Fluoxetine-induced tricyclic toxicity: extent and duration

Combined fluoxetine-tricyclic medication has been recommended for patients who are partial responders or nonresponders to tricyclic medication alone. Three cases were encountered in which the addition of fluoxetine to tricyclic medication resulted in toxic, potentially dangerous elevations in tricyclic blood level, amounting to approximately 100-300% increases over recent tricyclic levels. In reducing the tricyclic dosage after fluoxetine, blood level decreases were behind dosage decreases; and blood level and dosage decreases were not well correlated with each other. Symptoms associated with toxic levels are described. Due to the long half-life of fluoxetine, such increases in tricyclic medication must be anticipated well in advance of initiating treatment with these two compounds. Based on these few cases, a procedure is tentatively recommended for patients on combined fluoxetine-tricyclic regimens, until such time as a definitive regimen can be developed.
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