Drug Interaction Report

MONITOR: Coadministration of quetiapine with drugs that possess serotonergic activity (e.g., selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), monoamine oxidase inhibitors (MAOIs), tricyclic antidepressants (TCAs), etc.) may increase the risk of serotonin syndrome, a rare but serious and potentially fatal condition. Combining quetiapine with other serotonergic drugs may increase the risk of serotonin syndrome by relatively enhancing 5-HT1A receptor activity. However, data are currently limited to case reports. In one case report, an 85-year-old woman developed serotonin syndrome within hours of increasing quetiapine from 12.5 mg to 25 mg/day while also taking escitalopram, mirtazapine, sulpiride, and olanzapine; symptoms resolved within 48 hours after the discontinuation of all serotonergic medications. Symptoms of serotonin syndrome may include mental status changes such as irritability, altered consciousness, confusion, hallucination, and coma; autonomic dysfunction such as tachycardia, hyperthermia, diaphoresis, shivering, blood pressure lability, and mydriasis; neuromuscular abnormalities such as hyperreflexia, myoclonus, tremor, rigidity, and ataxia; and gastrointestinal symptoms such as abdominal cramping, nausea, vomiting, and diarrhea. In addition, central nervous system- and/or respiratory-depressant effects may be additively or synergistically increased in patients taking multiple drugs that also cause these effects (e.g., buspirone, desvenlafaxine, dextromethorphan, mianserin, reboxetine).

MANAGEMENT: Some authorities advise caution and closer monitoring for serotonin syndrome when quetiapine is coadministered with other serotonergic agents, especially during initiation and dose escalations. Patients should be instructed to promptly notify their healthcare provider if they experience symptoms of serotonin syndrome. If serotonin syndrome is suspected, a dose reduction or discontinuation of therapy should be considered depending on the severity of the symptoms. If serotonin syndrome develops during therapy, all serotonergic agents should be discontinued immediately, and supportive care rendered as necessary. Due to variability and occasionally prolonged half-lives of these coadministered agents, consulting individual product labeling for specific guidance is advised.