A Trial of SAMe for Treatment-Resistant Bipolar Depression

• ClinicalTrials.gov Identifier: NCT00762268
• Recruitment Status: Completed
• First Posted: September 30, 2008
• Results First Posted: August 26, 2014
• Last Update Posted: February 26, 2019
• Sponsor: Mclean Hospital
• Collaborator: Stanley Medical Research Institute
• Information provided by (Responsible Party): Beth L. Murphy MD, PhD, Mclean Hospital

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Bipolar Disorder; Depression; Bipolar Depression	Drug: SAMe; Drug: Placebo	Not Applicable

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 23 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: 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
• Study Start Date: September 2008
• Actual Primary Completion Date: September 2011
• Actual Study Completion Date: September 2011

Arms and Interventions

Arm	Intervention/treatment
Experimental: 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.	Drug: 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.; Other Name: S-adenosyl-L-methionine
Placebo Comparator: 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.	Drug: Placebo

Outcome Measures

Primary Outcome Measures :

1. Montgomery-Asberg Depression Scale (MADRS) [ Time Frame: 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 Outcome Measures :

1. Hamilton Rating Scale for Depression [ Time Frame: 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.
2. Young Mania Rating Scale [ Time Frame: 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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 65 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Locations

United States, Massachusetts

McLean Hospital

Belmont, Massachusetts, United States, 02478

Sponsors and Collaborators

Mclean Hospital

Stanley Medical Research Institute

Investigators

• Principal Investigator: Beth L Murphy, MD, PhD; Mclean Hospital

More Information

Additional Information:

link to hospital web site with clinical trials information 

Publications of Results:

Murphy BL, Babb SM, Ravichandran C, Cohen BM. Oral SAMe in persistent treatment-refractory bipolar depression: a double-blind, randomized clinical trial. J Clin Psychopharmacol. 2014 Jun;34(3):413-6. doi: 10.1097/JCP.0000000000000064.

• Responsible Party: Beth L. Murphy MD, PhD, Principal Investigator, Mclean Hospital
• ClinicalTrials.gov Identifier: NCT00762268
• Other Study ID Numbers: 2008-P-000276
• First Posted: September 30, 2008
• Results First Posted: August 26, 2014
• Last Update Posted: February 26, 2019
• Last Verified: February 2019

Keywords provided by Beth L. Murphy MD, PhD, Mclean Hospital:

SAMe; alternative treatments; bipolar disorder; depression; bipolar depression; treatment-resistant depression

Additional relevant MeSH terms:

Depression; Depressive Disorder; Bipolar Disorder; Behavioral Symptoms; Mood Disorders; Mental Disorders; Bipolar and Related Disorders