Sir:We report 2 cases in which concomitant use of a selective serotonin reuptake inhibitor (SSRI), sertraline, and an antiseizure/ mood-stabilizing drug, carbamazepine, resulted in a lack of sertraline efficacy at doses 2 to 4 times higher than the minimum effective dose of sertraline, 50 mg/day, under steady-state dosing conditions. This is the first published report of such a reduction. Case 1. Ms. A, a 33-year-old, physically active white woman with a diagnosis of schizoaffective disorder (bipolar type), had been successfully treated by a combination of haloperidol, 4-6 mg/day, and carbamazepine, 1000 mg/day, for 3 years. When she then developed a depressive episode, sertraline at a dose of 50 mg/day was added to the regimen. However, after a period of 4 weeks, Ms. A did not respond and had to be admitted to the hospital for suicidal thoughts. After a minimum trial of 2 weeks at each dose, the sertraline dose was increased to 100 mg/day, 200 mg/day, and then to 300 mg/day. Within 2 weeks of taking 300 mg/day, Ms. A showed a significant improvement in her sleep, appetite, energy, and concentration. After the start of sertraline treatment, 1 plasma level for carbamazepine (1000 mg/day) and 2 levels for sertraline (one at 200 mg/day and the other at 300 mg/day) were obtained. All plasma levels were obtained under our standard protocol for therapeutic drug monitoring (i.e., a stable dose maintained for at least 5 times the usual half-life of the drug and the sample obtained 10-12 hours after the last dose). Automated gas chromatographic-electron-capture assay 1 performed by the same laboratory was used for both plasma levels of sertraline, with levels below 10 ng/mL not detectable. Ms. A was using no drugs except those mentioned in the case history. Routine laboratory test results were within normal limits.Case 2. Mr. B, a 25-year-old, physically healthy white man with a long-standing diagnosis of a posttraumatic stress disorder, had been successfully treated with carbamazepine, 400 mg/day, for 13 years. When he then developed major depressive disorder, he was started on sertraline, 50 mg/day. However, Mr. B failed to respond, and, after a minimum trial of 3 weeks at each dose, sertraline was increased to 100 mg/day, 200 mg/day, and finally to 300 mg/day, which resulted in a remarkable improvement in his mood, sleep, energy, and interests. After the start of sertraline treatment, 1 plasma level each was drawn for carbamazepine (400 mg/day) and sertraline (100 mg/day). All plasma levels were obtained under our standard protocol for therapeutic drug monitoring (described above). Sertraline level was measured using automated gas chromatographic-electron-capture assay 1 using the same laboratory as in case 1, with levels below 10 ng/mL not detectable. Ms. B was using no other drugs besides those mentioned in the case history. Routine laboratory test results were within normal limits.
