Serotonin Syndrome

Page Created on 10th February 2020 by Tina Grant. Due for Review 10th February 2021.

Introduction

1. Serotonin Syndrome (SS) is a clinical manifestation of excess serotonin in the central nervous system, resulting from the therapeutic use or overdose of serotonergic drugs
2. Is a clinical diagnosis based on a triad of features (see below) and a history of exposure to a serotonergic drug
3. There is a spectrum of toxicity, ranging from mild to moderate to severe.
4. Diagnosis is clinical and should be based on the Hunter Serotonin Toxicity Criteria (below), of which clonus is a key diagnostic feature.
5. Treatment is guided by the severity of toxicity and involves cessation of the drug or drugs, supportive care, and anti-serotonergic drugs in selected patients.

Serotonin-Elevating Drugs

1. antidepressants eg SSRI, SNRI, TCA, MAOI, lithium, St John’s Wort.
2. analgesics eg tramadol, methadone, fentanyl.
3. anti-emetics eg ondansetron, metoclopramide
4. recreational eg cocaine, MDMA, amphetamines, LSD.
5. sumatriptan, used for migraine, is also a serotonin agonist

Triad of Clinical Features

1. Neuromuscular excitation: Clonus is the most common diagnostic feature. Hyperreflexia occurs almost universally in serotonin toxicity. Other symptoms include tremor and hypertonia.
2. Autonomic effects: sweating, hyperthermia and tachycardia.
3. Altered mental status: agitation, anxiety and confusion in severe toxicity.
4. Diagnosis should be based on the Hunter Serotonin Toxicity Criteria shown below.

Severity

1. Mild: patients are not usually distressed – they show features of hyperreflexia, inducible clonus and tremor.
2. Moderate: the patient is in significant distress. It is characterised by agitation and tachycardia plus features of mild toxicity as above.
3. Severe: this is a medical emergency and risks progression to multi-organ failure. Characterised by hyperthermia and hypertonia.

Differentials

1. Neuroleptic malignant syndrome: potentially life threatening complication of treatment with antipsychotic drugs or abrupt withdrawal of dopamine agonists, characterized by altered mental status, muscle rigidity autonomic disturbances, hyperthermia and significant increase in serum CK.
2. Sympathomimetic toxicity: exposure to sympathomimetics. Absence of neuromuscular excitation.
3. Anticholinergic delirium: normal reflexes, dry mouth, hot and dry skin, absent bowel sounds.
4. Malignant hyperthermia: caused by inhalational anaesthetics; mottled and patchily cyanotic skin, severe rigidity and hyporeflexia.
5. Other differentials to exclude are meningitis, encephalitis, non-convulsive status epilepticus and baclofen withdrawal.

Investigations

1. Diagnosis of serotonin toxicity is primarily clinical, and diagnostic tests are rarely required unless other differential diagnoses are being considered or to determine sequelae of illness.
2. Check U&Es and CK to assess for rhabdomyolysis and consequent renal impairment in severe toxicity.
3. Urine toxicology screen should be performed in patients with suspected co-ingestion of other drugs or illicit substances.

Management

1. In all cases, first stop any serotonergic drugs or interacting agents.
2. Mild toxicity: no treatment required. Toxicity usually resolves within 24hrs, although is dependent on the half life of the drug. Fluoxetine toxicity may take longer to resolve.
3. Moderate toxicity: observe in hospital for 6 hours and correct cardiovascular and thermal disturbances. Pharmacotherapy may be used to reduce distressing neuromuscular excitation and agitation.
4. Severe toxicity: transfer to CCU. Early intubation and ventilation recommended to prevent rhabdomyolysis. Treat hyperthermia aggressively with cooling and muscle paralysis.
5. Once SS has resolved try other drugs or restart low doses slowly, and rule out other contributing drugs such as OTC medications or illicit drugs.

Pharmacotherapy

1. For patients with neuromuscular excitation and agitation that is distressing or unpleasant, a single high dose of cyproheptadine (a non-specific 5-HT2 antagonist and antihistamine) may be used. Rx 12 mg orally as a single dose, may repeat once according to response; or 4-8 mg orally three times daily
2. Diazepam may be used for anxiety and sedation. Rx 5-10 mg orally as a single dose, may repeat in 30-60 minutes according to response
3. In severe SS, sedation and muscle paralysis is achieved with midazolam and morphine or with propofol.
4. Chlorpromazine can be used to treat hyperthermia and agitation.

Content created by Jon Macklin