From the Guidelines
Serotonin syndrome is a life-threatening condition characterized by a triad of mental status changes, autonomic hyperactivity, and neuromuscular abnormalities, which can rapidly progress to severe complications if not promptly recognized and treated. The symptoms of serotonin syndrome typically include mental status changes such as anxiety, agitation, confusion, and delirium, as well as autonomic symptoms like high fever, rapid heart rate, fluctuating blood pressure, sweating, dilated pupils, and flushing 1. Neuromuscular symptoms are particularly characteristic and include muscle rigidity, tremor, clonus, hyperreflexia, and myoclonus, which can be severe enough to lead to rhabdomyolysis, metabolic acidosis, and renal failure 1.
Some key symptoms to look out for include:
- Mental status changes: anxiety, agitation, confusion, delirium, and coma
- Autonomic symptoms: high fever, rapid heart rate, fluctuating blood pressure, sweating, dilated pupils, and flushing
- Neuromuscular symptoms: muscle rigidity, tremor, clonus, hyperreflexia, and myoclonus
- Gastrointestinal symptoms: nausea, vomiting, and diarrhea
It is essential to note that serotonin syndrome can be triggered by various medications, including SSRIs, SNRIs, MAOIs, triptans, certain opioids like tramadol, and some over-the-counter medications containing dextromethorphan 1. The condition typically develops rapidly, often within hours of taking a new serotonergic medication or increasing the dose of an existing one. Immediate medical attention is necessary if these symptoms appear after starting or changing serotonergic medications, as severe cases can progress to seizures, respiratory failure, and death if not treated promptly. Treatment often involves discontinuing the precipitating agent and providing supportive care, which may include benzodiazepines for agitation, management of hyperthermia, and autonomic instability, as well as consideration of serotonin2A antagonists like cyproheptadine in severe cases 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, the condition classically consists of a triad of signs and symptoms broadly characterized as:
- Alteration of mental status
- Abnormalities of neuromuscular tone
- Autonomic hyperactivity However, not all three triads of serotonin syndrome may occur simultaneously.
Clinical Manifestations
The clinical manifestations of serotonin syndrome can range from mild to life-threatening. As reported in 3, common symptoms include:
- Agitation
- Confusion
- Rapid heart rate
- High blood pressure
- Dilated pupils
- Muscle rigidity
- Tremors
- Sweating
- Diarrhea These symptoms can occur when serotonergic medications are taken alone or in combination, especially when a new medication is added or the dose of an existing medication is changed.
Specific Symptoms
Other studies have identified additional symptoms associated with serotonin syndrome. For example, 4 reports that patients may experience:
- Alterations in mental status
- Autonomic instability
- Neuromuscular abnormalities such as tremor, hyperreflexia, or myoclonus Similarly, 5 notes that the syndrome can be characterized by a constellation of symptoms including:
- Confusion
- Fever
- Shivering
- Diaphoresis
- Ataxia
- Hyperreflexia
- Myoclonus
- Diarrhea
Severity of Symptoms
The severity of serotonin syndrome can vary widely. As stated in 6, severe serotonin syndrome is usually precipitated by the simultaneous initiation of two or more serotonergic drugs, but the syndrome can also occur after the initiation of a single serotonergic drug in a susceptible individual. In some cases, the condition can be life-threatening, especially when caused by the combination of a monoamine oxidase inhibitor (MAOI) with serotonergic drugs.