A Long-Term Trial of the Effectiveness and Safety of Atypical Antipsychotic Agents in Augmenting SSRI-Refractory Obsessive-Compulsive Disorder

Objective: Although atypical antipsychotic agents have been found effective in the augmentation of serotonin reuptake inhibitors (SRIs) for treatment-resistant obsessive-compulsive disorder (OCD) in short-term trials, there are few data on the effectiveness and safety of these agents in clinical settings over the long term.

Method: Subjects (N = 46) who responded to selective SRIs (SSRIs) in an initial 12-week trial were continued on SSRI monotherapy plus cognitive-behavioral therapy (CBT) for 1 year. Subjects (N = 44) who failed to respond to SSRIs were randomly assigned to 1 of 3 atypicalantipsychoticsolanzapine, quetiapine, or risperidoneand were consecutively treated using SSRI+ atypical antipsychotics combined with CBT for 1 year. This study was conducted from January 2006 to November 2007 at Osaka City University Graduate School of Medicine Hospital, Japan.

Results: Augmentation with atypical antipsychotics reduced mean ± SD Yale-Brown Obsessive Compulsive Scale (YBOCS) total scores in SSRI-refractory OCD patients (at initial assessment = 29.3 ± 9.9, after 1 year = 19.3 ± 6.8). However, compared to SSRI responders (at initial assessment = 25.8±11.4, after 1 year = 13.7 ± 4.6), total YBOCS scores in those who required atypical antipsychotic augmentation were initially higher, and they remained at higher levels than those of SRI responders after 1 year of the treatments.

Conclusion: Our work does not sufficiently support the long-term effectiveness of the atypical antipsychotics in the augmentation of SSRIs for treatment-resistant OCD patients. Even though this approach seems useful for some types of OCD patients, such as those with symmetry/ordering and hoarding symptoms, these data emphasize the limitations of the current pharmacotherapeutic options in treatment-refractory OCD, and their chronic use raises a number of safety concerns.