Drug Interaction Report

MONITOR: The coadministration of low-dose trazodone and ginkgo biloba was associated with the development of ataxia, drowsiness, and coma in an elderly patient with Alzheimer's disease. The patient had received a total of 100 mg trazodone and 320 mg ginkgo biloba in an approximately 50-hour period. The effects were reversed by flumazenil. The mechanism of interaction proposed by the investigators is a synergistic GABAergic effect due to partial agonistic action of ginkgo biloba at benzodiazepine binding sites and increased liberation of GABA by an active metabolite of trazodone. Ginkgo may also induce the metabolism of trazodone to this active metabolite. However, causality was not clearly determined due to the presence of a benzodiazepine, which had been discontinued the day before the trazodone was initiated.

MANAGEMENT: In general, patients should consult a healthcare provider before taking any herbal or alternative medicine. Caution may be appropriate when combining ginkgo products with trazodone, especially in the elderly. Patients should be advised of the potential for increased sedation or other central nervous system effects.

GENERALLY AVOID: Alcohol may potentiate some of the pharmacologic effects of CNS-active agents. Use in combination may result in additive central nervous system depression and/or impairment of judgment, thinking, and psychomotor skills.

MANAGEMENT: Patients receiving CNS-active agents should be warned of this interaction and advised to avoid or limit consumption of alcohol. Ambulatory patients should be counseled to avoid hazardous activities requiring complete mental alertness and motor coordination until they know how these agents affect them, and to notify their physician if they experience excessive or prolonged CNS effects that interfere with their normal activities.