Depression, Parkinson's Disease
Conditions
Keywords
Parkinsons Disease, Depression, SAM-e
Brief summary
This study will test a chemical called s-adenosyl-methionine (SAM-e) for the treatment of depression in patients with Parkinson's disease (PD).
Detailed description
PD is commonly associated with depression, but conventional antidepressants have limited efficacy in patients with PD and may exacerbate motor symptoms. SAM-e is available in the United States as a food supplement and is promoted as a mood enhancer. SAM-e improves dopamine transmission, may have a beneficial effect on dopamine receptors, and may be a good alternative to the currently-used antidepressants in patients with PD. This study will investigate whether SAM-e is safe and effective in the treatment of depression associated with PD. The efficacy of SAM-e will be compared to placebo and to escitalopram, a selective serotonin reuptake inhibitor commonly used for the treatment of depression in PD. Participants in this study will be randomly assigned to receive SAM-e, escitalopram, or placebo for 12 weeks. Some participants may choose to extend treatment for an additional 12 weeks (for a total of 24 weeks on study medication). Participants will have study visits at entry and Weeks 2, 4, 8, and 12. Study visits will include neurological evaluation, psychiatric evaluation, blood tests, and quality of life questionnaires. A telephone interview will be conducted at Week 10.
Interventions
DRUGSAM-e
oral SAM-e in two divided doses, 1200mg or 1800mg daily, with placebo escitalopram.
DRUGoral escitalopram
20mg or 30mg daily in two divided doses, along with placebo SAM-e.
DRUGplacebo
oral placebo escitalopram and oral placebo SAM-e daily in two divided doses.
Sponsors
National Center for Complementary and Integrative Health (NCCIH)
Office of Dietary Supplements (ODS)
NYU Langone Health
Study design
Allocation
RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
30 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Idiopathic Parkinson's disease as indicated by the presence of at least two of the following signs: resting tremor, rigidity, bradykinesia, or postural reflex impairment * Stable anti-parkinson medication regimen, with no change in medications in the 4 weeks prior to study entry * No antidepressant or antipsychotic medications within 30 days prior to study entry * Agree not to start other pharmacotherapy, psychotherapy, or behavior therapy while participating in the trial * Acceptable methods of contraception * Ability to read and/or follow written and oral instructions presented in English * Sufficient cognitive ability (baseline Mini-Mental Status \> 24) to provide informed consent
Exclusion criteria
* History of cardiac, hepatic, renal, hematologic, respiratory, endocrine, vascular, metabolic, or other systems abnormalities that are clinically relevant in the opinion of study officials * Certain abnormal laboratory values * Pregnant or breastfeeding * Use of an investigational drug within 3 months of study entry * Use of St. John's Wort or any other natural product known to have mood enhancing properties in the 30 days prior to study entry * Selegiline or other monoamine oxidase inhibitor within the 6 weeks prior to study entry * Regular usage of anti-anxiety medications or habitual use of sleep medications, although occasional use of certain hypnotics (temazepam, melatonin, or zolpidem) is allowed * Psychotherapy initiated in the 6 months prior to study entry * History of bipolar disorder, hypomania, mania, schizophrenia, or other psychotic disorder * Serious suicidal attempt in the 12 months prior to study entry or serious suicidal tendencies/potential * Use of dopamine receptor antagonist (metoclopramide, haloperidol) * Secondary Parkinsonian symptoms due to drugs (including dopamine receptor antagonists), metabolic disorders, cerebrovascular disease, encephalitis, or other degenerative diseases
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Hamilton Depression Scale | 12 weeks | very severe, \>23/29; severe, 19-22/29; moderate, 14-18/29; mild, 8-13/29; and no depression, 0-7/29 (Hamilton M., J Neurol Neurosurg Psychiatry. 1960 Feb;23:56-62.) |
Countries
United States
Participant flow
Recruitment details
The recruitment dates 01NOV2006-31OCT2008 locations: James Godbold, PH.D. Mount Sinai School of Medicine Steven Ferrando, MD - Weill Medical College of Cornell University Teodoro Bottiglieri, Ph.D. - Baylor College of Medicine Dr. Peter Werner - Albert Einstein College of Medicine
Participants by arm
| Arm | Count |
|---|---|
| SAM-e oral SAM-e, 1200mg or 2400 mg | 12 |
| Escitalopram oral Escitalopram 10mg or 20m | 11 |
| Placebo Comparator oral placebo Escitalopram and placebo SAM-e | 6 |
| Total | 29 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 10 | 8 | 4 |
Baseline characteristics
| Characteristic | SAM-e | Escitalopram | Placebo Comparator | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 6 Participants | 8 Participants | 6 Participants | 20 Participants |
| Age, Categorical Between 18 and 65 years | 6 Participants | 3 Participants | 0 Participants | 9 Participants |
| Region of Enrollment United States | 12 participants | 11 participants | 6 participants | 29 participants |
| Sex: Female, Male Female | 6 Participants | 5 Participants | 3 Participants | 14 Participants |
| Sex: Female, Male Male | 6 Participants | 6 Participants | 3 Participants | 15 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 12 / 12 | 8 / 11 | 6 / 6 |
| serious Total, serious adverse events | 1 / 12 | 0 / 11 | 3 / 6 |
Outcome results
Primary
Change in Hamilton Depression Scale
very severe, \>23/29; severe, 19-22/29; moderate, 14-18/29; mild, 8-13/29; and no depression, 0-7/29 (Hamilton M., J Neurol Neurosurg Psychiatry. 1960 Feb;23:56-62.)
Time frame: 12 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SAM-e | Change in Hamilton Depression Scale | Baseline Visit Measurement | 17 units on a scale | Standard Deviation 4.8 |
| SAM-e | Change in Hamilton Depression Scale | Week 12 Measurement | 11.4 units on a scale | Standard Deviation 7.3 |
| Escitalopram | Change in Hamilton Depression Scale | Baseline Visit Measurement | 17.5 units on a scale | Standard Deviation 5.4 |
| Escitalopram | Change in Hamilton Depression Scale | Week 12 Measurement | 5.3 units on a scale | Standard Deviation 3.3 |
| Placebo Comparator | Change in Hamilton Depression Scale | Baseline Visit Measurement | 20.7 units on a scale | Standard Deviation 3.2 |
| Placebo Comparator | Change in Hamilton Depression Scale | Week 12 Measurement | 16.2 units on a scale | Standard Deviation 3.6 |