Low-dose risperidone augmentation of fluvoxamine treatment in obsessive-compulsive disorder: a double-blind, placebo-controlled study.

According to previous data, the addition of risperidone in obsessive-compulsive patients refractory to serotonin reuptake inhibitors (SRIs) is shown to be a safe and effective treatment strategy. The aims of our study were to evaluate the efficacy of risperidone addition, in comparison to placebo, in fluvoxamine-refractory obsessive-compulsive patients and to investigate whether risperidone could boost the efficacy of fluvoxamine in fluvoxamine-responder patients. Subjects were 45 obsessive-compulsive inpatients, consecutively recruited at the Department of Neurosciences at the San Raffaele Hospital, Milan. Thirty-nine patients completed the study. All patients received 12 weeks of a standardized open-label fluvoxamine monotherapy and then continued for 6 weeks with placebo or risperidone in a double-blind design. Results showed a significant effect of risperidone addition, at the end of the double-blind phase (18th week), only for fluvoxamine-refractory patients. Five patients on risperidone (50%) and two (20%) on placebo became responders, with a Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) decrease > or =35%. Risperidone was generally well tolerated, except for a mild transient sedation and a mild increase in appetite. This preliminary study suggests that even very low (0.5 mg) risperidone doses are effective in OC patients who were nonresponders to a standardized treatment with fluvoxamine.

Exploratory factor analysis of obsessive-compulsive patients and association with 5-HTTLPR polymorphism.

The determination of a genetic basis for obsessive-compulsive disorder (OCD) depends on how phenotypic boundaries are defined. Although a hypothesis for serotonin dysfunction in OCD has been advanced, no genes specifically responsible for serotonin regulation have as yet been definitively related to the etiology of OCD. The phenotypic variability of OCD could be at the basis of the failure of molecular biology investigations to find any genes involved in the liability to the disorder. Obsessive and compulsive contents can aggregate in OCD patients differently; multifactorial description may therefore be able to account for OCD phenotypic variance. Using principal component analysis, we derived five factors from 13 main contents of the Yale-Brown Obsessive-Compulsive Scale (YBOCS), and considered them as quantitative phenotypes to evaluate their possible association with an insertion/deletion polymorphism in the promoter region of the serotonin transporter gene (5-HTTLPR). A trend toward positive association between the fifth factor, including counting and repeating rituals, and 5-HTTLPR was found. However, only considering the subgroup of patients with tic codiagnosis, we found a significantly higher score for the fifth factor for patients with L/L genotype with respect to L/S and S/S genotypes.