An Open Pilot Study Combining Risperidone and a Selective Serotonin Reuptake Inhibitor as Initial Antidepressant Therapy

Background: Atypical antipsychotics such as risperidone or olanzapine have been reported to be effective when added to a selective serotonin reuptake inhibitor (SSRI) in cases of depression in which treatment with an SSRI alone is not effective. It is possible that the combination of an SSRI and an atypical antipsychotic may be efficacious as an initial treatment for major depression.

Method: Thirty-six subjects who fulfilled DSM-IV diagnostic criteria for major depressive disorder were given fluvoxamine, 50 or 75 mg/day, with risperidone, 0.5 or 1 mg/day, at the start of treatment. The dose of fluvoxamine was increased to 100 or 150 mg/day on the fourth day of the treatment and maintained thereafter. Hamilton Rating Scale for Depression (HAM-D) scores were obtained at baseline and every week for 6 weeks. Remission and response were defined, respectively, as >=75% and 50%-74% reduction from baseline in HAM-D score.

Results: Of 30 subjects who completed the 6-week study, 23 (76%) achieved remission, 5 (17%) achieved response, and 2 (7%) were nonresponsive. Of the 6 patients who did not complete the study, 3 showed remission, 1 showed response, and 2 showed minimal or no response by the time of dropout. The reported adverse effects were mild, and none of the 36 subjects enrolled in the study manifested or reported extrapyramidal symptoms, nausea, or vomiting.

Conclusion: The results suggest that the combination of risperidone and fluvoxamine from the beginning of antidepressant therapy enhances the therapeutic response rate in depression.