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Dietary supplement

Double Strength SAM-e 400 mg Ingredients & Drug Interactions

by Puritan's Pride

Double Strength SAM-e 400 mg label
See full label image
Other (e.g. Tea Bag) Category: Non-nutrient/non-botanical
Most serious interaction: Moderate
Clinical methodology reviewed by · Updated Sep 16, 2026 · Label data from the NIH DSLD
What is this page for?

First and foremost: checking Double Strength SAM-e 400 mg against your medications. The heart of this page is the interaction checker and the full interaction report — how this product’s ingredients may interact with prescription and over-the-counter medicines you may be taking.

Around that, we add a pharmacist’s high-level view of the product as a whole — what’s inside, the evidence for its stated use, how transparent the label is, and what safety data exists — so you can see the full picture in one place. It’s educational information from our licensed clinical databases and the clinical staff at HelloPharmacist — not medical advice — and we don’t sell or endorse products. Our editorial policy

The interaction bottom line Most serious interaction: Moderate

Double Strength SAM-e 400 mg is a dietary supplement by Puritan's Pride with 1 active ingredient. Its ingredients are commonly taken for depression, osteoarthritis joint pain, liver conditions.Based on those ingredients, 189 medications have a known interaction with it, the most serious rated moderate. The ingredients most likely to interact are S-Adenosylmethionine. Use the checker below to test your specific medication, or read the full HelloPharmacist Interaction Report.

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Check Your Meds Against Double Strength SAM-e 400 mg by Puritan's Pride

Ask about any prescription or over-the-counter medication and we check it for interactions with Double Strength SAM-e 400 mg by Puritan's Pride — and tell you which ingredient is responsible.

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HelloPharmacist Scorecard of Double Strength SAM-e 400 mg by Puritan's Pride

Our pharmacy team’s full take, with four database checks built into the cards below — a summary of what is known, not a grade of the product itself.

From our pharmacy team — supplement deep dive

Generated from HelloPharmacist’s pharmacist-curated databases and editorial rules · Last generated Jul 23, 2026

What’s inside

Full disclosure
Ingredient Transparency · database check
Full

Every active ingredient lists its own amount on the label.

Why this rating?
  • The label discloses an exact amount for 1 of its 1 active ingredient.
  • No proprietary blends here — you can verify the dose of every single component.

This product contains one active ingredient: S-Adenosylmethionine (SAMe), a compound your body naturally makes that plays a role in mood, joint health, and liver function. Each dose delivers 400 mg.

The remaining ingredients—vegetable cellulose and polymethacrylate—are inactive components that form the capsule.

Does it work?

Strong evidence
Evidence for Intended Use · database check
By FDA rules, dietary supplements can’t claim to treat, cure, or prevent disease — so labels speak in careful marketing language. We discern each product’s intended use from its name, label claims, and label statements, then grade the clinical evidence for that use. How these ratings are computed
Strong

Clinical evidence supports at least one of this product's ingredients for its stated purpose.

Why this rating?
  • The label markets this product for: supports mood and joint function.
  • We looked for evidence on: Depression, Fibromyalgia, Osteoarthritis, emotional well-being, joint comfort.
  • The strongest evidence on file: Same is rated "Likely Effective" for Osteoarthritis (Natural Medicines).
  • Also on file: Same is rated "Possibly Effective" for Depression.
  • Also on file: Same is rated "Insufficient Reliable Evidence To Rate" for Fibromyalgia.

SAMe is likely effective for osteoarthritis pain and stiffness. It's possibly effective for depression and for liver conditions involving bile flow problems (cholestasis).

For Alzheimer disease and ADHD, there isn't enough reliable evidence in our data to rate how well it works. If you're considering SAMe for any of these conditions, talk it over with your doctor to see if the evidence fits your situation.

The evidence, ingredient by ingredient Same

How safe is it?

Well-documented data
Safety Information · database check
Well characterized

Adverse-effect, pregnancy, and general safety data are on file for most of these ingredients.

Why this rating?
  • We hold adverse-effect (side-effect) data for 1 of the 1 matched ingredient.
  • Pregnancy & breastfeeding safety ratings cover 1 of 1.
  • General safety write-ups exist for 1 of 1.
  • Remember: this measures how much safety information exists. Thin data is not the same as being safe.

