Serotonin Syndrome and Other Dangerous Medicine-Supplement Reaction Signs

Get help now if these signs appear after starting, raising or combining medicines or supplements. MedlinePlus (US) describes serotonin syndrome as "a potentially life-threatening reaction to certain medicines," and says to contact a provider right away if you have symptoms. [1] Call 911 if the person collapses, has a seizure, has trouble breathing or cannot be woken. [2] If you are unsure, Poison Help (1-800-222-1222, US) is free, confidential and open 24 hours a day, 7 days a week. [3] Do not stop a prescribed medicine on your own; MedlinePlus says to talk to your health care provider about concerns first. [1]

What serotonin syndrome is

Serotonin is a chemical made by some nerve cells. MedlinePlus says serotonin syndrome most often happens when two or more medicines or drugs that affect serotonin are taken together. [1] A 2023 review adds that it can also follow overdose of a single serotonin-active drug, and that the main features are muscle overactivity, changes in automatic body functions (autonomic dysfunction) and altered mental state, in someone with new or changed treatment. [4]

MedlinePlus says it is more likely when a person first starts a medicine or increases the dose. [1] Symptoms occur within minutes to hours. [1]

Warning signs

These signs are not specific to serotonin syndrome, and a clinician must check for other causes. Untreated, MedlinePlus says serotonin syndrome can be deadly, and people usually stay in hospital for at least 24 hours for close observation. [1] A review stresses that early recognition and treatment are crucial. [4]

Where herbs and supplements come in

St. John's wort (Hypericum perforatum, flowering tops). NCCIH (US, 2025) says taking St. John's wort with certain antidepressants or other drugs that affect serotonin "may lead to increased serotonin-related side effects, which can be serious." [5] Label: documented by NCCIH. See St. John's wort interactions and the St. John's wort profile.

5-HTP (5-hydroxytryptophan). A 2020 review describes 5-HTP as both a drug and a natural component of some dietary supplements, and states that excess 5-HTP can cause serotonin syndrome. [6] Label: reported in a review; we did not read the individual human case reports behind it, and we did not find a regulator statement on 5-HTP combined with specific medicines. Proper evidence not found, in the pages we searched (NCCIH, MedlinePlus, PubMed), for which amounts or combinations carry the risk. For the amino acid it comes from, see Tryptophan.

Street drugs. MedlinePlus lists methamphetamine and other amphetamines, cocaine, opiates, ecstasy and LSD as drugs that have been associated with serotonin syndrome. [1] Tell emergency staff everything that was taken; they are there to treat, not to judge.

Medicine groups named by MedlinePlus include SSRI and SNRI antidepressants, older antidepressants called MAOIs, and migraine medicines called triptans. [1] Ask a pharmacist about your own list; this page is not an interaction checker.

Other dangerous reactions to watch for

• Medicines that stop working as expected. NCCIH says St. John's wort can weaken the effects of many medicines, including some antidepressants, birth control pills, cyclosporine (used to prevent rejection of transplanted organs), some HIV drugs, some cancer medicines and warfarin. [5] Ask the prescriber or pharmacist before adding it, and tell them if you already use it.
• Liver injury. See Liver injury warning signs.
• Severe allergic reaction. See Severe allergic reactions to natural products.
• Anything else after a new product. NCCIH says supplements may interact with medicines or pose risks with certain medical problems. [7]

What to do

1. Treat sudden agitation, fever, sweating, shaking or confusion after a medicine change as urgent.
2. Bring the medicine and supplement containers and the list of everything taken.
3. Tell every provider about every supplement, including those bought without a prescription. [1]
4. Ask about reporting a problem. NCCIH points to the US Safety Reporting Portal. [7]

Related: How interactions work and Interactions by drug class.