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

• Sponsor: Maurizio Fava, MD (Other)
• Overall Status: Completed
• CT.gov ID: NCT00101452
• Collaborator: National Center for Complementary and Integrative Health (NCCIH) (NIH)
• Enrollment: 199
• Locations: 2
• Arms: 3
• Duration (Months): 62
• Patients Per Site: 99.5
• Patients Per Site Per Month: 1.6

Study Details

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	N/A

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
• 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: Apr 1, 2005
• Actual Primary Completion Date: Jun 1, 2010
• Actual Study Completion Date: Jun 1, 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 Names: 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 Names: 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) [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

Criteria

• Ages Eligible for Study: 18 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

	Site	City	State	Country	Postal Code
1	Massachusetts General Hospital	Boston	Massachusetts	United States	02114
2	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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Maurizio Fava, MD, Director- Depression Clinical and Research Program, Massachusetts General Hospital
• ClinicalTrials.gov Identifier: NCT00101452
• Other Study ID Numbers: R01AT001638-01A1; R01AT001638-01A1
• First Posted: Jan 11, 2005
• Last Update Posted: Apr 4, 2017
• Last Verified: Mar 1, 2017

• Individual Participant Data (IPD) Sharing Statement: Undecided
• Plan to Share IPD: Undecided
• Keywords provided by Maurizio Fava, MD, Director- Depression Clinical and Research Program, Massachusetts General Hospital: Depression; Antidepressive Agents; Complementary Therapies
• Additional relevant MeSH terms: Depression; Depressive Disorder; Citalopram

Study Results

Participant Flow

Recruitment Details	Participants were recruited through general advertising at both the Depression Clinical and Research Program of MGH in Boston, MA and Butler Hospital in Providence, RI. Recruitment also took place at Family Doctors, LLC, in Swampscott, MA. We began recruiting participants in April 2005 and closed the study in December of 2009.
Pre-assignment Detail	Only five participants completed the allowed wash-out period prior to randomization. Participants screened at Day 0-7 and were asked to return for a baseline visit at Day 0. Subjects not randomized were excluded for being ineligible at the baseline or for being lost to follow-up between screen and baseline.

Arm/Group Title	1. SAMe	2. Escitalopram	3. Placebo
Arm/Group Description	Patients start with 1600mg/day for the first. If they do not feel better after 6 weeks, they may increase to 3200mg/day if their lab tests are normal.	Patients start with 10mg/day for the first 6 weeks. If they do not feel better after 6 weeks, they can increase to 20mg/day.	Placebo is a non-active treatment, sometimes called a sugar pill.
Period Title: Overall Study
STARTED	65	69	65
COMPLETED	21	26	22
NOT COMPLETED	44	43	43

Baseline Characteristics

Arm/Group Title	1. SAMe	2. Escitalopram	3. Placebo	Total
Arm/Group Description	a naturally occurring substance	A selective serotonin reuptake inhibitor (SSRI)	Sugar Pill- contains no active ingrediants	Total of all reporting groups
Overall Participants	59	55	52	166
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	56 94.9%	51 92.7%	50 96.2%	157 94.6%
>=65 years	3 5.1%	4 7.3%	2 3.8%	9 5.4%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	45.25 (13.98)	44.67 (14.29)	44.34 (15.19)	44.75 (14.43)
Sex: Female, Male (Count of Participants)
Female	32 54.2%	27 49.1%	27 51.9%	86 51.8%
Male	27 45.8%	28 50.9%	25 48.1%	80 48.2%
Region of Enrollment (participants) [Number]
United States	59 100%	55 100%	52 100%	166 100%

Outcome Measures

1. Primary Outcome

Title	Hamilton Rating Scale for Depression (HAM-D)
Description	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.
Time Frame	baseline and 24 weeks

Outcome Measure Data

Analysis Population Description

Based on having at least one post-baseline visit.