SAMe is generally well tolerated in typical doses, though side effects become more common at higher doses. The most frequent ones are stomach-related—nausea, diarrhea, constipation, vomiting, and heartburn—plus headache, insomnia, dizziness, and dry mouth.

A caution: SAMe can trigger mania in people with bipolar disorder, so it's not appropriate if you have that condition. The safety data for long-term use isn't well established, so use it only under the guidance of your own healthcare provider.

Side effects, ingredient by ingredient Same

Meds to double-check

Moderate interaction found
Known Interaction Concern · database check
Moderate identified

The most serious documented interaction for these ingredients is Moderate. Check your medications for a personalized result.

Why this rating?
  • 1 of the 1 matched ingredient can interact with medications — Same.
  • The most serious interaction on file is rated Moderate.
  • Some involve high-stakes drug classes: Parkinson's medications.
  • For scale: 189 individual medications appear in the full list. A big number alone doesn't make a product dangerous — what matters is whether YOUR medication is on it, so run yours through the interaction checker on this page.

Before taking this product, check with your own doctor or pharmacist if you take serotonergic drugs (antidepressants like SSRIs, SNRIs, or tricyclics; migraine drugs like triptans; or pain medications like tramadol)—SAMe may raise the risk of serotonin syndrome. Also check if you take levodopa for Parkinson disease, since SAMe may reduce how well it works.

Check your own medication Run your meds through the checker above

The bottom line

Scorecard at a glanceFully disclosed formula with clinical evidence supporting its stated purpose. Moderate medication interactions have been identified, and safety information is well characterized.

SAMe may help if you have osteoarthritis or depression, but it's not for everyone. Steer clear if you take serotonergic drugs or levodopa without checking first—the interactions can be serious.

If you have bipolar disorder, don't use it. Talk with your doctor or pharmacist before starting to make sure it fits your health picture.

Educational only — not medical advice; always confirm with your pharmacist. Our editorial policy · How we use AI

Assessment coverage: 1 of 1 active ingredient matched to our full ingredient reviews (monographs). Based on the product label dated Nov 21, 2016.

This Scorecard evaluates available label information, ingredient evidence, and known medication-safety considerations. It does not independently verify product identity, purity, potency, contamination, or manufacturing quality. How these ratings are computed

At a glance

General information

Key facts about Double Strength SAM-e 400 mg, straight from the product label.

Brand Puritan's Pride
Barcode (UPC) 025077131853
Net contents 30 Enteric Coated Caplet(s)
Market status On market
Date entered into DSLD Nov 21, 2016
DSLD ID 67000
Product type Non-nutrient/non-botanical
Supplement form Other (e.g. Tea Bag)
Dietary claims / uses All Other, Structure/Function
Intended target group(s) Vegetarian, Adult (18 - 50 Years), Gluten Free, Dairy Free, Sugar Free
From the label
Everything in this section is reproduced from the manufacturer’s own product label — it’s the label speaking, not HelloPharmacist. We show it so you can see exactly what the maker states; we don’t verify or endorse those statements.

Supplement Facts

The label details for Double Strength SAM-e 400 mg by Puritan's Pride, sourced from the NIH Dietary Supplement Label Database.

Supplement Facts

Daily Value (DV) Target Group(s):
Adults and children 4 or more years of age
Minimum serving Sizes:
1 Caplet(s)
Maximum serving Sizes:
1 Caplet(s)
UPC/BARCODE
025077131853
IngredientAmount% DV
S-Adenosylmethionine400 mg--

Other ingredients: Vegetable Cellulose, Polymethacrylate, Contains 2% of

Tap any ingredient to jump to its full detail below.

Label statements
These statements are the manufacturer’s wording, reproduced from the product label — the label is saying it, not HelloPharmacist. We don’t verify or endorse them.
Precautions

Keep out of reach of children.

Do not use if blister seal is cut, torn or open.

Warning: If you are pregnant, nursing, taking any medications or have any medical condition, consult your doctor before use.

Discontinue use and consult your doctor if any adverse reactions occur.

Storage

Store at room temperature.

