From the Guidelines
No, diphenhydramine should not be used to treat serotonin syndrome. Serotonin syndrome is a potentially life-threatening condition caused by excessive serotonergic activity in the central nervous system, and it requires specific treatments that directly address the underlying mechanism. The first-line treatment for serotonin syndrome is discontinuation of all serotonergic medications and supportive care, as outlined in the study published in Pediatrics in 2016 1. For moderate to severe cases, cyproheptadine (a serotonin antagonist) is the recommended pharmacological treatment, typically starting with 12 mg orally, followed by 2 mg every 2 hours until symptoms improve, as described in the same study 1. Benzodiazepines like lorazepam or diazepam may be used for agitation, tremor, and hyperthermia.
Key Considerations
- Diphenhydramine has antihistamine and anticholinergic properties that can help with some symptoms like allergic reactions or extrapyramidal symptoms, but it does not directly antagonize serotonin receptors and therefore cannot effectively treat the underlying cause of serotonin syndrome.
- Using diphenhydramine might even worsen the condition by adding to the anticholinergic burden, potentially increasing agitation and hyperthermia, as anticholinergic syndrome can present with altered mental status, autonomic dysfunction, and neuromuscular abnormalities, similar to serotonin syndrome 1.
- The study highlights the importance of removing the precipitating agent and providing supportive care in all drug toxicity syndromes, including serotonin syndrome, and notes that specific therapy may differ depending on the disorder 1.
Treatment Approach
- Discontinue all serotonergic medications
- Provide supportive care, including treatment of agitation, hyperthermia, and autonomic instability
- Consider cyproheptadine for moderate to severe cases, as it is a serotonin antagonist that can directly address the underlying mechanism of serotonin syndrome 1
- Benzodiazepines may be used for agitation, tremor, and hyperthermia, but diphenhydramine is not recommended due to its potential to worsen the condition.
From the Research
Treatment of Serotonin Syndrome
- The treatment of serotonin syndrome typically involves withdrawal of the offending agent, aggressive supportive care, and occasionally the administration of serotonin antagonists such as cyproheptadine or chlorpromazine 2.
- There is no evidence to suggest that diphenhydramine is used to treat serotonin syndrome.
- Cyproheptadine has been shown to be effective in treating serotonin syndrome, with studies demonstrating its ability to resolve symptoms in patients with the condition 3, 2, 4, 5.
Serotonin Antagonists
- Cyproheptadine is a serotonin antagonist that has been used to treat serotonin syndrome, and its use should be considered an adjunct to supportive care 3.
- Chlorpromazine is another serotonin antagonist that may be used to treat serotonin syndrome, although its use is not as well-studied as cyproheptadine 2.
Delayed-Onset Serotonin Syndrome
- Delayed-onset serotonin syndrome can occur in patients who ingest a mixture of longer-acting serotonin agonists with serotonin antagonists, and clinicians should be aware of this possibility 4.
- In such cases, the onset of serotonin syndrome may be delayed, and patients may require prolonged monitoring and treatment.
Prevention and Management
- Prevention and management of serotonin syndrome involve identifying patients at risk, avoiding the use of serotonergic agents when possible, and monitoring patients closely for signs of the condition 2, 6, 5.
- Clinicians should be aware of the potential for serotonin syndrome when prescribing serotonergic agents, and patients should be educated on the risks and symptoms of the condition.