A Study of the Effectiveness and Safety of Risperidone to Augment SSRI Therapy in Patients With Treatment-resistant Depression
Condition: Depressive Disorder; Depressive Disorder, Major; Depression
MeSH terms: Depression; Depressive Disorder; Depressive Disorder, Treatment-Resistant; Depressive Disorder, Major
Study type: Interventional
Phase: Phase 3

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.
    

Intervention name(s): risperidone
Intervention type(s): Drug
Intervention MeSH terms: Risperidone
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double
Primary purpose: Treatment
Keywords: Risperidone; depression; melancholia; depressive disorder; antipsychotic agents