Serotonergic Medicines and Substance-Specific Evidence

Urgent help first

Serotonin syndrome is a potentially life-threatening reaction that most often occurs when two or more medicines or drugs that affect serotonin are taken together. [1] Symptoms occur within minutes to hours and can include agitation, abnormal eye movements, diarrhea, fast heartbeat, high blood pressure, hallucinations, increased body temperature, loss of coordination and overactive reflexes. [1] In the US call 911 for an emergency; US Poison Help is 1-800-222-1222. MedlinePlus advises not to stop a medicine without first talking to a provider. [1] This page is education only and never tells anyone to start, stop or change a medicine.

Why one chart does not work

"Serotonergic" covers very different drugs. [3] Antidepressants are another class again. A 2022 review concluded that risks differ: serotonergic drugs without MAOIs are low risk with psychedelics without MAOIs, while some combinations carry significant risk of serotonin toxicity and others are likely benign. [4] NIDA adds that reported cases of psychedelic drug interactions are exceedingly rare and that some researchers suspect interactions with serotonin-raising prescription medicines. [2]

That is why this page goes substance by substance. Evidence labels used: promising but limited, mixed, insufficient evidence, evidence of harm. See how we label evidence.

Substance by substance

The psilocybin result is the most important for readers who assume a combination is dangerous: in this one small study, the SSRI did not increase risks, but the authors said longer antidepressant pretreatment and studies in patients with psychiatric disorders are needed. [5] The study cannot say what happens with other antidepressants, other doses, long-term use or people with depression.

What systematic reviews say about the whole evidence base

A 2022 systematic review included 40 publications: 26 randomized studies in healthy adults, 3 epidemiologic studies and 11 case reports. [6] Participants in the trials were young healthy adults given a psychiatric medicine once or, rarely, for up to 14 days, so the findings are limited when extrapolating to real-world settings where medicines are taken daily for months or years. [6]

For ayahuasca, which contains an MAO inhibitor, see MAO-inhibiting preparations and interactions.

Other medicines and groups

• MAOI antidepressants: the label for one MAOI says it should not be used together with serotonin-acting agents because serious, sometimes fatal reactions have been reported. [9]
• Cough and cold ingredients and pain medicines: MedlinePlus says MAOIs can cause serotonin syndrome with medicines including meperidine, fentanyl and dextromethorphan. [1]

What the evidence cannot say

• Whether results in healthy volunteers apply to people with depression, anxiety or PTSD.
• What happens after months of antidepressant treatment, since the longest exposure in the controlled studies was short.
• Whether any particular product sold outside medicine contains what its label claims. See contamination and adulteration.

For related pages see psychedelic drug interactions and toxicology, interactions by drug class and talking with a health professional.