Quetiapine Augmentation Versus Clomipramine Augmentation of SSRI for Obsessive-compulsive Disorder Patients

Overview

The objective of this trial is to compare in an open trial format the efficacy of association of clomipramine and quetiapine with SSRI after SSRI treatment failed to produce complete remission of obsessive compulsive disorder symptoms.

Full Title of Study: “Quetiapine Augmentation Versus Clomipramine Augmentation of Selective Serotonin Reuptake Inhibitors for Obsessive-compulsive Disorder Patients That do Not Respond to a SSRI Trial: a Randomized Open-trial.”

Study Type

• Study Type: Interventional
• Study Design
  • Allocation: Randomized
  • Intervention Model: Parallel Assignment
  • Primary Purpose: Treatment
  • Masking: Single (Outcomes Assessor)
• Study Primary Completion Date: December 2007

Detailed Description

The objective of this trial wis to compare in an randomized open trial format the efficacy of association of clomipramine at maximum dosage of 75mg per day and quetiapine at maximum dosage of 200mg per day with SSRI after SSRI treatment for 12 weeks failed to produce complete remission of OCD symptoms.

Interventions

• Drug: Quetiapine
  • Quetiapine once a day at maximum dosage of 200mg per day asociated to a SSRI (maximum dosage of 40mg per day for fluoxetine; 200mg per day for sertraline and 60mg per day for citalopram)
• Drug: Clomipramine
  • Clomipramine once a day at maximum dosage of 75mg per day plus SSRI (maximum dosage of 40mg per day for fluoxetine; 200mg per day for sertraline and 60mg per day for citalopram)

Arms, Groups and Cohorts

• Experimental: Quetiapine augmentation
  • Quetiapine up to 200mg/day plus SSRI at maximum tolerated or recommended dosage
• Active Comparator: Clomipramine augmentation
  • Clomipramine up to 150mg/day plus SSRI at maximum tolerated or recommended dosage

Clinical Trial Outcome Measures

Primary Measures

• YBOCS
  • Time Frame: 12 weeks
  • difference between initial and final (12 week) Yale Brown Obsessive Compulsive Scale (YBOCS)score

Secondary Measures

• CGI
  • Time Frame: 12 weeks
  • Clinical Global Impression score for improvement at week 12
• Tolerability
  • Time Frame: weeks 0,2,4,8 and 12
  • adverse events measure (emphasis in serotonergic syndrome)
• Cardiotoxicity
  • Time Frame: week 0 and 2
  • Changes in baseline (week 0) EKG regarding QT interval

Participating in This Clinical Trial

Inclusion Criteria

• primary OCD diagnosis according to DSM IV criteria – current symptoms were responsible for significant distress – previous trial of at least 12 weeks with SSRI (being at least 8 weeks at maximum tolerated dosage) failed to produce full remission of OCD symptoms Exclusion Criteria:

• presence of 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 – and current pregnancy or intention to get pregnant before the end of the treatment protocol

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: 65 Years

Are Healthy Volunteers Accepted: No

Investigator Details

• Lead Sponsor
  • University of Sao Paulo
• Collaborator
  • Conselho Nacional de Desenvolvimento Científico e Tecnológico
• Provider of Information About this Clinical Study
  • Principal Investigator: Juliana Belo Diniz, MD, PhD – University of Sao Paulo
• Overall Official(s)
  • Juliana B Diniz, MD, Principal Investigator, Department of Psychiatry University of São Paulo Medical School

References

Bloch MH, Landeros-Weisenberger A, Kelmendi B, Coric V, Bracken MB, Leckman JF. A systematic review: antipsychotic augmentation with treatment refractory obsessive-compulsive disorder. Mol Psychiatry. 2006 Jul;11(7):622-32. doi: 10.1038/sj.mp.4001823. Epub 2006 Apr 4. Erratum In: Mol Psychiatry. 2006 Aug;11(8):795.

Browne M, Horn E, Jones TT. The benefits of clomipramine-fluoxetine combination in obsessive compulsive disorder. Can J Psychiatry. 1993 May;38(4):242-3. doi: 10.1177/070674379303800402.

Denys D, de Geus F, van Megen HJ, Westenberg HG. A double-blind, randomized, placebo-controlled trial of quetiapine addition in patients with obsessive-compulsive disorder refractory to serotonin reuptake inhibitors. J Clin Psychiatry. 2004 Aug;65(8):1040-8. doi: 10.4088/jcp.v65n0803.

Fineberg NA, Sivakumaran T, Roberts A, Gale T. Adding quetiapine to SRI in treatment-resistant obsessive-compulsive disorder: a randomized controlled treatment study. Int Clin Psychopharmacol. 2005 Jul;20(4):223-6. doi: 10.1097/00004850-200507000-00005.

Pallanti S, Quercioli L, Paiva RS, Koran LM. Citalopram for treatment-resistant obsessive-compulsive disorder. Eur Psychiatry. 1999 Apr;14(2):101-6. doi: 10.1016/s0924-9338(99)80725-1.