Effect of Add-on Citalopram to Risperidone on Negative Symptoms in Schizophrenia

Official Title: “Prospective Double-Blind Randomized Comparison Study of Improvement in Negative Symptoms With Risperidone vs Risperidone +Citalopram Combination Therapy in Schizophrenia--a Clinical Study”

Negative symptoms in schizophrenia present a challenge to the clinician owing to their poorer response to conventional treatment with antipsychotics. Negative symptoms in schizophrenia may be secondary to psychotic symptoms, depressive symptoms, drug-related side effects or lack of environmental stimulation. Alternately, they may represent core features of the illness, characterized as primary deficit symptoms. Previous studies have suggested that atypical antipsychotics may be beneficial in improving deficit symptoms of schizophrenia. This study aimed at characterizing the nature of improvement of negative symptoms in the early phase (12 weeks) of treatment with the atypical antipsychotic, risperidone. In order to account for factors contributing to improvement in secondary negative symptoms, ratings were carried out of change in positive symptoms, depressive symptoms and drug-related side effects. Further, add-on citalopram or placebo were administered in a double-blind design to study the effect of selective serotonin reuptake inhibitor (SSRI) augmentation of risperidone on negative symptoms. The investigators hypothesized that the improvement in negative symptoms during the initial phase (12 weeks) of treatment with risperidone will be largely accounted for by improvement in secondary negative symptoms, rather than of the primary deficit symptoms.

Intervention(s) in this Clinical Trial

• Drug: Risperidone
  • Risperidone: tablet; oral; 4-6 mg/day; once daily; 12 weeks
• Drug: risperidone
  • Risperidone: tablet; 4-8 mg/day; once daily; 12 weeks
• Drug: Citalopram
  • Citalopram: tablet; oral; 20 mg/day; once daily; 12 weeks
• Drug: Placebo
  • Placebo: once daily

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: Risperidone and citalopram
  • 24 patients were randomized to receive add-on citalopram (20 mg/day) in a double-blind fashion to open-label risperidone (4-8 mg/day)
• Placebo Comparator: Risperidone and placebo
  • 24 patients were randomized to receive add-on placebo in a double-blind fashion to open-label treatment with risperidone (4-8 mg/day)

Primary Measures

• Change in PANSS negative symptom score
  • Time Frame: 12 weeks
    Safety Issue?: No

Secondary Measures

• Change in PANSS total score
  • Time Frame: 12 weeks
    Safety Issue?: No

Inclusion Criteria:

• Patients fulfilling DSMIV Criteria for Schizophrenia
• The patient should be drug naïve or drug free for one month (oral antipsychotic) or three months of parental antipsychotic
• Duration from onset < 5 years
• Informed consent

Exclusion Criteria:

• Patient with any other current Axis I or Axis II comorbid disorders
• Comorbid substance abuse or dependence except nicotine or caffeine
• Presence of significant medical disorder such as epilepsy, uncontrolled hypertension and diabetes mellitus, thyroid disorder
• Patient who has not responded to adequate course of risperidone (with reference to dose and duration)
• Treatment-resistant schizophrenia defined as non-response to three different antipsychotics belonging to at least two different classes, one of which is an atypical agent and one of which is a depot neuroleptic
• Patient who has received ECT in past 3 months

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 17 Years

Maximum Age for this Clinical Trial: 50 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Investigator: National Institute of Mental Health and Neuro Sciences, India Other

Overall Clinical Trial Officials and Contacts

John P John, M.D. Principal Investigator National Institute of Mental Health and Neurosciences, Bangalore, INDIA  

Information obtained from ClinicalTrials.gov on February 09, 2012

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00893256

Study ID Number: NFRPA/006/2004

ClinicalTrials.gov Identifier: NCT00893256

Health Authority: India: Institutional Review Board