Saffron and Seroquel (Quetiapine) Interaction
Saffron should be used with caution when combined with Seroquel (quetiapine) due to the theoretical risk of serotonin syndrome, though this interaction is not well-documented in clinical practice. The primary concern stems from saffron's serotonergic activity combined with quetiapine's effects on multiple neurotransmitter systems.
Mechanism of Concern
The theoretical interaction involves serotonin syndrome risk, which occurs when multiple serotonergic agents are combined. 1
Serotonin syndrome is characterized by mental status changes (confusion, agitation, anxiety), neuromuscular hyperactivity (tremors, clonus, hyperreflexia), and autonomic hyperactivity (hypertension, tachycardia, diaphoresis) that can develop within 24-48 hours of combining serotonergic medications. 1
Saffron has demonstrated serotonergic activity in multiple clinical trials, showing antidepressant effects comparable to SSRIs like fluoxetine and citalopram. 2
Quetiapine interacts with multiple neurotransmitter receptors, including serotonin (5-HT2A) receptors, though it has higher affinity for these compared to dopamine receptors. 3
Clinical Evidence and Risk Assessment
The actual clinical risk appears low based on available evidence, but formal drug interaction studies between saffron and quetiapine have not been conducted.
Saffron has been safely combined with SSRIs (fluoxetine) in clinical trials without reports of serotonin syndrome, suggesting the serotonergic effect may be modest. 4, 5
One guideline notes caution when quetiapine is combined with drugs that have narrow therapeutic indices, particularly in the context of hepatitis C treatment regimens that inhibit CYP3A4. 1
However, a study by Safarinejad et al. (2011) reported adverse hematological reactions in a large number of patients treated with saffron (Crocus sativus Linn), indicating that saffron is not without potential toxicity at certain doses. 1
Practical Recommendations
Monitor closely for early signs of serotonin syndrome if combining these agents, particularly in the first 24-48 hours after starting saffron or increasing its dose. 1
Start saffron at the lowest effective dose (typically 15-30 mg daily) if combining with quetiapine. 4, 5
Watch for symptoms including confusion, agitation, tremors, hyperreflexia, tachycardia, or diaphoresis. 1
Consider the perioperative guideline recommendation to hold saffron for 2 weeks before surgery due to concerns about CNS effects and bleeding risk, which suggests caution with CNS-active medications generally. 1
Important Caveats
The lack of formal pharmacokinetic studies between saffron and quetiapine means the interaction profile is incompletely characterized. 1
Most psychoactive drug combinations with newer agents lack formal interaction studies, requiring clinical vigilance. 1
Saffron's effects on cytochrome P450 enzymes and drug transporters have not been fully elucidated, making prediction of interactions difficult. 1
The dose of saffron matters significantly—therapeutic doses (30 mg/day) used in depression trials appear safer than higher doses that have caused hematological toxicity. 1, 4