Brand IP Statement(s)

2016 Puritan’s Pride, Inc.

General

Item # 13185 B36222 06C

General Statements

Part No. 22-13186

Supports mood & emotional well-being* Promotes healthy joint function & comfort*

SAM-e is a revolutionary supplement. Because of its popularity and use, it has received widespread exposure in the press. Information has appeared in newspapers, magazines, on the Internet, or simply through word of mouth. Whether you’re a first-time SAM-e user, or have been a fan for years, you probably have some questions. Please see the enclosed package insert for more information.

All living things contain SAM-e (S-adenosylmethionine). The body makes SAM-e from the amino acid methionine. However, you may not be able to obtain sufficient methionine levels simply by ingesting food. In addition, because of age or other factors, levels of SAM-e can fluctuate or decline. Supplementation with SAM-e is the easiest way to increase intake.

SAM-e is involved in over 35 biochemical reactions involving enzymatic transmethylation.* The methylation process is the mechanism by which the body rids itself of unwanted compounds, synthesizes neurotransmitters, nourishes cartilage, regulates enzyme activity within the cell and helps maintain the flexibility of cell membranes.* Science has been looking into this remarkable supplement and have found, SAM-e: ~ Supports mood and emotional well-being* ~ Promotes healthy joint function and comfort*

SAM-e (S-adenosylmethionine) was discovered in Italy in 1952. The subject of extensive studies, SAM-e has been used in Europe since 1975. It was one of Europe’s best kept secrets until recently, when it became available in the U.S. SAM-e helps promote a positive mood and emotional well-being.* A note about our enteric coating: The enteric coating helps the breakdown of SAM-e occur in the small intestine. In addition, the enteric coating is designed to protect SAM-e from moisture and serve as a protective barrier so that SAM-e can be absorbed where it can provide you with the greatest benefits.

FDA Statement of Identity

Vegetarian Dietary Supplement

Vegetarian Dietary Supplement

FDA Disclaimer Statement

*These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure or prevent any disease.

Suggested/Recommended/Usage/Directions

Directions: For adults, take one (1) caplet three times daily, preferably on an empty stomach. In order to obtain maximum benefits, SAM-e should be taken at least 30 minutes prior to a meal.

Formulation

No Artificial Flavor, No Preservatives, No Sugar, No Milk, No Lactose, No Soy, No Gluten, No Wheat, No Yeast, No Fish.

Is this label outdated? Report a formula or label change and our pharmacy team will review it.

See for yourself

Double Strength SAM-e 400 mg by Puritan's Pride label

The label scan from the NIH Dietary Supplement Label Database. Tap to enlarge.

Double Strength SAM-e 400 mg label

Label images are published by the NIH Dietary Supplement Label Database for the version of this product on file. Always read your actual product label.

View the full label (PDF)
What’s inside

The Ingredients in Double Strength SAM-e 400 mg by Puritan's Pride

This is the 1 active ingredient this product is made of. Select it to open its full monograph.

Serving size1 Caplet(s) Dosage formOther (e.g. Tea Bag) Amounts shown are per serving.

S-Adenosylmethionine

Interacts with
189 drugs
400 mg per serving

SAM-e is a compound your body makes naturally that is sold as a supplement, most often for depression and osteoarthritis. Some research suggests it ma...

S-Adenosylmethionine monograph & interactions

Other (inactive) ingredients: Vegetable Cellulose, Polymethacrylate, Contains 2% of. These complete the product’s ingredient list but are not active constituents.

Interaction report

Double Strength SAM-e 400 mg by Puritan's Pride Drug Interactions

Want to check YOUR meds against Double Strength SAM-e 400 mg?

Ask about interactions with your drugs in plain English — “Can I take it with lisinopril?” — and we find you the answer in seconds, ingredient by ingredient.

 Go to the checker
189Drugs
189 Moderate

Ingredients driving the most interactions

S-Adenosylmethionine 189

Individual Drug Interactions

The ingredients in Double Strength SAM-e 400 mg interact with 189 drugs. Click any drug to see the details.

