From the Guidelines
The most suggestive symptom of serotonin syndrome is clonus, particularly ocular clonus (rhythmic eye movements) or inducible clonus in the extremities. Serotonin syndrome is characterized by a triad of mental status changes, autonomic hyperactivity, and neuromuscular abnormalities, but clonus is considered the most specific finding, as noted in the study published in Pediatrics in 2016 1. This hyperreflexia and muscle rigidity occurs because excessive serotonin stimulates the 5-HT2A receptors in the central nervous system, leading to these involuntary muscle contractions. Other important symptoms include:
- Hyperthermia
- Agitation
- Tremor
- Diaphoresis
- Hyperreflexia However, these can be present in other conditions as well. Serotonin syndrome typically develops rapidly after starting or increasing the dose of serotonergic medications such as SSRIs, SNRIs, MAOIs, triptans, or certain antibiotics like linezolid. The presence of clonus in a patient taking serotonergic medications should raise immediate concern for serotonin syndrome and prompt discontinuation of the offending agents and supportive care, as outlined in the treatment guidelines 1. It is essential to recognize serotonin syndrome early, as it can lead to severe morbidity and mortality, with a mortality rate of approximately 11% 1.
From the Research
Symptoms of Serotonin Syndrome
The symptoms of serotonin syndrome can be diverse and nonspecific, making it challenging to diagnose. According to 2, serotonin syndrome classically consists of a triad of signs and symptoms broadly characterized as:
- Alteration of mental status
- Abnormalities of neuromuscular tone
- Autonomic hyperactivity
Clinical Features
As mentioned in 3 and 4, the central clinical features of serotonin syndrome consist of:
- Neuromuscular excitation
- Autonomic dysfunction
- Altered mental status
These features occur in a patient undergoing new or altered serotonergic therapy.
Diagnostic Criteria
The diagnosis of serotonin syndrome requires a history of exposure to agents active at serotonin receptors and the presence of alterations in mental status, autonomic instability, and neuromuscular abnormalities, such as tremor, hyperreflexia, or myoclonus, as stated in 5.
Most Suggestive Symptom
While there are various symptoms associated with serotonin syndrome, altered mental status is a key feature that is often present. However, the most suggestive symptom is not explicitly stated in the provided studies. Nevertheless, according to 2, 3, and 4, a combination of neuromuscular abnormalities, autonomic hyperactivity, and mental state changes is characteristic of serotonin syndrome.
In particular, 5 highlights the importance of alterations in mental status, autonomic instability, and neuromuscular abnormalities, such as tremor, hyperreflexia, or myoclonus, in the diagnosis of serotonin syndrome. Therefore, it can be inferred that the presence of these symptoms, especially altered mental status and neuromuscular abnormalities, is highly suggestive of serotonin syndrome, as supported by 2, 3, 4, 5.