From the Guidelines
Serotonin syndrome is a potentially life-threatening condition caused by excessive serotonin levels in the body, typically occurring when two or more medications that increase serotonin are taken together or at high doses. Common symptoms include:
- Agitation or restlessness
- Confusion
- Rapid heart rate and high blood pressure
- Dilated pupils
- Muscle rigidity or twitching
- Sweating
- Shivering
- Diarrhea Medications that can contribute to serotonin syndrome include:
- SSRIs (e.g., fluoxetine, sertraline) 1
- SNRIs (e.g., venlafaxine, duloxetine)
- Tricyclic antidepressants
- MAOIs
- Certain pain medications (e.g., tramadol)
- Some migraine medications
- St. John's Wort To prevent serotonin syndrome, always inform your doctor about all medications you're taking, including over-the-counter drugs and supplements. If you suspect serotonin syndrome, seek immediate medical attention. Treatment typically involves stopping the offending medications and providing supportive care, which may include treatment of agitation, amelioration of hyperthermia, and management of autonomic instability 1.
Serotonin syndrome occurs because these medications increase the availability of serotonin in the brain and body. When levels become too high, it can lead to overstimulation of serotonin receptors, causing the characteristic symptoms. The condition can be triggered when serotonergic medications are combined, and symptoms can arise within 24 to 48 hours after combining medications 1. Advanced symptoms include fever, seizures, arrhythmias, and unconsciousness, which can lead to fatalities. The mortality rate is approximately 11%, with significant morbidity and mortality associated with serotonin syndrome 1.
Clinical diagnostic criteria for serotonin syndrome have been proposed, with Hunter criteria being most commonly used 1. Treatment considerations include discontinuing the precipitant drug, supportive care, and benzodiazepine for agitation. In severe cases, serotonin2A antagonists (e.g., cyproheptadine) may be considered 1. It is essential to exercise caution when combining two or more non-MAOI serotonergic drugs, including antidepressants, opioids, and other pain medications, stimulants, cough/cold/allergy medications, and other over-the-counter medications 1.
From the FDA Drug Label
Serotonin Syndrome — The development of a potentially life–threatening serotonin syndrome may occur with SNRIs and SSRIs, including Prozac treatment, particularly with concomitant use of serotonergic drugs (including triptans) and with drugs which impair metabolism of serotonin (including MAOIs). Serotonin syndrome symptoms may include mental status changes (e.g., agitation, hallucinations, coma), autonomic instability (e.g., tachycardia, labile blood pressure, hyperthermia), neuromuscular aberrations (e.g., hyperreflexia, incoordination) and/or gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea).
Serotonin syndrome is a rare but serious problem that can happen in people using sumatriptan tablets, especially if sumatriptan tablets are used with anti-depressant medicines called SSRIs or SNRIs Call your healthcare provider right away if you have any of the following symptoms of serotonin syndrome: mental changes such as seeing things that are not there (hallucinations), agitation, or coma fast heartbeat changes in blood pressure high body temperature tight muscles trouble walking seizures.
Serotonin syndrome is a potentially life-threatening condition that can occur with the use of certain medications, including SSRIs and SNRIs, particularly when used in combination with other serotonergic drugs or drugs that impair serotonin metabolism.
- Symptoms of serotonin syndrome may include:
- Mental status changes (e.g., agitation, hallucinations, coma)
- Autonomic instability (e.g., tachycardia, labile blood pressure, hyperthermia)
- Neuromuscular aberrations (e.g., hyperreflexia, incoordination)
- Gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea)
- Mental changes such as seeing things that are not there (hallucinations), agitation, or coma
- Fast heartbeat
- Changes in blood pressure
- High body temperature
- Tight muscles
- Trouble walking
- Seizures It is essential to seek medical attention immediately if any of these symptoms occur 2, 3, 4.
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 5.
- It can occur after the use of serotonergic agents alone or in combination with monoamine oxidase inhibitors 5, 6.
- The syndrome can also be precipitated by the initiation of a single serotonergic drug in a susceptible individual, the addition of a second or third agent to long-standing doses of a maintenance serotonergic drug, or after an overdose 6.
Clinical Features of Serotonin Syndrome
- SS classically consists of a triad of signs and symptoms broadly characterized as alteration of mental status, abnormalities of neuromuscular tone, and autonomic hyperactivity 5.
- Clinical manifestations are diverse and nonspecific, which may lead to misdiagnosis 5.
- The syndrome can range in severity from mild to life-threatening, with most cases being mild and resolving with prompt recognition and supportive care 5.
Management and Prevention of Serotonin Syndrome
- 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 5.
- Patients with moderate and severe cases of SS require inpatient hospitalization 5.
- Increased awareness of SS among psychiatrists, clinicians, and general practitioners is crucial due to the current increase in the use of serotonergic agents in clinical practice 5.
- SS is a manifestation of adverse pharmacology, making it predictable and highly preventable 5.
Diagnosis and Treatment
- Diagnosis of SS can be made using Hunter's criteria 7.
- Treatment includes discontinuation of all serotonergic medications and supportive therapy such as IV fluids, lorazepam, and cyproheptadine 7.
- Clinicians should be aware of the risk factors and clinical features of SS to improve identification and treatment of patients who present with the condition 8.