Official Title: “Pharmacological Augmentation Strategies for Obsessive Compulsive Disorder Patients Non-respondent to First Line Medication Treatment: a Double Blind Placebo Controlled Study”

This will be a controlled, randomized, double-blind and double-dummy study on the treatment augmentation strategy for obsessive compulsive disorder (OCD). The investigators will compare the association of an SSRI (fluoxetine) with quetiapine, Selective serotonin reuptake inhibitors (SSRI) with clomipramine and SSRI with placebo for 12 weeks.

Study Type: Interventional

Study Design: Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment, Safety/Efficacy Study

Study Primary Completion Date: June 2010

Arm 1: SSRI (Fluoxetine 40mg* once a day) + Clomipramine 75mg* once a day.

Arm 2: SSRI (Fluoxetine 40mg* once a day) + Quetiapine 200mg* once a day.

Arm 3: SSRI (Fluoxetine 80mg* once a day) + Placebo once a day. *or maximum tolerated dose

We hypothesize that quetiapine and clomipramine will be effective augmentation strategies for resistant OCD patients in comparison to placebo.

Intervention(s) in this Clinical Trial

• Drug: clomipramine and fluoxetine
  • Clomipramine at maximum dosage of 75mg per day plus fluoxetine at maximum dosage of 40mg per day
• Drug: quetiapine and fluoxetine
  • Quetiapine at maximum tolerated dosage of 200mg per day plus fluoxetine at maximum dosage of 40mg per day
• Drug: placebo and fluoxetine
  • Placebo plus fluoxetine at maximum dosage of 80mg per day

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: Quetiapine augmentation
  • fluoxetine up to 40mg once a day plus Quetiapine up to 200mg once a day, during 12 weeks
• Experimental: Clomipramine augmentation
  • Fluoxetine up to 40mg once a day plus clomipramine up to 75mg once a day, during 12 weeks
• Placebo Comparator: Placebo
  • Fluoxetine up to 80 mg once a day plus placebo 3 pills once a day, during 12 weeks

Primary Measures

• Rates of improvement after 12 weeks of treatment based on the difference of initial and final Yale Brown Obsessive Compulsive Scale (YBOCS) scores for obsessions and compulsions
  • Time Frame: 12 weeks
    Safety Issue?: No

Secondary Measures

• Improvement of quality of life (QOL) will be assessed through SF-36 administered on weeks 0 and 12;
  • Time Frame: 12 weeks
    Safety Issue?: No
• Improvement of social adaptation using the Social Adaptation Scale (SAS) (Weissman & Payket, 1974) administered on weeks 0 and 12
  • Time Frame: 12 weeks
    Safety Issue?: No
• Tolerability of the proposed treatments through adverse events follow-up performed each visit (emphasis in serotonergic syndrome)
  • Time Frame: weeks 0,1,2,3,4,8,12
    Safety Issue?: Yes
• Score obtained with Beck depression inventory (BDI)
  • Time Frame: 12 weeks
    Safety Issue?: No
• Score obtained with Beck´s anxiety inventory (BAI)
  • Time Frame: 12 weeks
    Safety Issue?: No
• Clinical global impression measure of improvement
  • Time Frame: 12 weeks
    Safety Issue?: No
• Change from baseline EKG regarding QT interval
  • Time Frame: 2 weeks
    Safety Issue?: Yes
• Fluoxetine dosage and Clomipramine dosage (when applies)
  • Time Frame: weeks 2 and 12
    Safety Issue?: Yes

Inclusion Criteria:

• 1. OCD diagnosis
• 2. YBOCS score ≥ 16 (for patients with both obsessions and compulsions) or ≥ 10 (for patients with only obsessions or compulsions)
• 3. Previously signed informed consent to participate in this clinical trial

Exclusion Criteria:

• 1. Patients with clinical or neurological diseases that may be worsen by the medications included in treatment protocol
• 2. Current substance dependence or abuse
• 3. Current psychotic symptoms
• 4. Current suicide risk
• 5. Current pregnancy or intention to get pregnant before the end of the treatment protocol

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: 65 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: University of Sao Paulo

Overall Clinical Trial Officials and Contacts

Juliana B Diniz, MD Principal Investigator University of Sao Paulo Medical School  

Overall Contact: Marines Joaquim, Nurse 5511 30696972 majoaquim.protoc@gmail.com

Information obtained from ClinicalTrials.gov on February 08, 2010

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00466609

Study ID Number: 05/55628-8

ClinicalTrials.gov Identifier: NCT00466609

Health Authority: Brazil: National Committee of Ethics in Research

Main research group involved in this study

Institutional site of main sponsor