Effect of Add-on Citalopram to Risperidone on Negative Symptoms in Schizophrenia (RIS-CIT-SCH)

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.

Study Overview

• Status: Completed
• Conditions: Schizophrenia; Negative Symptoms
• Intervention / Treatment: Drug: Risperidone; Drug: Citalopram; Drug: risperidone; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 48
• Phase: Phase 4

Contacts and Locations

Study Locations

• India
  • Karnataka
    • Bangalore, Karnataka, India, 560 029
      • National Institute of Mental Health and Neurosciences (NIMHANS)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 17 years to 50 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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)	Drug: Risperidone; Risperidone: tablet; oral; 4-6 mg/day; once daily; 12 weeks; Other Names: Respidon; Drug: Citalopram; Citalopram: tablet; oral; 20 mg/day; once daily; 12 weeks; Other Names: Citopam
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)	Drug: risperidone; Risperidone: tablet; 4-8 mg/day; once daily; 12 weeks; Other Names: Respidon; Drug: Placebo; Placebo: once daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change in PANSS negative symptom score	12 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Change in PANSS total score	12 weeks

Collaborators and Investigators

• Sponsor: National Institute of Mental Health and Neuro Sciences, India
• Investigators: Principal Investigator: John P John, M.D., National Institute of Mental Health and Neurosciences, Bangalore, INDIA

Study record dates

Study Major Dates

• Study Start: December 1, 2004
• Primary Completion (Actual): September 1, 2007
• Study Completion (Actual): September 1, 2007

Study Registration Dates

• First Submitted: May 4, 2009
• First Submitted That Met QC Criteria: May 4, 2009
• First Posted (Estimate): May 5, 2009

Study Record Updates

• Last Update Posted (Estimate): May 5, 2009
• Last Update Submitted That Met QC Criteria: May 4, 2009
• Last Verified: May 1, 2009

More Information

Terms related to this study

• Keywords: schizophrenia; risperidone; citalopram; secondary negative symptoms
• Additional Relevant MeSH Terms: Mental Disorders; Schizophrenia Spectrum and Other Psychotic Disorders; Schizophrenia; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Antipsychotic Agents; Tranquilizing Agents; Psychotropic Drugs; Serotonin Uptake Inhibitors; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Serotonin Agents; Antidepressive Agents; Dopamine Agents; Serotonin Antagonists; Dopamine Antagonists; Antidepressive Agents, Second-Generation; Citalopram; Risperidone
• Other Study ID Numbers: NFRPA/006/2004