Can quetiapine (antipsychotic medication) overdose cause serotonin syndrome (serotonin toxicity)?

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Last updated: May 4, 2025 • View editorial policy

From the Guidelines

Quetiapine overdose typically does not cause serotonin toxicity, but it can increase the risk of serotonin syndrome when taken in combination with other serotonergic medications. Quetiapine is an atypical antipsychotic that primarily affects dopamine and histamine receptors rather than serotonin. While quetiapine does have some mild serotonergic effects, these are generally not potent enough to cause serotonin syndrome even in overdose situations, as noted in studies such as 1. The main concerns with quetiapine overdose include sedation, hypotension, tachycardia, QT prolongation, and in severe cases, respiratory depression or coma.

Some key points to consider in the management of quetiapine overdose include:

  • The risk of serotonin syndrome is higher when quetiapine is combined with other serotonergic medications, such as SSRIs, SNRIs, MAOIs, or certain pain medications like tramadol, as discussed in 1 and 2.
  • Treatment of quetiapine overdose typically involves supportive care, including monitoring of vital signs and management of symptoms such as agitation and hyperthermia, as outlined in 3 and 4.
  • In severe cases, patients may require intensive care unit admission and treatment with medications such as benzodiazepines or serotonin2A antagonists, as noted in 2.

It's worth noting that the risk of serotonin syndrome can be increased when quetiapine is taken in combination with other serotonergic medications, and that patients who have overdosed on quetiapine should seek immediate medical attention regardless of the specific symptoms, as any drug overdose can be potentially life-threatening, as emphasized in 1 and 2.

From the Research

Quetiapine Overdose and Serotonin Toxicity

  • Quetiapine overdose can lead to serotonin toxicity, also known as serotonin syndrome, especially when combined with other serotonergic agents 5, 6.
  • A case study reported that an 85-year-old woman developed serotonin syndrome after increasing her quetiapine dose from 12.5mg to 25mg per day, highlighting the risk of serotonin toxicity even with small dose increases 5.
  • Another case study described a 70-year-old woman who presented with confusion and muscle spasms due to serotonin toxicity associated with paroxetine and quetiapine treatment, emphasizing the importance of clinical suspicion in diagnosing serotonin toxicity 6.

Clinical Features and Management

  • Quetiapine overdose can cause central nervous system depression, sinus tachycardia, and prolonged QTc interval 7, 8.
  • Management of quetiapine overdose includes activated charcoal, intravenous saline, and intubation for airway protection, as well as discontinuation of the offending agent and administration of benzodiazepines and cyproheptadine in some cases 7, 8, 9.
  • The use of cyproheptadine in serotonin syndrome cases is uncertain and questionable, with no significant differences in serious outcomes or hospitalization rates observed in patients who received cyproheptadine compared to those who did not 9.

Risk Factors and Outcomes

  • Combining quetiapine with other serotonergic agents increases the risk of serotonin toxicity 5, 6.
  • Large overdoses of quetiapine may require intubation and ventilation for associated respiratory depression, and patients may experience seizures, delirium, and mechanical ventilation 8.
  • Reported dose and peak quetiapine concentrations are significantly associated with ICU admission and length of stay more than 24 hours 8.

References

Guideline

clinical practice guideline for the assessment and treatment of children and adolescents with anxiety disorders.

Journal of the American Academy of Child and Adolescent Psychiatry, 2020

Research

Serotonin Syndrome Triggered by Increasing the Dose of Quetiapine.

Clinical practice and cases in emergency medicine, 2021

Research

Acute quetiapine poisoning.

The Journal of emergency medicine, 1999

Research

Quetiapine poisoning: a case series.

Annals of emergency medicine, 2003

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.