1 of the 1 ingredient in Double Strength SAM-e 400 mg interact with drugs. Each result below shows which ingredient is responsible. S-Adenosylmethionine

Each ingredient & the kinds of drugs it affects

For each ingredient in Double Strength SAM-e 400 mg with known interactions, here are the types of medications it can affect. Open any type for the detail — or search your exact drug in the checker above.

S-Adenosylmethionine2 drug types · 189 drugs

Levodopa

SAMe might reduce the effectiveness of levodopa.
SAMe methylates levodopa, which might reduce its effectiveness for treating Parkinson disease.

Likelihood Possible Evidence D
Serotonergic Drugs

Taking SAMe with serotonergic drugs might increase the risk of serotonin syndrome and other serotonergic side effects.
SAMe has serotonergic effects. Theoretically, combining serotonergic drugs with SAMe might increase the risk of serotonergic side effects, including serotonin syndrome and cerebral vasoconstrictive disorders. In one case report, SAMe 100 mg intramuscularly was given daily with clomipramine (Anafranil) 25 mg per day. When the clomipramine dose was increased to 75 mg per day the patient experienced serotonin syndrome about 48-72 hours later, requiring hospitalization.

Likelihood Possible Evidence D
S-Adenosylmethionine full monograph & interactions
The maker

Brand information

Manufacturer and brand details for Double Strength SAM-e 400 mg, from the product label.

Puritan's Pride

See all Puritan's Pride products
Name
Puritan's Pride, Inc.
City
Ronkonkoma
State
NY
ZipCode
11779
Phone Number
1-800-645-1030
Web Address
www.puritan.com
Pharmacist Counseling Corner

Double Strength SAM-e 400 mg by Puritan's Pride: Common Questions

Does Double Strength SAM-e 400 mg by Puritan's Pride interact with any medications?
Yes. Based on its ingredients, Double Strength SAM-e 400 mg has a known interaction with 189 medications. Use the checker to see how it interacts with a specific drug.
How can one product interact with so many drugs?
Double Strength SAM-e 400 mg contains a single active ingredient, and that one ingredient can interact with many different medications on its own. We check it against each medication and show the mechanism responsible.
Where does this information come from?
The product label data comes from the NIH Dietary Supplement Label Database (DSLD); the interaction data is built on the Natural Medicines database and reviewed by HelloPharmacist pharmacists.
Can I take SAMe if I have bipolar disorder?
No. SAMe can trigger mania in people with bipolar disorder, so it's not safe for you. Talk with your doctor or pharmacist about other options.
What are the most common side effects?
The most frequent ones are stomach upset—nausea, diarrhea, constipation, vomiting, and heartburn—along with headache, insomnia, dizziness, and dry mouth. Side effects are more likely at higher doses. Most people tolerate it well at the typical dose.
Is SAMe safe during pregnancy?
The data rates it as possibly safe during pregnancy, but the evidence isn't strong. Because safety isn't well established, talk with your doctor or pharmacist for personalized advice before taking it if you're pregnant or planning to become pregnant.
Does SAMe actually work for depression?
The evidence rates SAMe as possibly effective for depression, meaning there's some support but it's not conclusive. Whether it's the right choice for you depends on your specific situation—your doctor or pharmacist can help you weigh it against other options.
Can I stop taking SAMe anytime, or do I need to taper off?
Our data doesn't cover how to stop taking SAMe. Talk with your doctor or pharmacist about the safest way to stop, especially if you've been taking it for a while.

Written and reviewed by the HelloPharmacist editorial staff. Our editorial policy

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Label information is sourced from the NIH Dietary Supplement Label Database and reflects the product version on file; always read your actual product label. This page is for education only and is not a substitute for professional medical advice. Confirm with your pharmacist or doctor before combining supplements and medications.

Double Strength SAM-e 400 mg label
Go deeper

The Full Monographs Behind Double Strength SAM-e 400 mg’s Ingredients

Every ingredient we hold a full HelloPharmacist monograph for — uses, evidence, safety, and the complete interaction list.

Herb & supplement monograph

Same

Interacts with 189 drugs

SAM-e is a compound your body makes naturally that is sold as a supplement, most often for depression and osteoarthritis. Some research suggests it may help with these conditions, but the qu...

