• Improvement of quality of life (QOL) will be assessed through SF-36 administered on weeks 0 and 12; [ Time Frame: 12 weeks ] [ Designated as 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 ] [ Designated as 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 ] [ Designated as safety issue: Yes ]
• Score obtained with Beck depression inventory (BDI) [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
• Score obtained with Beck´s anxiety inventory (BAI) [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
• Clinical global impression measure of improvement [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
• Change from baseline EKG regarding QT interval [ Time Frame: 2 weeks ] [ Designated as safety issue: Yes ]
• Fluoxetine dosage and Clomipramine dosage (when applies) [ Time Frame: weeks 2 and 12 ] [ Designated as safety issue: Yes ]

• Improvement of quality of life (QOL) will be assessed through SF-36 administered on weeks 0 and 12;
• Improvement of social adaptation using the Social Adaptation Scale (SAS) (Weissman & Payket, 1974) administered on weeks 0 and 12;
• Tolerability of the proposed treatments through adverse events follow-up performed each visit (weeks 0,2,4,8,12).

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.

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.

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

  • Prozac
  • Daforin (EMS pharmaceutics)

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

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

• Fundação de Amparo à Pesquisa do Estado de São Paulo
• Conselho Nacional de Desenvolvimento Científico e Tecnológico
• Novartis