on a scale |
| SAMe | Montgomery-Asberg Depression Scale (MADRS) | Week 3 | 23.7 units on a scale |
| SAMe | Montgomery-Asberg Depression Scale (MADRS) | Week 2 | 26.3 units on a scale |
| SAMe | Montgomery-Asberg Depression Scale (MADRS) | Week 4 | 20.1 units on a scale |
| SAMe | Montgomery-Asberg Depression Scale (MADRS) | Baseline | 29.4 units on a scale |
| Placebo | Montgomery-Asberg Depression Scale (MADRS) | Week 4 | 18.1 units on a scale |
| Placebo | Montgomery-Asberg Depression Scale (MADRS) | Baseline | 28.3 units on a scale |
| Placebo | Montgomery-Asberg Depression Scale (MADRS) | Week 1 | 24.2 units on a scale |
| Placebo | Montgomery-Asberg Depression Scale (MADRS) | Week 2 | 23.0 units on a scale |
| Placebo | Montgomery-Asberg Depression Scale (MADRS) | Week 3 | 18.5 units on a scale |
p-value: 1Regression, Linear
Secondary
Hamilton Rating Scale for Depression
Rating scale of depression symptoms (range 0-50). A higher total score indicates a greater number of symptoms and higher symptom intensity, while a smaller score indicates a lesser number of symptoms and lower intensity.
Time frame: 6-weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| SAMe | Hamilton Rating Scale for Depression | 11.9 units on a scale | Standard Deviation 7.6 |
| Placebo | Hamilton Rating Scale for Depression | 7.3 units on a scale | Standard Deviation 0.9 |
Comparison: Change from intake scores.p-value: 0.05Chi-squared
Secondary
Young Mania Rating Scale
Rating scale for manic symptoms (range 0-60). A higher total score indicates a greater number of symptoms and higher symptom intensity, while a smaller score indicates a lesser number of symptoms and lower intensity.
Time frame: 6-weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| SAMe | Young Mania Rating Scale | 2.8 units on a scale | Standard Deviation 2 |
| Placebo | Young Mania Rating Scale | 1.8 units on a scale | Standard Deviation 0.5 |
p-value: 0.05Chi-squared