1. SAMe S-adenosylmethionine for Depression and Neuroprotection
Richard P. Brown MD
Associate Professor of Clinical Psychiatry
Columbia University College of Physicians and Surgeons

2. Presenter Disclosures
Richard P. Brown, MD
The following personal financial relationships with commercial interests relevant to this presentation existed during the past 12 months:
No relationships to disclose.

3. “You’ve been fooling around with
alternative medicines, haven’t you?”

4. SAMe physiological compound ranks with ATP as pivotal molecule SAMe: distributed all tissues and fluids of the body and fundamental to > 100 biochemical reactions (Adapted from Peter W Billigman)

5. Metabolism of SAMe Methylation Amino-propylation SAM-e
Produces: Serotonin
Norepinephrine
Dopamine
DNA, proteins
Phospholipids x
Amino-propylation
x-CH3
SAM-e
Joint Health
SAH
deca-Sam-e
PPi
Putrescine
Spermidine
Trans-sulfuration
Spermidine
Spermine
ATP
MTA
Homocysteine
(Hcy)
Cystathionine
B12
Methionine
Cysteine
MTHF
(THF)
Terahydrofolate
sulfate
(S04)
Glutathione (GSH)
Major Antioxidant

6. SAMe Is an Effective Anti-Depressant
12/13 studies – SAMe improved depression significantly more than placebo (1 negative study had flawed procedures)
19 DBRCTs - SAMe improved depression significantly more than tricyclic antidepressants
Augmented effects of other antidepressants
Increased response and remission in 73 SSRI nonresponders
(Berlanga C, et al. 1992; Papakostas et al. Am J Psych 2010;167: )

7. What is the # 1 Misconception about SAMe?
Same increases homocysteine,
a risk factor associated with cardiovascular disease.
True False X

8. SAMe Does NOT Increase Homocysteine
Mayo Clinic DBRPC
52 healthy adults given placebo or SAMe (800mg/day) for 4 weeks
No significant change in plasma Homocysteine
(Thompson MA, et al Dietary supplement S-adenosyl-L-methionine (AdoMet) effects on plasma homocysteine levels in healthy subjects: a double-blind, placebo-controlled, randomized clinical trial. JACM 15(5): 523-9)

9. SAMe: Clinical Benefits
Endogenous depression
 augment response to Rx antidepressants
Depression in people with Parkinson's, fibromyalgia, rheumatoid arthritis, HIV
Improve liver function in hepatitis, cirrhosis
Cognitive function
Attention Deficit Disorder
Pain of fibromyalgia
Opiate and alcohol withdrawal

10. What is the # 2 Misconception about SAMe?
“People with Parkinson’s Disease should not take SAMe” True False X

11. This misconception stems from a study in which a solution of SAMe was injected into the ventricles in the brains of rats. The injection adversely affected the neurons resulting in tremors that were seen as similar to tremors in Parkinson’s disease (PD) .
Such an effect has never been reported when Same has been taken by mouth or intramuscularly.
In fact, SAMe is very beneficial in PD
L-Dopa, used to treat PD, depletes SAMe worsening depression and other symptoms

12. SAMe for Depression in Parkinson’s
12-wk DBRPC SAMe mg/d vs citalopram10-20 mg/d 17 men + 15 women
Baseline 12 weeks
HAMD-17 Motor Sxs HAMD-17 Motor Sxs
SAMe
Citalopram
Placebo
Both improved depression. SAMe also improved motor symptoms.
(Varanese S, Brown RP, Di Rocco A, et al. Safety and preliminary evaluation of SAM-e and escitalopram in treatment of depression associated with PD. Longone Medical Center, NYU. Poster presentation, 2010.)

13. Cognitive Function in Adults without Dementia
Nutritional Formula (NF) Folic acid 400mcg, B12 6mcg, Vit E 30 IU, SAMe 400mg, N-acetyl cysteine 600 mg, Acetyl-L-carnitine 500mg
Cognitive Function in Adults without Dementia
improved word recall in subjects <74 years old
Early-stage Alzheimer’s improved Neuropsychiatric Inventory (NPI) - aggression, motor performance. Dementia Rating Scale improved 31% - Conceptualization, construction, attention, initiation/perseveration
Moderate to Late Stage Alzheimer’s -Improved NPI and behavioral-psychiatric symptoms
(Chan A. et al. J Nutr Health Aging. 2010; Chan A. et al. Am J Alzheimer’s Disease & other Dementia. 2009; Remington R. et al. Am J Alzheimer’s Disease & other Dementia )

14. SAM-e Do Nots Do not break tablets or refrigerate
Do not break blister pack seals until ready to use
Do not use “bargain brands”

15. Mania in Bipolar Disorder SAMe Does NOT Cause
Possible Side Effects of SAMe: activation, mild anxiety, nausea, loose stools
Mania in Bipolar Disorder
SAMe Does NOT Cause
Weight gain
Sexual dysfunction
Loss of libido
Sedation
Mental clouding

16. Key References
Bottiglieri T. Folate, Vitamin B12 and S-adenosylmethionine. Psychiatric Clinics of North America. Mar (1):1-14.
Brown RP, Gerbarg PL, Muskin PR. How to Use Herbs, Nutrients, and Yoga in Mental Health Care. W.W. Norton & Company, New York
Brown RP and Gerbarg PL. Chapter 38. Complementary and Integrative Treatments in Brain Injury in Textbook of Traumatic Brain Injury, Second Edition, ed by Silver JM, McAllister TW, and Yudofsky SC, American Psychiatric Press, Inc. Washington, DC, Pp

17. Additional References
Chan A. et al. A vitamin/nutriceutical formulation improves memory and cognitive performance in community-dwelling adults without dementia.J Nutr Health Aging.2010;14(3):
Chan A. et al. Efficacy of a vitamin/nutriceutical formulation for early-stage Alzheimer’s: 1 year, open-label pilot study. Am J Alzheimer’s Disease & other Dementia. 2009;23(6):
Remington R. et al. Efficacy of a vitamin/nutriceutical formulation for moderate-stage to later-stage Alzheimer’s: Placebo-controlled pilot study. Am J Alzheimer’s Disease & other Dementia.2009;24(1):