A Trial of SAMe for Treatment-Resistant Bipolar Depression - Full Text View

Purpose

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	Intervention
Bipolar Disorder Depression Bipolar Depression	Drug: SAMe Drug: Placebo


Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, 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

Resource links provided by NLM:

MedlinePlus related topics: Bipolar Disorder

Drug Information available for: Methionine

U.S. FDA Resources

Further study details as provided by Mclean Hospital:

Primary Outcome Measures:

MADRS [ Time Frame: At each weekly visit for 4 weeks ] [ Designated as safety issue: No ]
Assessment of current mania symptoms using Mania Acute Change Scale (MACS). All 20 questions on the scale have a 0 (absent)-4(most severe) range for describing mania symptoms. The mean MACS score totals were reported, with the total ranging from 0-80. 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:

HAM-D [ Time Frame: 6-weeks ] [ Designated as safety issue: No ]
YMRS [ Time Frame: 6-weeks ] [ Designated as safety issue: No ]


Enrollment:	17
Study Start Date:	September 2008
Study Completion Date:	September 2011
Primary Completion Date:	September 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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

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.

Eligibility


Ages Eligible for Study:	18 Years to 65 Years (Adult)
Genders Eligible for Study:	Both
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

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00762268

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 This link exits the ClinicalTrials.gov site

Publications:

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 History of Changes
Other Study ID Numbers:	2008-P-000276
Study First Received:	September 26, 2008
Results First Received:	June 17, 2014
Last Updated:	August 25, 2014
Health Authority:	United States: Food and Drug Administration

Keywords provided by 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

ClinicalTrials.gov processed this record on September 28, 2016