Oral fenugreek seed consumption and serotonin syndrome

To the Editor

Serotonin syndrome is an uncommon but serious adverse effect of serotonergic agents, induced by overactivation of serotonin receptors (Volpi-Abadie et al., 2013). While often caused by combination of serotonergic agents, it can occur with monotherapy. Moreover, the list of drugs known to cause serotonin syndrome is growing. The clinical presentation varies widely, but can include altered mental state, autonomic hyperactivity and neuromuscular abnormalities. The mainstays of management are ceasing all serotonergic agents, and supportive care. Benzodiazepines can be used for symptom management, and in severe cases, serotonin antagonists may be required. Symptoms usually self-resolve within 24 hours.

We present a case of serotonin syndrome where there was potential interaction between sertraline and oral fenugreek supplements – an interaction that has not previously been reported.

A 38-year-old woman presented with post-natal depression and anxiety 6 months after the birth of her first child, with increasing thoughts of harming herself and baby. She reported no regular medication, with a history of fluoxetine prescription in her adolescence, without any adverse event. Following admission to an adult inpatient psychiatry ward, she was commenced on sertraline (due to ongoing breastfeeding), 25 mg the first day, with up-titration to 50 mg the following day. After the second dose, she developed serotonin syndrome, with nausea, anxiety, mydriasis, diaphoresis, tachycardia, hyperreflexia and clonus, requiring transfer to a medical unit for monitoring. Further history revealed daily fenugreek supplements to aid lactation. Sertraline and fenugreek were subsequently ceased, with supportive care and diazepam for symptom control. The serotonin syndrome self-resolved within 24 hours.

There is a plausible mechanism for fenugreek (Trigonella foenum-graecum L.) to contribute to serotonin syndrome. A study in mice showed that 4-hydroxyisoleucine (4-HI), which makes up about 80% of the free amino acids in fenugreek seeds, significantly increased the number of head twitches induced by 5-hydroxytryptophan (5-HTP), the precursor of serotonin (Gaur et al., 2012). The authors explained this was likely due to 4-HI increasing the turnover of serotonin in the brain. If 4-HI has a similar effect in humans, it could explain why fenugreek may induce serotonin syndrome when combined with another serotonergic agent.

The potential for fenugreek to contribute to serotonin syndrome warrants further study. It is estimated that between 15% and 43% of breastfeeding women use herbal galactogogues, as in the case described, potentially heightening the risk of serotonin syndrome (Mortel and Mehta, 2013). This case highlights not only a novel interaction but also the importance of a full medication history in breastfeeding women involving enquiry regarding herbal supplements.