This study will test a chemical called s-adenosyl-methionine (SAM-e) for the treatment of depression in patients with Parkinson's disease (PD).

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.

• Parkinson's Disease
• Depression

• Drug: SAM-e
• Drug: oral citalopram
• Drug: placebo

• Experimental: 40 subjects receiving oral SAM-e, 1200mg or 1800mg daily in two divided doses, and placebo citalopram.
• Active Comparator: 40 subjects receiving oral citalopram 20mg or 40 mg daily, in two divided doses, and placebo SAM-e.
• Placebo Comparator: 20 subjects receiving oral placebo citalopram and placebo SAM-3 daily in two divided doses.

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