Addition of risperidone to sertraline improves sertraline-resistant refractory depression without influencing plasma concentrations of sertraline and desmethylsertraline.

In the present study, we examined the efficacy of risperidone addition on sertraline-resistant depressed patients and the effects of risperidone on the metabolism of sertraline. Ten patients (M/F: 4/6, age: 54 +/- 10 years) met the DSM-IV criteria for major depressive disorder enrolled the study. Hamilton Dating Scale for Depression (HAM-D) scores (mean +/- SD) in all 10 patients significantly decreased from 19 +/- 4 (before risperidone addition) to 11 +/- 3 (4 weeks after risperidone addition). Plasma levels of sertraline and desmethylsertraline did not change after risperidone addition. Serum BDNF levels in responders to risperidone addition were changed from 8.1 +/- 2.7 ng/ml (before risperidone addition) to 11.5 +/- 0.9 ng/ml (4 weeks after risperidone addition); in contrast, those in nonresponders changed from 7.8 +/- 2.2 ng/ml (before risperidone addition) to 7.9 +/- 2.4 ng/ml (4 weeks after risperidone addition). These results suggest that the addition of risperidone to sertraline is effective and well tolerated for sertraline-resistant depressive patients, which is accompanied with the increase in serum BDNF levels in responders to the risperidone addition, and the addition of risperidone to sertraline does not seem to influence sertraline metabolism.