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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Obsessive Compulsive Disorder

Intervention / Treatment
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* Drug: Clomipramine (fluoxetine plus clomipramine)
* Drug: Quetiapine (fluoxetine plus quetiapine)
* Drug: Placebo (fluoxetine plus placebo)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: OCD diagnosis YBOCS score ≥ 16 (for patients with both obsessions and compulsions) or ≥ 10 (for patients with only obsessions or compulsions) Previously signed informed consent to participate in this clinical trial Exclusion Criteria: Patients with clinical or neurological diseases that may be worsen by the medications included in treatment protocol Current substance dependence or abuse Current psychotic symptoms Current suicide risk Current pregnancy or intention to get pregnant before the end of the treatment protocol

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Quetiapine (fluoxetine plus quetiapine)<br>fluoxetine up to 40mg once a day plus Quetiapine up to 200mg once a day, during 12 weeks | Drug: Quetiapine (fluoxetine plus quetiapine)<br>* Quetiapine at maximum tolerated dosage of 200mg per day plus fluoxetine at maximum dosage of 40mg per day<br>* Other names: Seroquel;|
| Active Comparator: Clomipramine (fluoxetine plus clomipramine)<br>Fluoxetine up to 40mg once a day plus clomipramine up to 75mg once a day, during 12 weeks | Drug: Clomipramine (fluoxetine plus clomipramine)<br>* Clomipramine at maximum dosage of 75mg per day plus fluoxetine at maximum dosage of 40mg per day<br>* Other names: Anafranil;|
| Placebo Comparator: Placebo (fluoxetine plus placebo)<br>Fluoxetine up to 80 mg once a day plus placebo 3 pills once a day, during 12 weeks | Drug: Placebo (fluoxetine plus placebo)<br>* Placebo plus fluoxetine at maximum dosage of 80mg per day<br>* Other names: Daforin (EMS pharmaceutics);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| YBOCS | 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 | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| QoL | Improvement of quality of life (QOL) will be assessed through SF-36 administered on weeks 0 and 12. | 12 weeks | 
| Social Adaptation | Improvement of social adaptation using the Social Adaptation Scale (SAS) (Weissman & Payket, 1974) administered on weeks 0 and 12 | 12 weeks | 
| Tolerability | Tolerability of the proposed treatments through adverse events follow-up performed each visit (emphasis in serotonergic syndrome) | weeks 0,1,2,3,4,8,12 | 
| BDI | Score obtained with Beck depression inventory (BDI) | 12 weeks | 
| BAI | Score obtained with Beck´s anxiety inventory (BAI) | 12 weeks | 
| CGI | Clinical global impression measure of improvement | 12 weeks | 
| Cardiotoxicity | Change from baseline EKG regarding QT interval | 2 weeks | 
| Plasma levels | Fluoxetine dosage and Clomipramine plasmatic dosages (when applies) | weeks 2 and 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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clomipramine, quetiapine, fluoxetine, placebo, augmentation, obsessive compulsive disorder