Arm/Group Title	1. SAMe	2. Escitalopram	3. Placebo
Arm/Group Description	a naturally occurring substance	A selective serotonin reuptake inhibitor (SSRI)	Sugar Pill- contains no active ingrediants
Measure Participants	59	55	52
Mean (Standard Deviation) [units on a scale]	-6.7 (7.3)	-7.5 (7.4)	-5.7 (7.0)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	1. SAMe, 2. Escitalopram, 3. Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.05
	Comments
	Method	ANOVA
	Comments

Adverse Events

Time Frame	Adverse events for SAMe, escitalopram, and placebo, were reported during the 12 week double blind course of the study and during the 12-week open cross over phase that followed the acute treatment phase.
Arm/Group Title	1. SAMe (Weeks 1-12)		2. Escitalopram (Weeks 1-12)		3. Placebo (Weeks 1-12)		4. SAMe (Weeks 12-24, Continuation)		5. Escitalopram (Weeks 12-24, Continuation)		6. Placebo (Weeks 12-24, Continuation)		7. SAMe Plus Escitalopram (Weeks 12-24, Cross-over)
Arm/Group Description	A naturally occurring substance (S-adenosyl methionine)		A selective serotonin reuptake inhibitor (SSRI)		Sugar Pill- contains no active ingredients		A naturally occurring substance (S-adenosyl methionine)		A selective serotonin reuptake inhibitor (SSRI)		Sugar Pill- contains no active ingredients		A naturally occurring substance (S-adenosyl methionine) plus a selective serotonin reuptake inhibitor (SSRI)
All Cause Mortality
	1. SAMe (Weeks 1-12)		2. Escitalopram (Weeks 1-12)		3. Placebo (Weeks 1-12)		4. SAMe (Weeks 12-24, Continuation)		5. Escitalopram (Weeks 12-24, Continuation)		6. Placebo (Weeks 12-24, Continuation)		7. SAMe Plus Escitalopram (Weeks 12-24, Cross-over)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/59 (0%)		0/55 (0%)		0/52 (0%)		0/17 (0%)		0/11 (0%)		0/15 (0%)		0/43 (0%)
Serious Adverse Events
	1. SAMe (Weeks 1-12)		2. Escitalopram (Weeks 1-12)		3. Placebo (Weeks 1-12)		4. SAMe (Weeks 12-24, Continuation)		5. Escitalopram (Weeks 12-24, Continuation)		6. Placebo (Weeks 12-24, Continuation)		7. SAMe Plus Escitalopram (Weeks 12-24, Cross-over)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/59 (0%)		0/55 (0%)		0/52 (0%)		0/17 (0%)		0/11 (0%)		0/15 (0%)		0/43 (0%)
Other (Not Including Serious) Adverse Events
	1. SAMe (Weeks 1-12)		2. Escitalopram (Weeks 1-12)		3. Placebo (Weeks 1-12)		4. SAMe (Weeks 12-24, Continuation)		5. Escitalopram (Weeks 12-24, Continuation)		6. Placebo (Weeks 12-24, Continuation)		7. SAMe Plus Escitalopram (Weeks 12-24, Cross-over)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	27/59 (45.8%)		32/55 (58.2%)		29/52 (55.8%)		14/17 (82.4%)		12/14 (85.7%)		12/15 (80%)		29/43 (67.4%)
Gastrointestinal disorders
Gastrointestinal	17/59 (28.8%)	17	19/55 (34.5%)	19	16/52 (30.8%)	16	11/17 (64.7%)	11	7/11 (63.6%)	7	7/15 (46.7%)	7	16/43 (37.2%)	16
General disorders
Somatic	3/59 (5.1%)	3	7/55 (12.7%)	7	5/52 (9.6%)	5	9/17 (52.9%)	9	9/11 (81.8%)	9	10/15 (66.7%)	10	15/43 (34.9%)	15
Psychiatric disorders
Psychiatric	2/59 (3.4%)	2	1/55 (1.8%)	1	3/52 (5.8%)	3	6/17 (35.3%)	6	5/11 (45.5%)	5	6/15 (40%)	6	5/43 (11.6%)	5
Reproductive system and breast disorders
Sexual dysfunction	5/59 (8.5%)	5	5/55 (9.1%)	5	5/52 (9.6%)	5	3/17 (17.6%)	3	3/11 (27.3%)	3	2/15 (13.3%)	2	7/40 (17.5%)	7

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.