Risperidone and Zotepine in the Treatment of Delirium

Delirium is an organic psychiatric syndrome characterized by fluctuating consciousness and impairment in perception, cognition and behavior. In hospitalized elderly, the prevalence of delirium ranges from 10% to 40%. If untreated, delirium is associated with significant morbidity and mortality. Treatment of delirium consists of identifying and managing underlying medical abnormalities and the associated psychiatric symptoms. Conventional antipsychotics have been the mainstay of treatment of agitation and psychosis associated with delirium; but their use is limited in terms of EPS side effects. Second-generation antipsychotic agents have been reported to have a lower incidence of extrapyramidal side effects and tardive dyskinesia which has resulted in their increased use in the treatment of delirious patients. However, there is still no consensus regarding standard pharmacologic treatment of this syndrome that takes use of second-generation antipsychotic agents into account.

Risperidone and zotepine have a lower incidence of EPS and are effective in treating disturbing psychotic behaviors. We hope to compare the efficacy and safety of risperidone and zotepine in the treatment of delirium and the correlation between the severity of delirium with autonomic dysfunction.

Study Overview

• Status: Terminated
• Conditions: Delirium
• Intervention / Treatment: Drug: Risperidone and Zotepine for delirium

Detailed Description

Qualified inpatients will be enrolled and randomly given a flexible-dose regimen of Risperidone or Zotepine. Autonomic dysfunction is checked using analysis of heart rate variability before any active drug given. The initial starting dose of each drug is 1mg(risperidone) or 50 mg(zotepine) once a day. The dosage was increased depending on the status of delirium during the first 7 days and will be adjusted until patients are maximally stabilized or until intolerable adverse events necessitated cessation. Risperidone or zotepine will be tapered off in 10 days when patients are considered stable. No concomitant psychotropic medications will be used during the study except for lorazepam, which are given for severe agitation or insomnia . Patients are assessed by another rater blinded to active drug at the time of enrollment, the subsequent 12, 24,and then assessed daily until discharge. The study period is estimated to be around 12 months upon the designed number of subjects are reached.

• Study Type: Interventional
• Enrollment (Actual): 5
• Phase: Phase 4

Contacts and Locations

Study Locations

• Taiwan
  • Changhua, Taiwan, 500
    • Changhua Christian Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 81 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients may be included in the study if they meet all of the following criteria:DSM-IV-TR delirium (293.0 delirium due to general medical condition, 290.3 dementia with delirium 290.41, arteriosclerotic dementia with delirium 780.09delirium NOS. 292.8 substance-induced delirium( excluding alcohol and BZD)
• Age 18 to 85 year-old inpatients; either sex
• Patients are able to take Risperidone or Zotepine orally

Exclusion Criteria:

• Alcohol-induced delirium; delirium caused by seizures; Sedative, hypnotic or anxiolytic withdrawal delirium
• Patients with schizophrenia or bipolar disorder or being treated with antipsychotics
• Patients are mandatory to take parenteral treatments
• Patients are known to be allergic to Risperidone or Zotepine
• Women with pregnancy or during lactation.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1; zotepine , start from 50mg/day then titrate according to individual case	Drug: Risperidone and Zotepine for delirium; try risperidone or zotepine in the treatment of delirium; Other Names: risperidone( Risperdal), zotepine( Lodopine)
Active Comparator: 2; Risperidone, start from 1mg/day	Drug: Risperidone and Zotepine for delirium; try risperidone or zotepine in the treatment of delirium; Other Names: risperidone( Risperdal), zotepine( Lodopine)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Delirium rating scale	1/2 day, then every 24 hours

Secondary Outcome Measures

Outcome Measure	Time Frame
MMSE, CGI, side effect profile, HRV	12 hours, then every 24 hours

Collaborators and Investigators

• Sponsor: Changhua Christian Hospital
• Investigators: Principal Investigator: Cheng-Chen Chang, M.D., Changhua Christian Hospital

Publications and helpful links

General Publications

• Boettger S, Breitbart W. Atypical antipsychotics in the management of delirium: a review of the empirical literature. Palliat Support Care. 2005 Sep;3(3):227-37. doi: 10.1017/s1478951505050352.

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2008
• Primary Completion (Actual): March 1, 2009
• Study Completion (Actual): March 1, 2009

Study Registration Dates

• First Submitted: January 31, 2008
• First Submitted That Met QC Criteria: February 11, 2008
• First Posted (Estimate): February 22, 2008

Study Record Updates

• Last Update Posted (Actual): February 17, 2020
• Last Update Submitted That Met QC Criteria: February 13, 2020
• Last Verified: February 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Nervous System Diseases; Neurologic Manifestations; Confusion; Neurobehavioral Manifestations; Neurocognitive Disorders; Delirium; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Antipsychotic Agents; Tranquilizing Agents; Psychotropic Drugs; Serotonin Agents; Dopamine Agents; Serotonin Antagonists; Dopamine Antagonists; Risperidone; Zotepine
• Other Study ID Numbers: CCH070906; CCH grant