Drug & supplement interaction

Same + Dextromethorphan

Dextromethorphan brand names: Hold, Benylin Adult, Benylin Pediatric, Theraflu Thin Strips Long Acting Cough, Neo Citran Thin Strips Cough.

Moderate Interaction
The bottom line Moderate

Same has a moderate interaction with Dextromethorphan. Taking SAMe with serotonergic drugs might increase the risk of serotonin syndrome and other serotonergic side effects.

Read the full interaction report
SeverityModerate
LikelihoodPossible
EvidenceD
What do Severity, Likelihood & Evidence mean?
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Interaction report

Same and Dextromethorphan

Here is the interaction we found between these two, with the evidence behind it.

Moderate

SEROTONERGIC DRUGS

Why this applies to Dextromethorphan

Dextromethorphan falls under SEROTONERGIC DRUGS — the group Same interacts with.

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.
Severity Moderate Likelihood Possible Evidence D

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.

Dr. Brian Staiger, PharmD, BCPS
Dr. Brian Staiger explains PharmD, Clinical Pharmacist

Here's the thing to know about pairing SAM-e with dextromethorphan: both can nudge serotonin levels in your brain a little higher. Dextromethorphan, found in many cough syrups and cold strips, has mild serotonin-boosting activity of its own. SAM-e adds to that, so combining them could, in theory, raise your odds of a reaction called serotonin syndrome.

What might that look like? Things like agitation, a racing heart, sweating, shivering, muscle twitching, or feeling confused. To be fair, the evidence here is pretty thin (mostly a single case report with a different drug), so this isn't a common or expected problem. Still, if you take both regularly, it's worth a quick chat with your pharmacist or doctor before mixing them, especially if you also take antidepressants.

References
  1. Iruela LM, Minguez L, Merino J, Monedero G. Toxic interaction of S-adenosylmethionine and clomipramine. Am J Psychiatry 1993;150:522. PubMed
  2. 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
  3. 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
  4. Bottiglieri T, Hyland K, Reynolds EH. The clinical potential of ademetionine (S-adenosylmethionine) in neurological disorders. Drugs 1994;48:137-52. PubMed
  5. Singhal AB, Caviness VS, Begleiter AF, et al. Cerebral vasoconstriction and stroke after use of serotonergic drugs. Neurology 2002;58:130-3. PubMed

What These Ratings Mean

Every interaction above is graded three ways — here’s the key to each label.

Severity how clinically significant the interaction is
Major

Clinically significant. Avoid the combination, or use only under close professional supervision.

Moderate

Usually worth avoiding or managing — may need monitoring, a dose change, or timing apart.

Minor

Generally not serious. Be aware of it and mention it to your pharmacist.

Likelihood how strong the evidence is that the interaction actually happens in people
  • LikelyWell-controlled human studies have demonstrated the likely existence of this interaction.
  • ProbableInteraction 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.
  • PossibleInteraction 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.
  • UnlikelyInteraction has been demonstrated in animal or in lab research but has been shown not to occur in humans.
Evidence the quality of the studies behind the rating (graded A–D)
  • AHigh-quality meta-analysis (quantitative systematic review).
  • BCase-control study.
  • CConsensus.
  • DAnecdotal evidence.

These ratings are for information only. Never start, stop, or otherwise change your therapy before speaking with your provider.

Keep it in perspective

Same Also Interacts With Other Medications

Same has 188 moderate known drug interactions in our database — the Dextromethorphan one above is one of them. If you take anything else, check it against the full list below.

Taking anything else?

Check Another of Your Medications Against Same

Covers the 2,830 medications we’ve checked against Same. Pick one to open its full report.

From our Q&A

Questions About Same or Dextromethorphan

These are real questions from readers, answered by the pharmacists at HelloPharmacist — written by a person, not generated from a database. Each one covers Same or Dextromethorphan, not necessarily both, but if one is close to what you were about to ask it will usually go further than a database entry can:

Not quite your question? Ask our pharmacists directly — it is free, there is no account required, and answers usually come back within 24 hours.