Read the full Same monograph →
Sources

Sources & How We Checked

Double Strength SAM-e 400 mg's label data comes from the NIH Dietary Supplement Label Database; the ingredient interaction data is from the Natural Medicines database, reviewed by our pharmacists.

Content is written and reviewed by licensed HelloPharmacist pharmacists. See our data sources and editorial standards for how this information is built and checked.

The 31 references behind this product’s interaction data

Every citation that drives the interaction findings for this product’s ingredients, from the evidence-graded Natural Medicines (TRC Healthcare) database. Open an ingredient to browse its citations — links open the study on PubMed or the publisher’s site.

Same 31 references
  1. Perna AF, Castaldo P, Ingrosso D, et al. Homocysteine, a new cardiovascular risk factor, is also a powerful uremic toxin. J Nephrol 1999;12:230-40.
  2. Mato JM, Camara J, Fernandez de Paz J, et al. S-adenosylmethionine in alcoholic liver cirrhosis: a randomized, placebo-controlled, double-blind, multicenter clinical trial. J Hepatol 1999;30:1081-9. PubMed
  3. Iruela LM, Minguez L, Merino J, Monedero G. Toxic interaction of S-adenosylmethionine and clomipramine. Am J Psychiatry 1993;150:522. PubMed
  4. Bradley JD, Flusser D, Katz BP, et al. A randomized, double blind, placebo controlled trial of intravenous loading with S-adenosylmethionine (SAM) followed by oral SAM therapy in patients with knee osteoarthritis. J Rheumatol 1994;21:905-11.
  5. Berlanga C, Ortega-Soto HA, Ontiveros M, Senties H. Efficacy of S-adenosyl-L-methionine in speeding the onset of action of imipramine. Psychiatry Res 1992;44:257-62. PubMed
  6. Kagan BL, Sultzer DL, Rosenlicht N, Gerner RH. Oral S-adenosylmethionine in depression: a randomized, double-blind, placebo-controlled trial. Am J Psychiatry 1990;147:591-5. PubMed
  7. Rosenbaum JF, Fava M, Falk WE, et al. The antidepressant potential of oral S-adenosyl-l-methionine. Acta Psychiatr Scand 1990;81:432-6. PubMed
  8. Domljan Z, Vrhovac B, Durrigl T, Pucar I. A double-blind trial of ademetionine vs naproxen in activated gonarthrosis. Int J Clin Pharmacol Ther Toxicol 1989;27:329-33.
  9. Konig B. A long-term (two years) clinical trial with S-adenosylmethionine for the treatment of osteoarthritis. Am J Med 1987;83:89-94. PubMed
  10. Lipinski JF, Cohen BM, Frankenburg F, et al. Open trial of S-adenosylmethionine for treatment of depression. Am J Psychiatry 1984;141:448-50.
  11. Almasio P, Bortolini M, Pagliaro L, Coltorti M. Role of S-adenosyl-L-methionine in the treatment of intrahepatic cholestasis. Drugs 1990;40:111-23. PubMed
  12. Friedel HA, Goa KL, Benfield P. S-adenosyl-L-methionine. A review of its pharmacological properties and therapeutic potential in liver dysfunction and affective disorders in relation to its physiological role in cell metabolism. Drugs 1989;38:389-416. PubMed
  13. Bottiglieri T, Hyland K, Reynolds EH. The clinical potential of ademetionine (S-adenosylmethionine) in neurological disorders. Drugs 1994;48:137-52. PubMed
  14. Frezza M, Centini G, Cammareri G, et al. S-adenosylmethionine for the treatment of intrahepatic cholestasis of pregnancy. Results of a controlled clinical trial. Hepatogastroenterology 1990;37:122-5.
  15. Singhal AB, Caviness VS, Begleiter AF, et al. Cerebral vasoconstriction and stroke after use of serotonergic drugs. Neurology 2002;58:130-3. PubMed
  16. Charlton CG, Crowell B Jr. Parkinson's disease-like effects of S-adenosyl-L-methionine: effects of L-dopa. Pharmacol Biochem Behav 1992;43:423-31..
  17. Goren JL, Stoll AL, Damico KE, et al. Bioavailability and lack of toxicity of S-adenosyl-L-methionine (SAMe) in humans. Pharmacotherapy 2004;24:1501-7. PubMed
