OCDDRUG: Effectiveness and Safety of Atypical Antipsychotic Agents in Augmenting SSRI-Refractory Obsessive-Compulsive Disorder

Sponsor

Osaka City University (Other)

Overall Status

Completed

CT.gov ID

NCT00854919

Collaborator

(none)

Location

Arms

Duration (Months)

Study Details

Study Description

Brief Summary

Objective: Although atypical antipsychotic drugs (AAPDs) have been found effective in the augmentation of serotonin reuptake inhibitors (SRIs) for treatment-resistant obsessive-compulsive disorder (OCD) in short terms trials, there are few data on the effectiveness and safety of these agents in clinical settings over the long term.

Method: Subjects (n=46) who responded to selective SRIs (SSRIs) in an initial 12-week trial were continued on SRI-monotherapy plus cognitive-behavioral therapy (CBT) for one year. Subjects (n=44) who failed to respond to SSRIs were randomly assigned to one of 3 AAPDs such as risperidone and were consecutively treated using SSRI+AAPD combined with CBT for a year.

Condition or Disease	Intervention/Treatment	Phase
SSRI-Refractory Obsessive-Compulsive Disorder	Drug: atypical antipsychotic drug Behavioral: exposure response prevention	Phase 4

Detailed Description

More recently, second-generation atypical antipsychotic drugs (AAPD) that modulate both 5-HT and DA function, such as risperidone (RIS), olanzapine (OLZ) and quetiapine (QET), have been found effective in the augmentation of SSRIs for treatment-resistant OCD.

Nevertheless, the AAPDs have been associated with common and serious adverse effects, such as body weight (BW) gain and metabolic dysregulation. Metabolic dysregulation includes glucoregulatory dysfunction and dyslipidemia. Indeed, studies of some AAPD in SSRI-refractory OCD patients have similarly reported significant BW gain. AAPD-induced BW gain may influence patients' adherence to medication and places them at risk for a broad range of medical problems.

Most work on AAPDs in treatment-refractory OCD has been conducted in the form of short-term efficacy studies. There have been fewer studies of the effectiveness, safety, and tolerability of these agents in the context of a clinic where CBT is also provided, and where treatment is continued for a significant period of time. In the current effectiveness study, we sought to examine the response of SSRI-refractory patients to augmentation with AAPDs, comparing adverse events in such compared to a control group of SSRI responders.

Study Design

Study Type:

Interventional

Official Title:

An Long Term Trial on Effectiveness and Safety of Atypical Antipsychotic Agents in Augmenting SSRI-Refractory Obsessive-Compulsive Disorder

Study Start Date :

Jan 1, 2006

Actual Primary Completion Date :

Dec 1, 2007

Actual Study Completion Date :

Dec 1, 2007

Arms and Interventions

Arm	Intervention/Treatment
Experimental: CBT All subjects received cognitive-behavioral therapy (CBT) during the study period.	Behavioral: exposure response prevention After at least 12 weeks from treatment initiation, cognitive-behavioral therapy (CBT) using exposure and response prevention was added with psychoeducational interventions and behavioral analysis.
Experimental: 1 Drug; Paroxetine (30-50mg/D)or Fluvoxamine (150-250mg/D), 1-year administration	Drug: atypical antipsychotic drug For SSRI-refractory group, either atypical antipsychotic such as mean doses of RIS (3.1±1.9mg/day), of OLZ (5.1±3.2mg/day), and of QET (60.0±37.3mg/day) was added on ongoing SSRI(Paroxetine, Fluvoxamine). Behavioral: exposure response prevention After at least 12 weeks from treatment initiation, cognitive-behavioral therapy (CBT) using exposure and response prevention was added with psychoeducational interventions and behavioral analysis.
Active Comparator: 2 Either risperidone (1-5mg/D), olanzapine (1-5mg/D) or quetiapine (25-100mg/D) was added to ongoing SSRI, the combination trial was continued at least for half a year.	Drug: atypical antipsychotic drug For SSRI-refractory group, either atypical antipsychotic such as mean doses of RIS (3.1±1.9mg/day), of OLZ (5.1±3.2mg/day), and of QET (60.0±37.3mg/day) was added on ongoing SSRI(Paroxetine, Fluvoxamine). Behavioral: exposure response prevention After at least 12 weeks from treatment initiation, cognitive-behavioral therapy (CBT) using exposure and response prevention was added with psychoeducational interventions and behavioral analysis.

Arm

Intervention/Treatment

Experimental: CBT

All subjects received cognitive-behavioral therapy (CBT) during the study period.

Behavioral: exposure response prevention

After at least 12 weeks from treatment initiation, cognitive-behavioral therapy (CBT) using exposure and response prevention was added with psychoeducational interventions and behavioral analysis.

Experimental: 1

Drug; Paroxetine (30-50mg/D)or Fluvoxamine (150-250mg/D), 1-year administration

Drug: atypical antipsychotic drug

For SSRI-refractory group, either atypical antipsychotic such as mean doses of RIS (3.1±1.9mg/day), of OLZ (5.1±3.2mg/day), and of QET (60.0±37.3mg/day) was added on ongoing SSRI(Paroxetine, Fluvoxamine).

Behavioral: exposure response prevention

After at least 12 weeks from treatment initiation, cognitive-behavioral therapy (CBT) using exposure and response prevention was added with psychoeducational interventions and behavioral analysis.

Active Comparator: 2

Either risperidone (1-5mg/D), olanzapine (1-5mg/D) or quetiapine (25-100mg/D) was added to ongoing SSRI, the combination trial was continued at least for half a year.

Drug: atypical antipsychotic drug

Behavioral: exposure response prevention

After at least 12 weeks from treatment initiation, cognitive-behavioral therapy (CBT) using exposure and response prevention was added with psychoeducational interventions and behavioral analysis.

Outcome Measures

Primary Outcome Measures

Yale-Brown Obsessive-Compulsive Scale [1 year]

Secondary Outcome Measures

yale-Brown Obsessive-Compulsive Scale [1 year]
BMI, TG, T-CHO, FBS [1 year]

Eligibility Criteria

Criteria

Ages Eligible for Study:

20 Years to 50 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Male or female, 18 years of age or over
Patients were diagnosed as having obsessive-compulsive disorder by the Structured Clinical Interview for DSM-IV Patient version (SCID-P)
They received standardized treatment for at least 1 year at the OCD clinic in our university hospital.
Each subject gave written informed consent to take part after receiving a complete description of this study.
All subjects were free of medical illness based on results of physical examination and screening tests of blood and urine, and no subjects received any lipid lowering or hypoglycemic agent during the 1-year study period.