Herb & supplement monograph

Same Drug Interactions, Uses, Effectiveness, Safety & More

Medically reviewed by Dr. Brian Staiger, PharmD, BCPS ·Updated July 2026

What is this page for?

First and foremost: how Same interacts with medications. The heart of this page is the interaction list — every drug Same is known to interact with, and how serious each one is.

But these pages have grown well beyond that into a full monograph — what Same is, what people use it for and how strong the evidence is, its safety and side effects, and answers to the questions we’re asked most — written and reviewed by the clinical staff at HelloPharmacist. It’s educational information from our licensed clinical databases, not medical advice, and we don’t sell or endorse products. Our editorial policy

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Reviewed by licensed pharmacists Sourced from Natural Medicines

On this page

Same Drug Interactions: The Bottom Line

From the HelloPharmacist Editorial Team · Updated July 2026

Based on the available evidence, the overall risk of a clinically significant Same drug interaction appears low for most people, though anyone taking mood or Parkinson's medications should pay closer attention. None of the listed interactions are rated major, and nearly all rest on theoretical reasoning or limited case reports rather than well-controlled human studies.

Interactions deserving the most attention

The combination that deserves the most care is Same with serotonergic drugs, a group that includes many antidepressants, because Same itself acts on serotonin and adding it to these medicines could raise the risk of serotonin syndrome, a reaction marked by agitation, rapid heart rate, and high body temperature. This concern comes mainly from one case report, so it is not well established, but the potential outcome makes caution sensible. People taking levodopa for Parkinson's disease should also know that Same might chemically alter levodopa in a way that could make it work less well.

What the rest of the list means

The long list of interacting medications looks daunting, but most entries are there because they belong to the broad serotonergic group. These interactions are largely predicted from how Same works in the body, not from documented harm in people, so the sheer number overstates the real-world risk for most combinations.

Check your medications against Same

Based on HelloPharmacist’s Same interaction data and reviewed under our editorial standards.

Interaction report

Drugs that interact with Same

189 medications have a known interaction with Same, graded by severity. Select any drug for the full evidence-based detail.

Don’t want to scroll the list? Just ask.

Tell us the medications you take and we’ll check each one against Same using our pharmacist-reviewed interaction data.

AI summaries are generated from our Same interaction data for education only — always confirm with your pharmacist. How we use AI

2,830 drugs

Read The List Like a Pharmacist

What Severity, Likelihood & Evidence Mean

Severity — How Serious It Can Be

Major. Clinically significant; generally best avoided, or used only under direct professional supervision.
Moderate. May need monitoring, a dose adjustment, or separating the times you take each one.
Minor. Generally not clinically significant, but still worth noting and mentioning to your pharmacist.
No known interaction. Checked against our sources with nothing documented — not the same as proven safety.

Likelihood — How Well It’s Documented

Likely. Well-controlled human studies have demonstrated the likely existence of this interaction
Probable. Interaction has not been documented in well-controlled studies, however, the interaction has been demonstrated in some small human studies or in controlled animal studies in conjunction with multiple case reports.
Possible. Interaction has been documented in animal or in lab research, or the interaction has been documented in humans but is limited to case reports or conflicting clinical research exists
Unlikely. Interaction has been demonstrated in animal or in lab research but has been shown not to occur in humans.

Where This Data Comes From

Interaction records are evidence-graded and sourced from the Natural Medicines database (TRC Healthcare), the same reference used by pharmacists and hospitals.
Each drug listed above links to the full report for that exact Same combination — clinical detail, likelihood, evidence level, and citations.
Content is reviewed by licensed HelloPharmacist pharmacists — see our data sources and editorial standards.

The big picture

The kinds of drugs Same affects

Every type of medication (drug category) Same is known to interact with. Open any category for the detail — or search your exact drug in the checker above.

All 2 drug categories Same interacts with

LevodopaSerotonergic 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

Monograph

Same: Uses, Safety & Side Effects

Medically reviewed by Dr. Brian Staiger, PharmD, BCPS · Reviewed July 2026 ·

The bottom line

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 quality of evidence is mixed and more study is needed. Talk with your pharmacist or doctor before trying it, especially if you take other medicines or have bipolar disorder.

Part used: Not a plant; a compound made naturally in the body (supplements are made synthetically)
Common forms: Enteric-coated tablets, capsules; less commonly injectable (used in some countries under medical supervision)

People commonly use it for

Depression
Osteoarthritis joint pain
Liver conditions
Fibromyalgia

Popular and traditional uses — not proof it works. See “Uses & effectiveness” below for the evidence.

Safety at a glance

OverallUse caution

Often well tolerated short-term, but it can cause stomach upset and may trigger mania in people with bipolar disorder.

PregnancyPossibly Safe

When used intravenously short-term during the third trimester of pregnancy. In two small-scale trials, SAMe 800 mg daily was used intravenously for 14...

Read the full pregnancy detail

BreastfeedingInsufficient reliable information

Insufficient reliable information available; avoid using.

Read the full breastfeeding detail

Pregnancy & breastfeeding ratings are from Natural Medicines (Therapeutic Research Center). Safety guidance is general; always confirm with your pharmacist or doctor for your situation.

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Overview

SAM-e (S-adenosyl-L-methionine) is a compound that your body makes naturally from an amino acid called methionine and a molecule called ATP. It is found in nearly every cell and plays a role in many chemical reactions, including making neurotransmitters (brain messengers) and processing hormones.

Because it is a natural body compound rather than a plant, the SAM-e in supplements is made in a laboratory. It is sold as a dietary supplement in the United States, and in some other countries it is available as a prescription medicine (called ademetionine).

People most often take SAM-e supplements to help with symptoms of depression and the joint pain of osteoarthritis. It has also been studied for liver problems and fibromyalgia.

How it works

SAM-e acts as a methyl donor, meaning it passes along small chemical groups (methyl groups) needed for many reactions in the body. This process, called methylation, helps make and break down neurotransmitters such as serotonin, dopamine, and norepinephrine, which may explain its possible role in mood.

SAM-e is also involved in building cartilage components, which is one proposed reason it might help with osteoarthritis. In the liver, it helps with detoxification reactions and the handling of bile.

Many of these mechanisms are based on laboratory and animal research, and it is not fully understood exactly how SAM-e taken by mouth produces its effects in people.

Effectiveness

Does Same work?

Here’s what the research actually shows for each use — graded by Natural Medicines and reviewed by Dr. Brian Staiger, PharmD.

Evidence overview · 22 uses evaluated

1 Likely effective 2 Possibly effective 19 Insufficient evidence

How to read these evidence grades

Natural Medicines’ 7-point scale. We show each rating’s label word-for-word.

1EffectiveStrong, consistent evidence it works.

2Likely EffectiveGood evidence, though not yet conclusive.

3Possibly EffectiveSome evidence suggests a benefit.

4Possibly IneffectiveSome evidence it may not help.

5Likely IneffectiveFairly strong evidence it doesn’t help.

6IneffectiveStrong evidence it doesn’t work.

7Insufficient Reliable Evidence to RateToo little research to say either way.

Likely Effective Osteoarthritis