  18. Arnold O, Saletu B, Anderer P, et al. Double-blind, placebo-controlled pharmacodynamic studies with a nutraceutical and a pharmaceutical dose of ademetionine (SAMe) in elderly subjects, utilizing EEG mapping and psychometry. Eur Neuropsychopharmacol 2005; PubMed
  19. Nelson JC. S-adenosyl methionine (SAMe) augmentation in major depressive disorder. (Editorial). Am J Psychiatry 2010;167:889-91.
  20. Kim J, Lee EY, Koh EM, et al. Comparative clinical trial of S-adenosylmethionine versus nabumetone for the treatment of knee osteoarthritis: an 8-week, multicenter, randomized, double-blind, double-dummy, Phase IV study in Korean patients. Clin Ther 2009; PubMed
  21. Manzillo G, Piccinino F, Surrenti C, et al. Multicentre double-blind placebo-controlled study of intravenous and oral S-adenosyl-L-methionine (SAMe) in cholestatic patients with liver disease. Drug Invest 1992;4 (Suppl 4):90-100. DOI
  22. Carrieri PB, Indaco A, Gentile S, et al. S-adenosylmethionine treatment of depressioin in patients with Parkinson's disease: a double-blind, crossover study versus placebo. Curr Ther Res 1990;48(1):154-60.
  23. Pancheri P, Scapicchio P, Delle Chiaie R. A double-blind, randomized parallel-group, efficacy and safety study of intramuscular S-adenosyl-L-methionine 1,4-butanedisulphonate (SAMe) versus imipramine in patients with major depressive disorder. Int J Neuro PubMed
  24. Medici V., Virata M. C., Peerson J. M., Stabler S. P., French S. W., Gregory J. F. III, Albanese A., Bowlus C. L., Devaraj S., Panacek E. A., Richards J. R., Halsted C. H. S-adenosyl-L-methionine treatment for alcoholic liver disease: a double-blinded, ra
  25. Chitiva, H., Audivert, F., and Alvarez, C. Suicide attempt by self-burning associated with ingestion of S-adenosylmethionine: a review of the literature and case report. J.Nerv.Ment.Dis. 2012;200(1):99-101. PubMed
  26. Carney, M. W., Edeh, J., Bottiglieri, T., Reynolds, E. M., and Toone, B. K. Affective illness and S-adenosyl methionine: a preliminary report. Clin Neuropharmacol. 1986;9(4):379-385. PubMed
  27. Miccoli, L., Porro, V., and Bertolino, A. Comparison between the antidepressant activity and of S- adenosylmethionine (SAMe) and that of some tricyclic drugs. Acta Neurol (Napoli) 1978;33 (3):243-255.
  28. Bacci, Ballerini F., Lopez, Anguera A., Alcaraz, P., and Hernandez, Reyes N. [SAMe in the management of postconcussional syndrome]. Medicina Clinica (Barc.) 1983;80(4):161-164.
  29. Muscettola G, Galzenati M, Balbi A. SAMe versus placebo: a double blind comparison in major depressive disorders. Advances in Biochemical Psychopharmacology 1982;32:151-6.
  30. Capretto C, Cremona C, and Canaparo L. A double-blind controlled study of S-adenosylmethionine (SAMe) v. ibuprofen in gonarthrosis, coxarthrosis and spondylarthrosis. Clin Trials J 1985;22(1):15-24.
  31. Ancarani E, Biondi B, Bolletta A, et al. Major depression complicating hemodialysis in patients with chronic renal failure: a multicenter, double-blind, controlled clinical trial of S-adenosyl-L-methionine versus placebo. Curr Ther Res 1993;54(6):680-6. DOI

See these in context on the Same monograph →

Parts of this content are provided by the Therapeutic Research Center, LLC.

DISCLAIMER: Currently this does not check for drug-drug interactions. This is not an all-inclusive comprehensive list of potential interactions and is for informational purposes only. Not all interactions are known or well-reported in the scientific literature, and new interactions are continually being reported. Input is needed from a qualified healthcare provider including a pharmacist before starting any therapy. Application of clinical judgment is necessary.

© 2021 Therapeutic Research Center, LLC

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