Hidden Risks of Supplements and Serotonin Syndrome

Like drugs, many supplements have serotonergic effects, increasing the risk for serotonin syndrome when combined with other serotonergic agents. Most cases are mild, including symptoms of agitation, sweating, and tremor. But severe cases can lead to hyperthermia, muscle rigidity, and even death. Keep these on your radar.

A recent case report is putting the spotlight on black cohosh. A patient on stable treatment with sertraline 50 mg and duloxetine 60 mg daily developed serotonin syndrome after taking black cohosh extract 40 mg daily for 3 days. Black cohosh acts as an agonist at several serotonin receptor subtypes. Advise patients taking serotonergic drugs to be cautious.

Also watch out for SAMe – which is getting a lot of attention for its use in depression. SAMe seems to increase serotonin turnover as well as dopamine and norepinephrine levels. It’s been linked with serotonin syndrome when used with clomipramine. Tell patients that taking SAMe with other serotonergic supplements or drugs might increase the risk of serotonin syndrome and other serotonergic side effects.

Lastly, be aware that psilocybin has serotonin 2A (5-HT2A) receptor agonist activity – drugs that stimulate serotonin 2A receptors are most strongly linked to serotonin syndrome. While there isn’t any evidence of this interaction in humans to date, providers should be aware of its potential as interest in psilocybin increases.

Use our monograph filters to identify supplements by class, such as serotonergic agents. Also take advantage of our interactions checker to screen for possible interactions between multiple agents at once.