A Trial of SAMe for Treatment-Resistant Bipolar Depression

February 25, 2019 updated by: Beth L. Murphy MD, PhD, Mclean Hospital

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

23

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Massachusetts
      • Belmont, Massachusetts, United States, 02478
        • McLean Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

14 years to 61 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / 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 Names:
  • 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

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Mclean Hospital

Collaborators

Stanley Medical Research Institute

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2008

Primary Completion (Actual)

September 1, 2011

Study Completion (Actual)

September 1, 2011

Study Registration Dates

First Submitted

September 26, 2008

First Submitted That Met QC Criteria

September 29, 2008

First Posted (Estimate)

September 30, 2008

Study Record Updates

Last Update Posted (Actual)

February 26, 2019

Last Update Submitted That Met QC Criteria

February 25, 2019

Last Verified

February 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2008-P-000276

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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