Double Blinded, Placebo-Controlled Trial of Paliperidone Addition in SRI-Resistant Obsessive-Compulsive Disorder
Condition: Obsessive-Compulsive Disorder
MeSH terms: Compulsive Personality Disorder; Obsessive-Compulsive Disorder
Study type: Interventional
Phase: Phase 2

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.
    

Detailed 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.
    

Intervention name(s): Paliperidone; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): Paliperidone medication taken daily ranging from 3-9mg/day depending on tolerability and efficacy.; Pill placebo taken daily ranging from 3-9mg/day depending on tolerability and efficacy.
Other intervention name(s): Invega
Intervention MeSH terms: Paliperidone Palmitate
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Obsessive-Compulsive Disorder; Adults; Medication; Treatment