Serotonin syndrome

Overview

Serotonin syndrome is a potentially life-threatening condition resulting from an excess of serotonin in the central nervous system. It typically occurs due to the use or interaction of medications that increase serotonergic activity, particularly antidepressants. Serotonin is a neurotransmitter that plays a key role in regulating mood, digestion, sleep, and other bodily functions. When its levels become excessively elevated, it can overstimulate the nervous system, leading to a range of symptoms that can range from mild to severe. If not recognized and treated promptly, serotonin syndrome can lead to serious complications, including seizures, arrhythmias, and death.

Causes

Serotonin syndrome is most often triggered by the use of one or more drugs that affect serotonin levels. It can result from an overdose, a new medication, a dose increase, or a drug interaction. Common causes include:

• Selective serotonin reuptake inhibitors (SSRIs): e.g., fluoxetine, sertraline, citalopram

• Serotonin-norepinephrine reuptake inhibitors (SNRIs): e.g., venlafaxine, duloxetine

• Monoamine oxidase inhibitors (MAOIs): e.g., phenelzine, tranylcypromine

• Tricyclic antidepressants (TCAs): e.g., amitriptyline, clomipramine

• Triptans: used for migraines, e.g., sumatriptan

• Opioids: especially tramadol, fentanyl, and meperidine

• Illicit drugs: such as MDMA (ecstasy), LSD, and cocaine

• Herbal supplements: such as St. John's wort and ginseng

Combining these substances, particularly MAOIs with SSRIs or SNRIs, significantly increases the risk. Even therapeutic doses of a single serotonergic drug can sometimes cause the syndrome in sensitive individuals.

Symptoms

Symptoms of serotonin syndrome typically appear within hours of drug ingestion or dosage change. The syndrome manifests with a triad of symptoms involving autonomic, neuromuscular, and mental status changes:

Autonomic Symptoms:

• Hyperthermia (elevated body temperature)

• Tachycardia (rapid heart rate)

• Hypertension (high blood pressure)

• Diaphoresis (excessive sweating)

• Shivering

• Diarrhea

Neuromuscular Symptoms:

• Hyperreflexia (exaggerated reflexes)

• Clonus (involuntary, rhythmic muscle contractions)

• Tremors

• Muscle rigidity, especially in the lower limbs

• Myoclonus (muscle jerks)

Mental Status Changes:

• Agitation

• Confusion or delirium

• Restlessness

• Hallucinations in severe cases

Symptoms can progress rapidly, and severe cases may involve seizures, arrhythmias, rhabdomyolysis, respiratory failure, or coma.

Diagnosis

Diagnosis of serotonin syndrome is clinical, based on patient history, symptom presentation, and exclusion of other conditions. There is no definitive laboratory test for serotonin syndrome.

• History: Recent use or combination of serotonergic drugs is key

• Physical examination: Presence of hyperreflexia, clonus, tremor, and autonomic instability

• Hunter Serotonin Toxicity Criteria: A commonly used diagnostic tool that helps identify serotonin syndrome based on specific physical signs in patients with serotonergic agent exposure

• Rule out differential diagnoses: Conditions such as neuroleptic malignant syndrome (NMS), anticholinergic toxicity, malignant hyperthermia, or sepsis should be excluded

Treatment

Immediate recognition and management are essential for a good outcome. Treatment focuses on discontinuing the offending agents and providing supportive care:

Initial Management:

• Stop all serotonergic medications

• Hospitalization and monitoring of vital signs, especially in moderate to severe cases

• IV fluids for hydration and to manage hyperthermia

• Cooling measures for high fever (e.g., ice packs, cooling blankets)

Medications:

• Benzodiazepines: Such as diazepam or lorazepam to control agitation, tremors, and seizures

• Cyproheptadine: A serotonin antagonist that may be used orally or via nasogastric tube in moderate to severe cases

• Antihypertensives: To manage elevated blood pressure if needed

Advanced Support:

• Intubation and mechanical ventilation in severe cases with respiratory compromise

• ICU admission for severe hyperthermia or complications such as rhabdomyolysis

Prognosis

The prognosis of serotonin syndrome is generally favorable if recognized early and treated promptly. Most patients experience complete recovery within 24 to 72 hours after stopping the offending agent and receiving appropriate care. Mild cases may resolve with minimal intervention, while moderate to severe cases require hospitalization and intensive management.

Delayed treatment or unrecognized severe serotonin syndrome can result in serious complications or death. Education on drug interactions, especially when prescribing serotonergic agents, is crucial for prevention. Patients with a history of serotonin syndrome should avoid all drugs that can increase serotonin levels unless carefully monitored by a healthcare provider.