SAMeSAMeS-adenosylmethionine for S-adenosylmethionine for

Depression and NeuroprotectionDepression and Neuroprotection

Richard P. Brown MD

Associate Professor of Clinical Psychiatry

Columbia University College of Physicians and Surgeons

Presenter Disclosures

• The following personal financial relationships with commercial interests relevant to this presentation existed during the past 12 months:

• No relationships to disclose.

Richard P. Brown, MD

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

S y n th e s is o f S A M e

M e th io n in e

M e th io n in e -a d e n o s y l tra n s fe ra s e (M A T )

A d e n o s in e tr ip h o s p h a te(A T P )

S A M eN

N

N

N

N H2

O

O H

CH2 S

C H3

CH2

CH2

CH

C O O H

O H

N H2

+

C H 3

SAMephysiologicalcompound ranks withATPas pivotalmolecule

SAMe: distributed all tissues and fluids of the body and fundamental to > 100 biochemical reactions

(Adapted from Peter W Billigman)

Metabolism of SAMe

Methionine

SAM-e

SAH

Homocysteine (Hcy)

deca-Sam-e

MTA

MTHF (THF)Terahydrofolate

B12

ATP

PPiPutrescine

Spermidine

Spermidine

Spermine

xx-CH3

Cystathionine

Cysteine

Glutathione (GSH)Major Antioxidant

Amino-propylation

Methylation

Trans-sulfuration

sulfate(S04)

Produces: SerotoninNorepinephrineDopamineDNA, proteinsPhospholipids

Joint Health

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;167:942-948)

What is the # 1 Misconception about SAMe?

Same increases homocysteine,a risk factor associated with

cardiovascular disease.

True False

X

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. 2009. 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)

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

What is the # 2 Misconception about SAMe?

“People with Parkinson’s Disease should not take SAMe”

True False

X

• 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

SAMe for Depression in Parkinson’s12-wk DBRPC SAMe 1200-2400 mg/d vs

citalopram10-20 mg/d 17 men + 15 women

Baseline 12 weeks

HAMD-17 Motor Sxs HAMD-17 Motor Sxs

SAMe 18 25 11 15

Citalopram 18 24 8 26

Placebo 18 24 15 26

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.)

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 Dementiaimproved 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. 2009.)

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”

• Possible Side Effects of SAMe: activation, mild anxiety, nausea, loose stools

Mania in Bipolar Disorder

• SAMe Does NOT CauseWeight gain

Sexual dysfunction

Loss of libido

Sedation

Mental clouding

Key References• Bottiglieri T. Folate, Vitamin B12 and S-

adenosylmethionine. Psychiatric Clinics of North America. Mar 2013 36(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. 2009.

• 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, 2011. Pp. 599-622.

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):224-30.

• 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):571-589.

• 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):27- 33.