Serotonin syndrome is diagnosed clinically and requires a thorough review of medications and a careful physical exam. Symptoms tend to develop rapidly after exposure to the precipitating drug: 30% within one hour, 60% within 6 hours, and nearly all patients with toxicity developing symptoms within 24 hours of exposure.
It is noted that some cases of serotonin syndrome may be mild and go undiagnosed or they could be misdiagnosed, so the true occurrence may be higher. Additionally, because drugs other than SSRIs can cause serotonin syndrome, there are likely more yearly cases of serotonin syndrome than the survey found.
Serotonin is a chemical that the body produces naturally. It's needed for the nerve cells and brain to function. But too much serotonin causes signs and symptoms that can range from mild (shivering and diarrhea) to severe (muscle rigidity, fever and seizures).
Mild serotonin syndrome symptoms often includes the following: Shivering and tremors. Twitching or involuntary muscle movements. Excessive sweating.
To be diagnosed with serotonin syndrome, the person must have been taking a drug that changes the body's serotonin level (serotonergic drug) and have at least three of the following signs or symptoms: Agitation. Abnormal eye movements called 'ocular clonus' Heavy sweating not due to activity.
Neuroleptic Malignant Syndrome, which often times mimics serotonin syndrome, also develops over days to weeks [8,9]. Besides, in 70% of the patients, clinical signs including agitated delirium with confusion appear first, followed by tremors, rigidity, hyperthermia, profuse diaphoresis and tachypnoea [10-12].
Researchers also found that the incidence of serotonin syndrome was 0 to 4 cases per 10,000 person-years of exposure to coprescription of triptans and SSRI or SNRI antidepressants.
Mild serotonin syndrome may cause subtle symptoms, such as mild tremors, restlessness, or headaches. Signs of severe serotonin syndrome include rigid muscles, seizures, fever, and nausea or vomiting.
The hallmark signs and symptoms of serotonin syndrome are anxiety and restlessness, diaphoresis, mydriasis, clonus, hyperrflexia, tachycardia and hypertension. Treatment is mainly supportive care and includes intravenous fluids, benzodiazepines titrated to symptom control and blood pressure control as needed.
If the symptoms came on rapidly (within a few hours), think serotonin syndrome. If they came on gradually, over days to weeks, think NMS. Fever, agitation/confusion, tachycardia, and muscle rigidity are almost universally present with NMS but can be present in varying degrees with serotonin syndrome.
Signs that you are experiencing serotonin syndrome include: Mental status changes including anxiety, restlessness, delirium and disorientation. Neuromuscular problems including tremor, twitching, overactive reflexes, agitation and muscle rigidity.
About 7300 diagnosed cases of serotonin syndrome occur each year, and about 100 of these cases result in death. Drugs with serotoninergic properties have the ability to increase the level of serotonin or to act as direct agonists of postsynaptic serotonin receptors in the central nervous system (CNS).
It is important to note that symptoms of serotonin syndrome usually present within 6 to 8 hours of initiating or increasing serotonergic medications. The onset tends to be more acute than in a condition such as neuroleptic malignant syndrome, which shares some other features with serotonin toxicity.
Symptoms of serotonin syndrome and their severity vary from person to person. They can be mild to severe to even fatal. If you're taking a medication that affects serotonin and experience any of the following symptoms, call your healthcare provider or visit an urgent or emergency care facility right away.
Although SS typically develops rapidly after ingestion of serotonergic drugs, our observations suggest that a subset of patients may have mild and chronic forms. A diagnosis of SS is important even in mild and indolent form, as it is not supposed to resolve spontaneously as long as serotonergic drugs are administered.
Signs and symptoms include agitation, anxiety, restlessness, disorientation, diaphoresis, hyperthermia, tachycardia, nausea, vomiting, tremor, muscle rigidity, hyperreflexia, myoclonus, dilated pupils, ocular clonus, dry mucous membranes, flushed skin, increased bowel sounds, and a bilateral Babinski sign.
Most cases of serotonin syndrome present within 24 hours of a change or initiation of a serotonergic drug (table 2). Typical vital sign abnormalities include tachycardia and hypertension, but severe cases may develop hyperthermia and rapid, dramatic swings in pulse and blood pressure.
For mild serotonin syndrome, treatment involves discontinuing the offending agent and supportive therapy with intravenous fluids, correction of vital signs, and symptomatic treatment with a benzodiazepine. Patients should be admitted and observed for 12 to 24 hours to prevent exacerbation.
Untreated, serotonin syndrome can be deadly. With treatment, symptoms usually go away in less than 24 hours. Permanent organ damage may result, even with treatment.
Nonserotonergic antidepressants such as mirtazapine and bupropion are possible alternatives. Most tricyclic antidepressants (e.g., amitriptyline, desipramine and nortriptyline) are also less serotonergic than SSRIs, though clomipramine and imipramine are notable exceptions.
Chronic stress is known to affect serotonin (5HT) neurotransmission in the brain and to alter body temperature.
Patients with some anxiety disorders, including social anxiety, have been found to have higher, not lower, levels of serotonin. Some patients experience a temporary increase in anxiety when they begin SSRI and SNRI medications and serotonin levels go up.
If a patient notifies you of spontaneous clonus (involuntary muscle contractions) or new tremor and hyperreflexia (feeling twitchy), this is often a strong indication of serotonin syndrome and immediate referral to emergency services is recommended.
Preventing serotonin toxicity
Serotonin toxicity remains a confusing area for practitioners and can be a scary, potentially fatal experience for patients. As most cases are avoidable, learning to identify and prevent it is key.