Makindo Medical Notes

Serotonin syndrome is a potentially life-threatening drug-induced condition caused by an excess of serotonin (5-Hydroxytryptamine). It commonly occurs soon after starting serotonergic medications, increasing the dose, or after an overdose. The risk is significantly heightened when serotonergic drugs are combined with Monoamine Oxidase Inhibitors (MAOIs), especially MAO-A inhibitors that preferentially inhibit the metabolism of serotonin.

Aetiology

• Serotonin (5-hydroxytryptamine, or 5-HT) is a neurotransmitter primarily found in the brain, gastrointestinal tract, and blood platelets. It plays a vital role in regulating mood, anxiety, and happiness, as well as several physiological processes such as sleep, appetite, and digestion.
• In the central nervous system (CNS), serotonin modulates cognitive functions, while in the peripheral nervous system (PNS), it influences smooth muscle contraction, vasoconstriction, and gastrointestinal motility.
• An excess of serotonin in these systems can lead to hyperstimulation, resulting in the characteristic symptoms of serotonin syndrome, such as increased muscle tone, autonomic instability, and mental status changes.

Causes

• Antidepressants: MAOIs, TCAs, SSRIs, SNRIs, trazodone, mirtazapine.
• Opiates: Pethidine, fentanyl, buprenorphine, oxycodone, tramadol.
• CNS Stimulants: MDMA, phentermine, amphetamines, sibutramine, methamphetamine, cocaine.
• Herbs: St John's Wort, ginseng, nutmeg.
• Other Drugs: Valproate, buspirone, lithium, linezolid, chlorpheniramine, risperidone, olanzapine, ondansetron, granisetron, metoclopramide.

Clinical Features

• Inducible or ocular clonus with agitation or diaphoresis
• Tachycardia, shivering, sweating, mydriasis, diarrhoea
• Myoclonic jerks, hyperreflexia, clonus, hyperthermia
• Increased vigilance and agitation, metabolic acidosis
• Rhabdomyolysis, Disseminated Intravascular Coagulation (DIC), Acute Kidney Injury (AKI), seizures

Investigations

• Full Blood Count (FBC), Urea & Electrolytes (U&E), Liver Function Tests (LFTs), C-Reactive Protein (CRP), Creatine Kinase (CK), Lactate, Glucose, Arterial Blood Gas (ABG)
• 12-lead ECG, Chest X-ray (CXR)
• Consider CT head and Lumbar Puncture/CSF analysis if encephalitis or HSV is suspected

Management: Early expert consultation is essential for severe cases.

• Initial steps: Ensure airway, breathing, and circulation (ABC). Consider High Dependency Unit (HDU) if the patient has low Glasgow Coma Scale (GCS), hyperthermia (>40°C), AKI, or seizures.
• Medication management: Stop serotonergic drugs to usually achieve rapid improvement.
• Seizure and agitation control: Administer IV diazepam (5-10 mg) to reduce seizures and muscle tone.
• Temperature management: Aggressive cooling if the temperature exceeds 40°C.
• Fluid management: IV fluids (1-2 litres or as needed) to maintain hydration and support the cardiovascular system.
• Monitoring: Watch for electrolyte imbalances (U&E, potassium), CK levels, lactate, and ABG for metabolic disturbances.

Other Specific Treatments

• For agitation or muscle rigidity: Diazepam 10 mg IV, can be repeated as needed. Large doses may be required in severe cases.
• Serotonin antagonists: Cyproheptadine 12 mg PO/NG stat, then 8 mg every 6 hours.
• Additional options: Chlorpromazine 25 mg IM, Dantrolene 1-2.5 mg/kg (up to a max of 10 mg/kg) for hyperthermia or severe muscle rigidity.
• If rhabdomyolysis: Consider 1.26% bicarbonate therapy to prevent renal damage.
• For hypoglycaemia: Administer IV glucose (10%) as needed.
• Once the causative drug is discontinued, symptoms generally resolve. Avoid the use of opiates with intrinsic serotonergic activity.

References

• Guidelines for the Management of Serotonin Syndrome
• Serotonin Syndrome: Pathophysiology, Clinical Features, Management, and Potential Future Directions