P.4.d.002 Effect of ziprasidone augmentation of serotonin reuptake inhibitors in treatment-resistant obsessive–compulsive disorder

Introduction: Obsessive–compulsive disorder (OCD) is a chronic and often disabling disorder that affects 2% to 3% of the general population with a major impact on several domains, including social functioning, employment, marriage and family relationships, and socioeconomic status. Serotonin reuptake inhibitors (SRIs) are considered firstline pharmacological treatments for patients with Obsessive– compulsive disorder (OCD); however, SRIs have found to be effective as monotherapy in only 40% to 60% of OCD patients, with some patients showing a substantial degree of residual symptoms [1]. Within this context, treatment options for patients who incompletely respond to SRIs include switching, augmentation, and novel agent strategies. One of the most well-documented augmentation strategies consists in the addition of antipsychotic drugs to the ongoing SRI treatment; antipsychotic augmentation in treatment-resistant OCD is yet well supported by meta-analysis [2] and by recent reviews [3], which tend to confirm the efficacy of this treatment strategy. At the best of our knowledge, few studies have evaluated the efficacy of ziprasidone adjunctive therapy in treatment-resistant OCD; no published open-label or controlled trials were identified in the literature. The present study explored the efficacy on clinical symptoms and cognitive functioning of ziprasidone add-on pharmacotherapy in a sample of patients with treatment-resistant OCD receiving SRIs. Methods: 10 OCD patients (8 males/2 females), who demonstrated persistent obsessive–compulsive symptoms despite an adequate trial with an SRI for at least 12 weeks, received ziprasidone 80 mg/day for a 12 week period. Dosages of SRIs had been stable for at least 2 months before the study and were left unchanged throughout the study. Clinical symptomatology was assessed using the Yale-Brown Obsessive Compulsive Scale (Y-BOCS), and the Hamilton Rating Scale for Depression (HDRS). All subjects underwent a neuropsychological assessment of cognitive functions (Wisconsin Card Sorting Test − WCST, Stroop Color-Word Test, Digit-Span Task, Trail Making Test). Continuous data were expressed as mean±SD and the within-group differences in efficacy ratings between baseline and final test were analysed by the Wilcoxon rank sum test. A significance value of p<0.05 was chosen. Results: No significant changes was observed in clinical sympotomatology and in cognitive functions. Only 2 patients (20%) met response criteria of 25% improvement or greater in Y-BOCS total score versus baseline. Conclusions: Based on our findings, adjunctive ziprasidone treatment appeared to be scarcely effective for improving clinical symptomatology and cognitive functions in patients with OCD who have had an incomplete response to SRIs. These results should be interpreted with caution due to the presence of a number of limitations, such as the small sample size, the open design and the low dose of ziprasidone, that limit the extent to which our findings may be extended to OCD population; further studies on broader samples are necessary to better define the potential effect of this approach. References [1] Pallanti, S., Quercioli, L., 2006. Treatment-refractory obsessive– compulsive disorder: methodological issues, operational definitions and therapeutic lines. Prog Neuropsychopharmacol Biol Psychiatry 30, 400–412. [2] Skapinakis, P., Papatheodorou, T., Mavreas, V., 2007. Antipsychotic augmentation of serotonergic antidepressants in treatment-resistant obsessive–compulsive disorder: a meta-analysis of the randomized controlled trials. Eur Neuropsychopharmacol. 17, 79−93. [3] Gao, K., Muzina, D., Gajwani, P., et al., 2006. Efficacy of typical and atypical antipsychotics for primary and comorbid anxiety symptoms or disorders: a review. J Clin Psychiatry. 67, 1327–1340