Using Drug Augmentation to Treat Obsessive Compulsive Disorder Patients Who Did Not Respond to Previous Treatment

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 patients non-respondent to first line pharmacological treatment. The investigators will compare: fluoxetine maintenance at maximum dosage for additional 12 weeks; the association of fluoxetine with quetiapine; and the association of fluoxetine with clomipramine.

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 Investigator: University of Sao Paulo Other

Overall Clinical Trial Officials and Contacts

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

Information obtained from ClinicalTrials.gov on February 08, 2012

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