Depression
Conditions
Keywords
Depression, Antidepressive Agents, Complementary Therapies
Brief summary
The purpose of this study is to determine the safety and effectiveness of s-adenosyl-l-methionine (SAMe) in treating major depression.
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.
Interventions
1600 mg per day with possibility of increasing to 3200 mg per day at 6 weeks
DRUGEscitalopram
10 mg per day, with possibility of increasing to 20 mg/day at 6 weeks
DRUGPlacebo
placebo capsules look like escitalopram capsules and SAMe capsules
Sponsors
National Center for Complementary and Integrative Health (NCCIH)
Maurizio Fava, MD
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
United States
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 details
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.
Participants by arm
| Arm | Count |
|---|---|
| 1. SAMe a naturally occurring substance | 59 |
| 2. Escitalopram A selective serotonin reuptake inhibitor (SSRI) | 55 |
| 3. Placebo Sugar Pill- contains no active ingrediants | 52 |
| Total | 166 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 2 | 0 | 1 |
| Overall Study | Baseline Fail | 2 | 1 | 2 |
| Overall Study | Lost to Follow-up | 13 | 8 | 14 |
| Overall Study | Other | 15 | 16 | 12 |
| Overall Study | Physician Decision | 0 | 3 | 2 |
| Overall Study | Protocol Violation | 2 | 1 | 3 |
| Overall Study | Withdrawal by Subject | 10 | 14 | 9 |
Baseline characteristics
| Characteristic | 2. Escitalopram | 3. Placebo | 1. SAMe | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 4 Participants | 2 Participants | 3 Participants | 9 Participants |
| Age, Categorical Between 18 and 65 years | 51 Participants | 50 Participants | 56 Participants | 157 Participants |
| Age, Continuous | 44.67 years STANDARD_DEVIATION 14.29 | 44.34 years STANDARD_DEVIATION 15.19 | 45.25 years STANDARD_DEVIATION 13.98 | 44.75 years STANDARD_DEVIATION 14.43 |
| Region of Enrollment United States | 55 participants | 52 participants | 59 participants | 166 participants |
| Sex: Female, Male Female | 27 Participants | 27 Participants | 32 Participants | 86 Participants |
| Sex: Female, Male Male | 28 Participants | 25 Participants | 27 Participants | 80 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk |
|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 59 | 0 / 55 | 0 / 52 | 0 / 17 | 0 / 11 | 0 / 15 | 0 / 43 |
| other Total, other adverse events | 27 / 59 | 32 / 55 | 29 / 52 | 14 / 17 | 12 / 14 | 12 / 15 | 29 / 43 |
| serious Total, serious adverse events | 0 / 59 | 0 / 55 | 0 / 52 | 0 / 17 | 0 / 11 | 0 / 15 | 0 / 43 |
Outcome results
Primary
Hamilton Rating Scale for Depression (HAM-D)
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
Population: Based on having at least one post-baseline visit.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 1. SAMe | Hamilton Rating Scale for Depression (HAM-D) | -6.7 units on a scale | Standard Deviation 7.3 |
| 2. Escitalopram | Hamilton Rating Scale for Depression (HAM-D) | -7.5 units on a scale | Standard Deviation 7.4 |
| 3. Placebo | Hamilton Rating Scale for Depression (HAM-D) | -5.7 units on a scale | Standard Deviation 7 |
p-value: <0.05ANOVA