Clinical trial NCT00044681: A Study of the Effectiveness and Safety of Risperidone to Augment SSRI Therapy in Patients With Treatment-resistant Depression
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Depressive Disorder
Depressive Disorder, Major
Depression
Keywords: Risperidone
depression
melancholia
depressive disorder
antipsychotic agents
Lead sponsor: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
Sponsor class: INDUSTRY
Collaborators: name: Janssen, LP
First posted: 2002-09-05
Enrollment: 258
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Change from baseline in Montgomery-Asberg Depression Rating Scale (MADRS) total score at end of treatment; time to relapse
Secondary outcomes:
measure: 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.
Other outcomes:
Locations:
Study officials:
affiliation: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
name: Johnson & Johnson Pharmaceutical Research & Development, L.L. C. Clinical Trial
role: STUDY_DIRECTOR
References: