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The addition of trazodone to lurasidone and valproic acid can precipitate serotonin syndrome.

A patient developed probable serotonin syndrome (SS) within hours of adding 100 mg trazodone to a regimen including lurasidone and valproic acid. Symptoms included chills, nausea, sweating, dizziness, muscle stiffness, and tremor, which resolved over 48 hours. The case suggests that this drug combination can cause excessive serotoninergic activity via multiple mechanisms.

Last updated: Jul 26, 2026•0 RCTs•📖 Read as article →

Evidence Score

Evidence Score32/100
Human RCT☆☆☆☆☆
Meta-analysis☆☆☆☆☆
Mechanism★★★★★
Safety★★★★☆
Confidencelow

Study Evidence

Study 1. Probable Serotonin Syndrome Precipitated by the Addition of Trazodone to Lurasidone and Valproic Acid: A Case Report.

observational

Do A, Kachichian R, Vincent P · Sante mentale au Quebec (2026)

Participants: 1
Duration: 48 hours
Intervention: Addition of 100 mg trazodone to existing medications (lurasidone, valproic acid, estradiol, dexlansoprazole, spironolactone)
Outcome: Occurrence of serotonin syndrome symptoms (chills, nausea, sweating, dizziness, generalized muscle stiffness, tremor) and meeting Sternbach criteria for SS
Effect Size: N/A
Population: A single patient (case report) with insomnia, on a medication regimen including lurasidone and valproic acid

Result: A patient developed probable serotonin syndrome (SS) within hours of adding 100 mg trazodone to a regimen including lurasidone and valproic acid. Symptoms included chills, nausea, sweating, dizziness, muscle stiffness, and tremor, which resolved over 48 hours. The case suggests that this drug combination can cause excessive serotoninergic activity via multiple mechanisms.

PubMed: 42490704

Mechanism Graph

Trazodone inhibits serotonin reuptake
↓
Lurasidone acts as a 5-HT1A partial agonist
↓
Valproic acid may increase central serotoninergic neurotransmission
↓
Result: Excessive serotoninergic activity leading to serotonin syndrome

Limitations

  • ⚠No physical examination or laboratory tests were performed when the patient was symptomatic
  • ⚠Single case report with no control group, limiting generalizability
  • ⚠Potential confounding from other medications (estradiol, dexlansoprazole, spironolactone)

Frequently Asked Questions

What is serotonin syndrome?▼

Serotonin syndrome is a serious condition caused by excessive serotonin receptor activation, characterized by altered mental status, autonomic instability, and neuromuscular abnormalities.

Can trazodone alone cause serotonin syndrome?▼

Trazodone alone is less likely to cause serotonin syndrome; it is often associated with combinations of serotonergic drugs, such as SSRIs or other agents like lurasidone and valproic acid.

What medications were involved in this case?▼

The patient was taking trazodone, lurasidone, valproic acid, estradiol, dexlansoprazole, and spironolactone. The addition of trazodone was suspected as the trigger.

How long did the symptoms last?▼

Symptoms began a few hours after taking trazodone and gradually subsided over the next 48 hours.

Products

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References

  1. 1.Do A, Kachichian R, Vincent P. "Probable Serotonin Syndrome Precipitated by the Addition of Trazodone to Lurasidone and Valproic Acid: A Case Report.." Sante mentale au Quebec, 2026. PMID: 42490704
Disclaimer: This content is for educational purposes only and is not medical advice. Evidence scores reflect the quality and quantity of available research, not clinical recommendations. Always consult a healthcare professional before starting any supplement or intervention.