A Study of the Effectiveness and Safety of Risperidone to Augment SSRI Therapy in Patients With Treatment-resistant Depression

Depression Clinical Trial

Official title:

A Study to Evaluate the Efficacy, Safety and Maintenance Effect of Risperidone Augmentation of SSRI Monotherapy in Young and Older Adult Patients With Unipolar Treatment-Resistant Depression

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00044681
• Other study ID #: CR002143
• Status: Completed
• Phase: Phase 3
• First received: September 3, 2002
• Last updated: May 17, 2011
• Start date: October 2002
• Est. completion date: March 2004

Study information

• Verified date: November 2010
• Source: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to evaluate the effectiveness and safety of risperidone to augment SSRI therapy in patients with treatment-resistant depression and to demonstrate the long-term maintenance effect of risperidone as augmentation therapy compared with placebo augmentation in these patients.

Description:

Treatment strategies for treatment-resistant depression (TRD) involve either switching to another antidepressant, augmenting the first-line treatment with various pharmacologic agents, or switching to a different medication in combination with another agent. This study includes 2 phases: an open-label treatment phase and a double-blind maintenance phase, during which neither the patient nor the physician knows whether risperidone or placebo is administered. The open-label phase has an initial period of 6 weeks during which patients with TRD receive only citalopram, a selective serotonin reuptake inhibitor (SSRI). Risperidone is then added to the treatment regimen for 4 weeks to evaluate its short-term effect in augmenting the therapy. The double-blind phase last for 6 months and evaluates the relapse prevention of continued risperidone augmentation therapy compared with placebo augmentation of the SSRI. Targeted daily doses of citalopram and risperidone are adjusted for younger adults (18 to 54 years of age) and older adults (55 to 85 years of age). Assessments of effectiveness include the Montgomery-Asberg Depression Rating Scale (MADRS); Hamilton Rating Scale of Depression (HAM-D); Clinical Global Impression of Severity (CGI-S); response rate, determined by the proportion of patients showing >=50% improvement on MADRS total score; and relapse, evaluated by changes in CGI or HAM-D scores. Safety evaluations include the incidence of adverse events throughout the study, vital signs (pulse and blood pressure) and weight, and clinical laboratory tests (hematology, biochemistry, urinalysis) at specified intervals. The study hypothesis is that risperidone augmentation of SSRI therapy will show significant improvement in symptoms of depression compared with SSRI monotherapy and that risperidone augmentation will show better time-to-relapse than placebo augmentation in patients with TRD. Once daily, oral tablets of risperidone (0.25 milligram[mg], 0.5mg, 1.0mg, and 2.0mg), citalopram (20mg and 40mg) or placebo. Risperidone for 30 weeks; 0.25-2.0mg for younger adults, 0.25-1.0mg for older adults. Citalopram for 36 weeks; 20-60 mg for younger adults; 20-40 mg for older adults.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 258
• Est. completion date: March 2004
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 85 Years

Eligibility

Inclusion Criteria:

• Meet criteria of Diagnostic and Statistical Manual of Mental Diseases, 4th edition (DSM-IV), for Major Depressive Disorder

• history of resistance to therapy with antidepressant medication

• score on the Hamilton Rating Scale of Depression (HAM-D) of >=20 at start of study.

Exclusion Criteria:

• Meet DSM-IV criteria for Axis I disorder (except anxiety disorders) or borderline personality disorder

• substance dependence, including drugs of abuse and alcohol

• history of schizophrenia, bipolar disorder, or manic episode

• meet DSM-IV criteria for delirium, dementia, amnesic or other cognitive disorder supported by Mini Mental Status Examination (MMSE)

• pregnant or nursing females, or those lacking adequate contraception.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double-Blind, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Depression
• Depressive Disorder
• Depressive Disorder, Major
• Depressive Disorder, Treatment-Resistant
• Disease

Intervention

Drug:
• risperidone

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Johnson & Johnson Pharmaceutical Research & Development, L.L.C.	Janssen, LP

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change from baseline in Montgomery-Asberg Depression Rating Scale (MADRS) total score at end of treatment; time to relapse
Secondary	Response rate, determined from >=50% improvement from baseline at MADRS total score; change from baseline in Hamilton Rating Scale of Depression (HAM-D) and Clinical Global Impression (CGI) scale; incidence of adverse events throughout study.

External Links

•   A Study to Evaluate the Efficacy, Safety and Maintenance Effect of Risperidone Augmentation of SSRI Monotherapy in Young and Older Adult Patients with Unipolar Treatment-Resistant Depression