Everything else you take

See Every Supplement That Interacts With Dextromethorphan

This page covers Same only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Dextromethorphan page lists 171 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: Activated Charcoal (major), Grapefruit (major), Lithium (major), St. John's Wort (major) and 1,3-dmaa (moderate).

By severity: 4 major · 125 moderate · 42 minor.

From our pharmacist’s overview on the Dextromethorphan page

“A glass of grapefruit juice can push dextromethorphan (Benylin, Hold, and other cough medicines) to higher levels than intended, one of four major-rated entries among the 171 supplements and herbs on file, and the list as a whole warrants real care. Most interactions trace back to the liver enzymes (CYP3A4 and CYP2D6) that clear dextro…”

Reviewed by 2 · Jul 18, 2026

Open the Dextromethorphan interaction page

One more smart check

Taking Same as Part of a Dietary Supplement Product? Check It for Interactions

We hold 9 real supplement products containing Same, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Same. Your product may carry other ingredients that interact with Dextromethorphan too, on top of Same — and those would not show on this page. Find your product and we’ll check every ingredient on its label:

How much people look this up

Where Same and Dextromethorphan Sit Against Everything Else

Out of every supplement and medication people look up on HelloPharmacist, here is where these two land this week — and which way each has been moving.

Supplement Same
Top half

#421 of 1,452 supplements looked up here in the last 7 days

29 days ago today
Medication Dextromethorphan
Top 25%

#330 of 2,830 medications looked up here in the last 7 days

29 days ago today

Position among everything looked up on this site, not a measure of how commonly either one is used or how important it is. A supplement can climb this list because of a news story. It counts every request to the page, automated ones included, and nothing here identifies anyone.

Supplement

About Same

What is Same?

Same
  • Depression
  • Osteoarthritis joint pain
  • Liver conditions
  • Fibromyalgia

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.

Read the full Same monograph & all interactions
Medication

About Dextromethorphan

What Is Dextromethorphan Used For?

Brand names: Hold, Benylin Adult, Benylin Pediatric, Theraflu Thin Strips Long Acting Cough, Neo Citran Thin Strips Cough

Dextromethorphan temporarily relieves cough due to minor throat and bronchial irritation. This can happen with the common cold or from inhaled irritants.

Some products are also labeled to help you get to sleep by reducing the urge to cough. Some labels also list helping reduce how intense the coughing is. Honey Works syrup, Premier Value Tussin Cough and CVS Long Acting Cough liquids are also labeled to help loosen phlegm (mucus) and thin bronchial secretions so they drain from the bronchial tubes.

See full Dextromethorphan drug information
Keep checking

Other Drugs & Same

Browse every other medication we’ve checked against Same — both the ones with a known interaction and the ones without. Select any drug for the full detail.

0Major
188Moderate
0Minor
2,641No known interaction
Moderate

188 interactions

Showing 60 of 188 moderate interactions — see all 188 on the Same page.

No interaction 2,641 drugs checked — show the list
Sources

Sources & How We Checked

Interaction details are evidence-graded and sourced from the Natural Medicines database. The medication overview comes from MedlinePlus.

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

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

Keep exploring
Pharmacist Counseling Corner

Taking Same and Dextromethorphan Together: Common Questions

Can you take Same with Dextromethorphan?
There is a moderate interaction, so it may be acceptable with monitoring or timing changes — but check with your pharmacist first. Read the full details on this page and confirm with your pharmacist before combining them.
How serious is the Same and Dextromethorphan interaction?
We rate it Moderate. This combination may require monitoring, a dose adjustment, or separating the times you take each one. Consult your pharmacist before using them together.

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

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This information is for education only and is not a substitute for professional medical advice. Always check with your pharmacist or doctor before starting, stopping, or combining supplements and medications.