Serotonin Syndrome Causes, Symptoms and Diagnosis

Serotonin is a neurotransmitter. It is found in the digestive system, blood platelets, and throughout the CNS. Serotonin is associated with uplifting mood and preventing anxiety or depression.

Serotonin syndrome is a deadly condition caused by elevated serotonin concentration. Serotonin syndrome also known as serotonin storm can occur due to the use of either a single serotonergic drug or as a result of drug interaction between two or more different serotonergic drugs.

New medications or increased dosage of previously used medicines can hike up serotonin levels in the body. Illicit drugs and dietary supplements are sometimes associated with serotonin syndrome. Higher levels of serotonin in the body can cause affect muscles and various other parts.

Mild forms of serotonin syndrome can diminish within a day of stopping the medicines or sometimes after taking drugs that block serotonin. Serotonin syndrome ends in death if quick treatment is not received.

What Are the Symptoms of Serotonin Syndrome?

Serotonin syndrome symptoms usually occur within 24 hours of taking a new drug or increasing the dose of a drug you are already taking. The symptoms are often described as a clinical triad of abnormalities. Signs and symptoms include mild to moderate serotonin syndrome:

1. Agitation or Restlessness

2. Mental Confusion

3. Hallucinations

4. Rapid Heart Rate (Tachycardia)

5. High Blood Pressure ( Hypertension)

6. Dilated Pupils

7. Loss of Muscle Coordination and Twitching of Muscles (Myoclonus)

8. Muscle Rigidity

9. Heavy Sweating

10. Diarrhea

11. Hyperactive Bwel Sounds

12. Horizontal Ocular Clonus

13. Hypervigilance

14. Pressured Speech

15. Headache

16. Shivering

17. Goosebumps

18. High Body Temperature (Hyperthermia)

19. Hyperreflexia

20. Delirium

Signs and symptoms of severe serotonin syndrome:

1. Seizures

2. Myoglobinuria

3. Uneven Heartbeat

4. Metabolic acidosis

5. Renal Failure

6. Rhabdomyolysis

7. Respiratory Failure

8. Respiratory Distress Syndrome

9. Intravascular Clotting

10. Coma

11. Death

What are the Causes of Serotonin Syndrome?

Serotonin syndrome is also known as serotonin toxicity is caused when hyperactivation of both the peripheral and central postsynaptic 5-HT 1A and 5-HT 2A receptors occurs.

Excessive accumulation of serotonin creates the symptoms of serotonin syndrome. It is possible that just one drug can increase serotonin levels but mostly serotonin syndrome occurs due to a combination of medicines.

How is Serotonin Syndrome Diagnosed?

A single diagnostic test cannot confirm this syndrome. The diagnostic gold standard for serotonin syndrome is a diagnosis by a medical toxicologist.

Diagnosis for serotonin syndrome is entirely based on the history of the patient’s use of a serotonergic drug or any dietary supplement or illicit substances or any recent changes in medication dosing or addition of new drugs to their original drug regimen. The onset of symptoms and the presence of any comorbidities are of utmost importance.

A doctor might alert himself with the use of drugs for depression and chronic pain which can precipitate serotonin syndrome. Most incidences of serotonin syndrome were reported in patients with end-stage renal disease who are on Selective serotonin reuptake inhibitor (SSRIs) and hemodialysis.

Identifying serotonin syndrome is possible only when other conditions are ruled out since the symptoms coincide with the neuroleptic malignant syndrome (NMS), malignant hyperthermia, meningitis, encephalitis, heatstroke, and central hyperthermia. An integral part for diagnosing serotonin syndrome is the neurological examination.

Clonus and hyperreflexia are most important for the diagnosis of serotonin syndrome but severe muscle rigidity may mask the symptoms.

Some nonspecific laboratory abnormalities that may be seen in serotonin syndrome: Leukocytosis, low bicarbonate level, elevated creatinine level, and elevated transaminases. Serum serotonin concentrations cannot correctly determine the severity of serotonin syndrome.

Tests that the doctor may include:

1. Blood Culturing (to check for infection)

2. Complete Blood Count (CBC)

3. Blood Test to check Electrolyte Balance

4. Urine Test for Drug and Alcohol Screening

5. Kidney and Liver Function Test

6. Thyroid Function Test

7. Computed Tomography (CT) of the Brain

8. Electrocardiogram (ECG) of the Heart

9. Lumbar Puncture(spinal tap) to Evaluate your Spinal Fluid

10. Chest X-Ray

What are the Treatments for Serotonin Syndrome?

Once detected, the first line of treatment for serotonin syndrome would be discontinuing all serotonergic agents, providing oxygen to keep oxygen saturation above 93%, administrating intravenous fluid, monitoring cardiac signals, therapeutically using benzodiazepines, and administering serotonin antagonist, Cyproheptadine (Periactin).

Treatment for mild to moderate cases includes discontinuation of serotonergic agent, using benzodiazepines, and administration of serotonin antagonist alongside observation for at least 6 -24 hours. In severe cases, patients should be treated as above along with paralysis of muscles and ventilation in the ICU.

What are the Complications Associated with Serotonin Syndrome?

Uncontrollable muscle spasms often lead to muscle damage and loss(rhabdomyolysis). Muscles break down into myoglobin which in turn breaks into components that filter out through the kidney.

These components can damage kidney cells. A quick treatment for serotonin syndrome is necessary to prevent renal failure.


There is no way to predict who will develop serotonin syndrome. The best way to prevent this syndrome is to avoid multi serotonergic regimens. Close monitoring should be provided to patients who consume 1 or more serotonergic drugs. Early recognition and treatment of serotonin syndrome can significantly prevent morbidity and mortality.

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