From the Guidelines
Serotonin syndrome is a medical emergency that requires immediate discontinuation of the precipitating agent and supportive care, with a mortality rate of approximately 11% and significant morbidity, as reported in the 2016 study published in Pediatrics 1. The condition is characterized by a triad of symptoms: mental status changes, autonomic instability, and neuromuscular abnormalities.
- Mental status changes include agitation, confusion, and delirium
- Autonomic instability presents with high fever, sweating, rapid heart rate, and high blood pressure
- Neuromuscular abnormalities include tremor, rigidity, hyperreflexia, and muscle tone increase Treatment often involves discontinuing the precipitating agent and providing supportive care, which may include:
- Benzodiazepines for agitation
- Amelioration of hyperthermia
- Management of autonomic instability with IV fluids and other agents to address abnormal vital signs
- In severe cases, emergency sedation, neuromuscular paralysis, and intubation may be considered, as noted in the study 1 The use of cyproheptadine, a serotonin2A antagonist, may be considered in adult patients with severe serotonin syndrome, with a typical dosage of 12 to 24 mg over 24 hours, as described in the study 1. It is essential to inform all healthcare providers about all medications being taken to prevent dangerous combinations that could lead to serotonin syndrome. Key considerations in the diagnosis and treatment of serotonin syndrome include:
- Clinical diagnostic criteria, such as the Hunter criteria
- Laboratory and radiographic findings, although there are no pathognomonic tests
- Differentiation from other drug toxicity syndromes, such as neuroleptic malignant syndrome, malignant hyperthermia, and anticholinergic poisoning, as outlined in the study 1
From the Research
Definition and Causes of Serotonin Syndrome
- Serotonin syndrome (SS) is a rare and potentially life-threatening toxic state caused by an adverse drug reaction that leads to excessive central and peripheral serotonergic activity 2.
- It can occur after the use of serotonergic agents alone or in combination with monoamine oxidase inhibitors 2, 3.
- The combination of a monoamine oxidase inhibitor (MAOI) with serotonergic drugs is especially dangerous and may lead to the most severe form of the syndrome, and occasionally death 3.
Clinical Features and Diagnosis
- SS classically consists of a triad of signs and symptoms broadly characterized as alteration of mental status, abnormalities of neuromuscular tone, and autonomic hyperactivity 2.
- Clinical manifestations are diverse and nonspecific, which may lead to misdiagnosis 2, 4.
- The diagnosis of SS is based on the presence of clinical symptoms, which can include agitation, confusion, rapid heart rate, high blood pressure, dilated pupils, muscle rigidity, tremors, sweating, and diarrhea 4.
Management and Treatment
- Management of SS involves withdrawal of the offending agent(s), aggressive supportive care to treat hyperthermia and autonomic dysfunction, and occasionally the administration of serotonin antagonists--cyproheptadine or chlorpromazine 2, 5.
- In severe cases, benzodiazepines may be used to control agitation and muscle rigidity, while serotonin antagonists, such as cyproheptadine, may be used to reduce serotonin levels 4, 5.
- Rapid reversal of mydriasis in serotonin syndrome by cyproheptadine may serve as a specific suppressive test for the condition, and possibly may add to our understanding of the syndrome 5.
Prevention and Awareness
- Psychiatrists, clinicians, and general practitioners must develop increased awareness of SS due to the current increase in the use of serotonergic agents in clinical practice 2, 4.
- Family physicians play a key role in identifying and preventing serotonin syndrome by teaching patients to recognize symptoms and monitoring patients throughout therapy 6.
- There is a need for regular information updates and reminders to all those who prescribe medications to patients to prevent SS 4.