Tryptophan, 5-HTP and Serotonin Syndrome: Interactions With Antidepressants and Other Medicines
Tryptophan and 5-HTP raise serotonin, so they may add to antidepressants and other medicines. Learn the warning signs of serotonin syndrome, what sources say and when to ask a pharmacist.
Content last updated . This page has not been medically reviewed.
Urgent: signs of serotonin syndrome
Serotonin syndrome is a potentially life-threatening reaction in which the body has too much serotonin. [1] Symptoms occur within minutes to hours of taking medicines that can cause it, and include agitation or restlessness, abnormal eye movements, diarrhea, fast heartbeat and high blood pressure, and hallucinations. [1] Untreated, it can be deadly. [1] If you have these symptoms after starting or increasing a medicine or supplement, get medical help right away; in the US call 911. MedlinePlus says to contact your provider right away if you have symptoms. [1] If you are only worried about a combination you already take, do not stop a prescribed medicine on your own: MedlinePlus says to talk to your health care provider about concerns first. [1]The short answer
Tryptophan is an essential amino acid. [2] 5-HTP (5-hydroxytryptophan) is the immediate step between tryptophan and serotonin. [3] Both are sold as supplements. For 5-HTP, a cancer-center monograph tells people who take antidepressants or other drugs that affect serotonin to avoid it without a physician's supervision. [4] The warnings below are mostly precautions and case reports, not large trials.Evidence labels used here: established (for how serotonin syndrome occurs), insufficient evidence, mixed, evidence of harm (case reports only), Proper evidence not found.
How the sources define the terms
- Tryptophan is one of the nine essential amino acids and is part of protein. [2]
- 5-HTP is made from tryptophan and is not itself a protein-building amino acid; it is the immediate precursor of serotonin. [3] It crosses the blood-brain barrier and increases serotonin production. [4]
- Serotonin syndrome most often happens when two or more medicines or drugs that affect serotonin are taken together. [1] It is more likely when you first start a medicine or increase the dose. [1]
What the sources say about combinations
| Combination | What the source found | Strength |
|---|---|---|
| Common antidepressants (SSRIs, SNRIs) with triptan migraine medicines | MedlinePlus gives this as an example of a combination that can cause serotonin syndrome; MAOI antidepressants can also cause it with other medicines, including meperidine, fentanyl and dextromethorphan. [1] | Established for these medicines |
| 5-HTP with SSRIs, MAOIs or tricyclic antidepressants | A cancer-center monograph (updated June 2022) says people on these drugs should avoid 5-HTP without a physician's supervision because of the theoretical potential for serotonin syndrome. [4] | Precaution; theoretical |
| 5-HTP with linezolid (an antibiotic with MAOI action) | The same monograph cites a case report of serotonin syndrome. [4] | Evidence of harm (single case report) |
| 5-HTP with St John's wort or SAM-e | Advises avoiding other supplements that may also affect serotonin. [4] | Precaution |
| L-tryptophan with fluoxetine | A 1986 report titled "five case reports" describes a toxic reaction after combining the two. [5] The record has no abstract, so we could not read the details. | Evidence of harm (old case reports) |
Doctors diagnose serotonin syndrome partly by asking about prescription drugs, over-the-counter medicines and dietary supplement use, so tell every clinician what you take. [6] Treatment is hospital-based and usually includes stopping the medicines that caused it. [1]
Do tryptophan or 5-HTP work? (brief)
A Cochrane review found 108 trials but only two (64 patients) of enough quality; they were better than placebo but the evidence was not conclusive, and the authors said clinical usefulness was limited. [7] Details by use are on Amino Acids, Sleep, Anxiety and Depression. If you are struggling with low mood or thoughts of harm, contact a clinician; in the US you can call or text 988 (Suicide & Crisis Lifeline).Contamination history and product quality
The use of L-tryptophan as a dietary supplement was discontinued in 1989 after an outbreak of eosinophilia-myalgia syndrome (EMS) traced to a contaminated synthetic product from a single manufacturer. [3] EMS is a rare condition with inflammation of muscles, skin and lungs. [8] A 2023 review (some authors declare employment by a company) found no clear conclusion on which impurities caused it. [8] For 5-HTP, one review argued no definitive toxicity cases had emerged and a "peak X" was a minor artifact. [3] Other researchers identified the peak X compound as a putative neurotoxin in case-linked and over-the-counter samples. [9] The evidence is mixed. Product quality varies; see Quality testing and certifications.Other cautions
- 5-HTP can make a urine test for carcinoid tumors (5-HIAA) inaccurate. [4]
- A case report describes pain, swelling and rash in a patient given carbidopa with 5-HTP. [4]
- Pregnancy, breastfeeding, children, kidney or liver disease: not described in the sources we read for these supplements. Ask a clinician; see Pregnancy and breastfeeding.
- Before surgery tell the team about all supplements: Supplements before surgery.
- The sources we read discuss supplements and medicines; they do not describe tryptophan in ordinary food as a cause.
- More: Tryptophan profile, 5-HTP profile, the medicine interaction table and How interactions work. Talk to a clinician or pharmacist before combining.
Frequently asked questions
Can I take 5-HTP or tryptophan with an antidepressant?
Do not decide alone. A monograph advises people on SSRIs, MAOIs or tricyclics to avoid 5-HTP without physician supervision. [4] Ask a clinician or pharmacist, and do not stop your antidepressant on your own. [1]
What does serotonin syndrome feel like?
Agitation, abnormal eye movements, diarrhea, fast heartbeat, high blood pressure and hallucinations are listed. [1] Seek urgent care.
Is tryptophan in turkey or milk a risk with antidepressants?
The sources we read discuss supplements and medicines, not ordinary food, so we cannot say. Ask your pharmacist.
Why did L-tryptophan supplements stop in 1989?
An outbreak of EMS was traced to a contaminated synthetic product from one manufacturer. [3]
Do these supplements treat depression?
A Cochrane review found the evidence insufficient to be conclusive. [7]
References
- MedlinePlus Medical Encyclopedia. Serotonin syndrome. US National Library of Medicine. Read 2026-10-22.
- MedlinePlus Medical Encyclopedia. Amino acids. US National Library of Medicine. Read 2026-10-22.
- Safety of 5-hydroxy-L-tryptophan. Toxicol Lett. 2004;150(1). PubMed 15068828.
- Memorial Sloan Kettering Cancer Center. 5-HTP (About Herbs, Botanicals and Other Products). Last updated 2 June 2022. Read 2026-10-22.
- Steiner W, Fontaine R. Toxic reaction following the combined administration of fluoxetine and L-tryptophan: five case reports. Biol Psychiatry. 1986;21(11):1067-71. PubMed 3488767 (record has no abstract).
- Serotonin syndrome. Ochsner J. 2013;13(4) (PMC3865832). Read 2026-10-22.
- Tryptophan and 5-hydroxytryptophan for depression. Cochrane Database Syst Rev. 2002;(1). PubMed 11869656.
- Safety concerns regarding impurities in L-Tryptophan associated with eosinophilia myalgia syndrome. Food Chem Toxicol. 2023. PubMed 37453474.
- Klarskov K, et al. Structural characterization of a case-implicated contaminant, "Peak X," in commercial preparations of 5-hydroxytryptophan. J Rheumatol. 2003;30(1):89-95. PubMed 12508395.
Education, not medical advice. This page is for general information. It does not diagnose or treat any condition and is not a substitute for care from a qualified health professional. Natural does not automatically mean safe. Ask a clinician or pharmacist before changing your care, especially if you take medication, are pregnant or breastfeeding, or have a health condition.