Double Blinded, Placebo-Controlled Trial of Paliperidone Addition in SRI-Resistant Obsessive-Compulsive Disorder

Obsessive-Compulsive Disorder Clinical Trial

Official title: Double Blinded, Placebo-Controlled Trial of Paliperidone Addition in SRI-Resistant Obsessive-Compulsive Disorder

Status Completed

Clinical Trial Summary

Obsessive-compulsive disorder (OCD) is a common, chronic, and oftentimes disabling disorder. The only established treatments for OCD are a specific form of Cognitive Behavioral Therapy (CBT) and the Serotonin Reuptake Inhibitor medications (SRIs). Few patients with OCD experience complete symptom resolution with either modality and even after two consecutive SRI trials, as many as 30%-40% of patients fail to derive a satisfactory response. Pharmacological options for these SRI-resistant cases include switching to a different antidepressant, increasing the dose of SRI, or augmentation with another agent.

Previous studies showed that approximately 33-50% of OCD patients who have not had an adequate response to SRI medication had a positive response when an atypical antipsychotic medication was added. However, the problematic acute and long-term side effects of these medications are of concern and, at times, limit their use. Paliperidone has a number of advantages over these medications including fewer drug interactions and better tolerability. Thus, this study is designed to determine whether paliperidone augmentation of an existing medication is effective relative to taking a placebo and your existing medication.

Clinical Trial Description

Obsessive-compulsive disorder (OCD) is a common, chronic, and oftentimes disabling disorder. The only established first-line treatments for OCD are a specific form of Cognitive Behavioral Therapy (CBT) and the Serotonin Reuptake Inhibitors (SRIs). Few patients with OCD experience complete symptom resolution with either modality. Even after two consecutive adequate SRI trials, as many as 30%-40% of patients fail to derive a satisfactory response. Pharmacological options for these SRI-resistant cases include switching to a different antidepressant, increasing the dose of SRI, or augmentation with another agent.

Among the pharmacological augmentation strategies, adjunctive antipsychotic medications enjoy the most empirical support as well as wide-scale use in clinical practice. Utilizing IMS Health's National Disease and Therapeutic Index (NDTI) for 12 months ending in November 2004, 4.2% of antipsychotic medication use is for anxiety and 1.3% specifically for OCD. Conversely, for OCD patients, antipsychotic medications account for 8.6% of drug use (IMS Health NDTI MAT, 2004). Among pediatric patients, prescriptions of antipsychotics increased from 8.6 out of 1,000 U.S. children in 1995-1996 to 39.4 out of 1,000 children in 2001-2002 (Cooper et al., 2006). Similarly, Medco, a private insurance company, noted that the rate of children 19 years and under covered by private insurance with at least one atypical prescription jumped 80% from 2001 to 2005 — from 3.6 per 1,000 to 6.5 per 1,000 (USA Today, extracted 5/2/2006). These rates parallel our own research, in which approximately 35% of adult patients on psychotropics were taking an antipsychotic in addition to their SRI. Thus, clearly there is a large sample of OCD patients that are being prescribed atypical antipsychotics to augment other treatments.

Previous studies showed that approximately 33-50% of OCD patients who have not had an adequate response to SRI medication had a positive response when an atypical antipsychotic medication was added (Bloch et al., 2006). Risperidone has been the most studied agent and has the most consistently positive findings (e.g., McDougle et al., 2000). However, the problematic acute and long-term side effects of risperidone (and other atypicals) are of concern and, at times, limit their use. Paliperidone, a metabolite of risperidone that utilizes OROS osmotic drug-release technology, has a number of advantages over risperidone including a lack of drug x drug interactions and a predictable pharmacokinetic profile that is associated with better tolerability. Thus, paliperidone has the potential to be a safer alternative for augmentation in OCD patients pending supporting efficacy data. Given the need to examine the efficacy of paliperidone, this protocol is designed to determine whether paliperidone augmentation of an SRI is effective relative to a placebo-control, and safe/tolerable in patients with OCD who have not adequately responded to past adequate SRI treatment. ;

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Compulsive Behavior
• Obsessive-Compulsive Disorder

• NCT number: NCT00632229
• Study type: Interventional
• Source: University of South Florida
• Status: Completed
• Phase: Phase 2
• Start date: October 2007
• Completion date: September 2013