SSRI-TCA Combination in the Treatment of Resistant Depression

Abstract

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.

Misdiagnosis of antidepressant discontinuation symptoms

“…I agree with the former statement but not with the latter. There is some evidence that a selective serotonin reuptake inhibitor (SSRI) and a tricyclic antidepressant (TCA) combination may be useful in the treatment of resistant depression (2, 3). Therefore, also in the case of Haddad and Qureshi (1), if the second antidepressant (dothiepin) had been added to the first antidepressant (paroxetine), the patient's depression might have improved more rapidly without the patient's experiencing paroxetine withdrawal symptoms.…”