Safety and Effectiveness of S-adenosyl-l-methionine (SAMe) for the Treatment of Major Depression

• ClinicalTrials.gov Identifier: NCT00101452
• Recruitment Status: Completed
• First Posted: January 11, 2005
• Results First Posted: December 31, 2012
• Last Update Posted: April 4, 2017
• Sponsor: Maurizio Fava, MD
• Collaborator: National Center for Complementary and Integrative Health (NCCIH)
• Information provided by (Responsible Party): Maurizio Fava, MD, Massachusetts General Hospital

Study Description

Brief Summary:

The purpose of this study is to determine the safety and effectiveness of s-adenosyl-l-methionine (SAMe) in treating major depression.

Condition or disease	Intervention/treatment	Phase
Depression	Drug: S-adenosyl-l-methionine; Drug: Escitalopram; Drug: Placebo	Not Applicable

Detailed Description:

SAMe is a substance that is naturally produced by the body and is also sold as an over-the-counter drug. Although SAMe has not yet been approved for treating depression, evidence suggests that it has antidepressant properties. This study will determine whether SAMe is safe and effective in treating major depression.

This study will last 24 weeks. Participants will be randomly assigned to receive either the antidepressant escitalopram, SAMe, or placebo for 12 weeks. Participants who respond to treatment at the end of 12 weeks will stay on their regimen for an additional 12 weeks. Participants who do not respond to treatment will enter an open treatment phase where they will receive SAMe and escitalopram for 12 more weeks. Depression scales and self-report questionnaires will be used to assess participants. All participants will receive 3 months of follow-up care, including free medication and clinic visits as necessary.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 199 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: A Double-Blind, Placebo-Controlled Study of the Alternative Therapy S-Adenosyl-L-Methionine (SAMe) vs Escitalopram in Major Depressive Disorder (MDD)
• Study Start Date: April 2005
• Actual Primary Completion Date: June 2010
• Actual Study Completion Date: June 2010

Arms and Interventions

Arm	Intervention/treatment
Experimental: S-adenosyl-l-methionine (SAMe); A natural substance	Drug: S-adenosyl-l-methionine; 1600 mg per day with possibility of increasing to 3200 mg per day at 6 weeks; Other Name: SAMe
Active Comparator: 2. Escitalopram; A selective serotonin reuptake inhibitor (SSRI)	Drug: Escitalopram; 10 mg per day, with possibility of increasing to 20 mg/day at 6 weeks; Other Name: Lexapro
Placebo Comparator: 3. placebo; Sugar pill- contains no active ingredients	Drug: Placebo; placebo capsules look like escitalopram capsules and SAMe capsules

Outcome Measures

Primary Outcome Measures :

1. Hamilton Rating Scale for Depression (HAM-D) [ Time Frame: baseline and 24 weeks ]
   The change in total HAM-D score between baseline and endpoint was the primary outcomes measure. This measure is a clinician rated inventory of depressive symptoms. All items are scored on a scale of zero to four and the sum of the scores provides the total score for the measure. Scores can range from 0- 68. On this scale, higher scores indicate poorer outcomes.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 80 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Diagnosis of major depression
• Score of 25 or higher on the Inventory of Depressive Symptomatology (IDS-C) scale
• Score of higher than 2 on the Clinical Global Impression Improvement (CGI) scale
• Willing to use acceptable methods of contraception

Exclusion Criteria:

• Suicidal or homicidal
• Unstable illness, including cardiovascular, hepatic, renal, respiratory, endocrine, neurological, or hematological disease.
• Any of the following mental conditions: organic mental disorders; schizophrenia; delusional disorder; psychotic disorders; bipolar disorder; recent bereavement; severe borderline or antisocial personality disorder; panic disorder; or obsessive compulsive disorder
• Substance abuse, including alcohol abuse, within 6 months prior to study entry
• Uncontrolled seizure disorder, or a seizure disorder controlled with psychotropic anticonvulsants
• Psychotic features
• Current use of other psychotropic drugs
• Hypothyroidism
• Have taken 6 weeks or more of either escitalopram or SAMe during the current depressive episode
• Previous intolerance of SAMe or escitalopram
• Investigational psychotropic drugs within 1 year prior to study entry
• Have received two or more antidepressant therapies of adequate doses and duration and failed to respond
• Have received depression-focused psychotherapy
• Bleeding tissue disorder, low platelet counts, a history of GI bleeding, or use of medications that alter bleeding risk
• Long-term aspirin use
• Pregnancy

