A Trial of SAMe for Treatment-Resistant Bipolar Depression

Study Overview
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Brief Summary
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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
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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.

Official Title
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Intermittent-Dose Oral SAMe (S-adenosyl-L-methionine) in Persistent and Treatment-Refractory Bipolar Depression: A Double-Blind Pilot Trial With an Optional Open-label Follow-up

Conditions
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Bipolar Disorder, Depression, Bipolar Depression

Intervention / Treatment
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* Drug: SAMe
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SAMe<br>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. | Drug: SAMe<br>* 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.<br>* Other names: S-adenosyl-L-methionine;|
| Placebo Comparator: placebo<br>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. | Drug: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | At each weekly visit for 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 6-weeks | 
| 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. | 6-weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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SAMe, alternative treatments, bipolar disorder, depression, bipolar depression, treatment-resistant depression