Can Seroquel (quetiapine) cause serotonin syndrome?

Quetiapine (Seroquel) Can Cause Serotonin Syndrome

Yes, Seroquel (quetiapine) can cause serotonin syndrome, particularly when combined with other serotonergic medications. 1

Mechanism and Risk Factors

• Serotonin syndrome is caused by excess serotonin availability in the central nervous system, primarily affecting 5-HT1A receptors, with possible interactions with dopamine and 5-HT2 receptors 2
• While quetiapine alone has a lower risk of causing serotonin syndrome than other medications, it can contribute to this condition, especially when combined with other serotonergic agents like SSRIs (e.g., paroxetine) 1
• The risk significantly increases with medication combinations rather than with quetiapine monotherapy 3

Clinical Presentation

• Serotonin syndrome typically presents with a triad of symptoms: mental status changes, neuromuscular hyperactivity, and autonomic instability 4, 3
• The most common clinical finding is myoclonus, occurring in approximately 57% of cases 4
• Clonus and hyperreflexia are considered highly diagnostic for serotonin syndrome when they occur in the setting of serotonergic drug use 4
• Symptoms usually develop within 24-48 hours after combining serotonergic medications or changing dosages 3, 5

Diagnostic Criteria

• Hunter criteria are most commonly used for diagnosis of serotonin syndrome 4
• Diagnosis requires a high degree of clinical suspicion and is often a diagnosis of exclusion 1
• There are no pathognomonic laboratory or radiographic findings specific to serotonin syndrome 4

Severity and Complications

• Severe cases of serotonin syndrome are characterized by:
  • Hyperthermia (temperature >41.1°C)
  • Rhabdomyolysis with elevated creatine kinase
  • Metabolic acidosis
  • Elevated serum aminotransferase
  • Renal failure
  • Seizures
  • Disseminated intravascular coagulopathy 4
• The mortality rate is approximately 11%, indicating significant risk 4

Management

• First-line treatment involves immediate discontinuation of all serotonergic agents, including quetiapine if it's suspected to be contributing 4, 3
• Supportive care is essential, including:
  • Benzodiazepines for agitation and tremor 4, 3
  • IV fluids for autonomic instability 4, 3
  • External cooling for hyperthermia 4
  • Continuous cardiac monitoring 3
• In severe cases, emergency sedation, neuromuscular paralysis, and intubation may be necessary 4
• Approximately 25% of patients require intubation, mechanical ventilation, and ICU admission 4
• Serotonin antagonists such as cyproheptadine may be considered, especially in severe cases 4, 3
• Physical restraints should be avoided as they may exacerbate isometric contractions, worsening hyperthermia and lactic acidosis 4

Documented Cases and Evidence

• Case reports have documented serotonin syndrome occurring with quetiapine in combination with paroxetine (an SSRI) 1
• Serotonin syndrome can occur even without recent medication changes or dosage increases in susceptible individuals 1
• The condition has been reported with various medication combinations, including those involving atypical antipsychotics like quetiapine 5, 1

Prevention and Risk Mitigation

• Use caution when prescribing quetiapine alongside other serotonergic medications, particularly:
  • SSRIs (fluoxetine, paroxetine, sertraline, citalopram, escitalopram)
  • SNRIs (venlafaxine, duloxetine)
  • MAOIs
  • Opioids (particularly tramadol, meperidine, methadone, fentanyl)
  • Triptans
  • St. John's Wort 3
• Start with low doses when adding a second serotonergic medication to an existing regimen 3
• Monitor closely for early signs of serotonin syndrome, especially during the first 24-48 hours after medication changes 3
• Consider patient-specific risk factors such as age, medication dosages, and concomitant use of CYP2D6 inhibitors 3