Contacts and Locations

Locations

United States, Massachusetts

Massachusetts General Hospital

Boston, Massachusetts, United States, 02114

United States, Rhode Island

Butler Hospital

Providence, Rhode Island, United States, 02906

Sponsors and Collaborators

Maurizio Fava, MD

National Center for Complementary and Integrative Health (NCCIH)

Investigators

• Principal Investigator: Maurizio Fava, MD; Massachusetts General Hospital

More Information

Publications of Results:

Mischoulon D, Price LH, Carpenter LL, Tyrka AR, Papakostas GI, Baer L, Dording CM, Clain AJ, Durham K, Walker R, Ludington E, Fava M. A double-blind, randomized, placebo-controlled clinical trial of S-adenosyl-L-methionine (SAMe) versus escitalopram in major depressive disorder. J Clin Psychiatry. 2014 Apr;75(4):370-6. doi: 10.4088/JCP.13m08591.

Sarris J, Price LH, Carpenter LL, Tyrka AR, Ng CH, Papakostas GI, Jaeger A, Fava M, Mischoulon D. Is S-Adenosyl Methionine (SAMe) for Depression Only Effective in Males? A Re-Analysis of Data from a Randomized Clinical Trial. Pharmacopsychiatry. 2015 Jul;48(4-5):141-4. doi: 10.1055/s-0035-1549928. Epub 2015 May 26.

Mischoulon D, Price LH, Carpenter LL, Tyrka AR, Papakostas GI, Fava M. Dr. Mischoulon and colleagues reply. J Clin Psychiatry. 2014 Nov;75(11):e1328-9. doi: 10.4088/JCP.14lr09266a.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Laferton JAC, Vijapura S, Baer L, Clain AJ, Cooper A, Papakostas G, Price LH, Carpenter LL, Tyrka AR, Fava M, Mischoulon D. Mechanisms of Perceived Treatment Assignment and Subsequent Expectancy Effects in a Double Blind Placebo Controlled RCT of Major Depression. Front Psychiatry. 2018 Sep 7;9:424. doi: 10.3389/fpsyt.2018.00424. eCollection 2018.

Admon R, Nickerson LD, Dillon DG, Holmes AJ, Bogdan R, Kumar P, Dougherty DD, Iosifescu DV, Mischoulon D, Fava M, Pizzagalli DA. Dissociable cortico-striatal connectivity abnormalities in major depression in response to monetary gains and penalties. Psychol Med. 2015 Jan;45(1):121-31. doi: 10.1017/S0033291714001123. Epub 2014 May 15.

• Responsible Party: Maurizio Fava, MD, Director- Depression Clinical and Research Program, Massachusetts General Hospital
• ClinicalTrials.gov Identifier: NCT00101452
• Other Study ID Numbers: R01AT001638-01A1 ( U.S. NIH Grant/Contract ); R01AT001638-01A1 ( U.S. NIH Grant/Contract )
• First Posted: January 11, 2005
• Results First Posted: December 31, 2012
• Last Update Posted: April 4, 2017
• Last Verified: March 2017

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

Keywords provided by Maurizio Fava, MD, Massachusetts General Hospital:

Depression; Antidepressive Agents; Complementary Therapies

Additional relevant MeSH terms:

Depression; Depressive Disorder; Behavioral Symptoms; Mood Disorders; Mental Disorders; Citalopram; Serotonin Uptake Inhibitors; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Molecular Mechanisms of Pharmacological Action; Neurotransmitter Agents; Serotonin Agents; Physiological Effects of Drugs; Antidepressive Agents, Second-Generation; Antidepressive Agents; Psychotropic Drugs