The Efficacy and Safety of AChE Inhibitor Donepezil As Adjunctive Treatment to Mood Stabilizers in Acute Mania

August 30, 2010 updated by: Shanghai Mental Health Center

A Double-Blind, Placebo-Controlled Evaluation of The Efficacy and Safety of AChE Inhibitor Donepezil As Adjunctive Treatment to Mood Stabilizers in Acute Mania

There is a high rate of partial response to standard thymoleptic medication. In this study the investigators want to evaluate the safety and efficacy of donepezil as adjunctive treatment to mood stabilizers in bipolar disorder with acute mania. The investigators hypotheses were that there would be greater mean reduction in manic symptoms with donepezil augmentation of lithium compared with placebo.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Bipolar disorder is a chronic mental illness that affects 1-2% of the general population. Lithium and valproate are effective for treatment of acute mania for many patients. However up to half of patients do not respond adequately to currently approved treatments in the acute phase of mania. More effective treatment for mania are need. Imbalance in cholinergic and adrenergic tone has long been postulated in the pathophysiology of bipolar disorder. In the pathophysiology of mania,relative cholinergic hypoactivity was being implicated. Donepezil is a centrally acting reversible acetylcholinesterase inhibitor. It is approved for the treatment of Alzheimer's disease. In an open case series with standardized ratings, addition of donepezil 5-10 mg/day to ongoing mood-stabilizer treatment was associated with marked improvement in treatment-resistant mania. We want to conduct a 4-week randomized, double-blind, placebo-controlled trial of donepezil as augmentation of lithium in patients with acute manic episode to evaluate the safety and efficacy of donepezil as adjunctive treatment to mood stabilizers in bipolar disorder with acute mania.

Study Type

Interventional

Enrollment (Actual)

40

Phase

  • Phase 4

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years to 58 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Patients have DSM-IV diagnosis of bipolar disorder with acute manic episode who are admitted as inpatient
  2. Young Mania Rating Scale (YMRS) total score >20 (based on mean scores of two ratings after admission)
  3. Physical examination, laboratory results (eg.EKG) from screening visit normal, or abnormal clinically insignificant

Exclusion Criteria:

  1. Having history of allergy to donepezil or Lithium.
  2. Having active suicide or homicide attempt or intent
  3. Having severe medical conditions or taking multiple medications for medical conditions
  4. Investigational drug treatment within past 30 days
  5. Having a drug screen positive for any drug of abuse at screening
  6. Self-report of active substance abuse in the past 2 weeks or substance dependence in the past 2 months
  7. Diagnosis of schizophrenia, dementia, delirium, seizure disorder, obsessive compulsive disorder, or unstable medical condition
  8. Administration of any investigational drug within 30 days of screening
  9. Pregnancy or lactation
  10. Asthma requiring chronic medication treatment or ongoing use of anticholinergic medications or cholinomimetics
  11. Other factors that investigator consider not suitable for the study

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: donepezil
donepezil plus Lithium
Drug: Donepezil and Lithium
Donepezil dose will be started at 5mg/d and increased to 10 mg/d in 1 week.
Other Names:
  • Aricept
Placebo Comparator: Control
Placebo plus Lithium
Drug: Placebo plus Lithium

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Total score change of Young Mania Rating Scale
Time Frame: from baseline to week 4
Patients were assessed by outcomes assessores at 0 hour(h), 2h,4h,6h,8h,10h,12h,24h,1 week (w), 2w, 4w
from baseline to week 4

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Treatment Emergent Symptom Scale
Time Frame: from baseline to week4
assessed at day 1, week1, week 2, week4
from baseline to week4
Clinical Global Impression
Time Frame: frome baseline to week 4
assessed at 0h, 2h,4h,6h,8h,10h,12h,24h,week1, week2, week4
frome baseline to week 4
Brief Psychiatric Rating Scale
Time Frame: frome baseline to week 4
assessed at 0h, 2h,4h,6h,8h,10h,12h,24h,week1, week2, week4
frome baseline to week 4

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Shanghai Mental Health Center

Collaborators

The Davis Foundations

Investigators

  • Principal Investigator: Zhen Lu, MD, Shanghai Mental Health Center

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

May 1, 2005

Primary Completion (Actual)

April 1, 2008

Study Completion (Actual)

April 1, 2008

Study Registration Dates

First Submitted

August 29, 2010

First Submitted That Met QC Criteria

August 30, 2010

First Posted (Estimate)

August 31, 2010

Study Record Updates

Last Update Posted (Estimate)

August 31, 2010

Last Update Submitted That Met QC Criteria

August 30, 2010

Last Verified

August 1, 2010

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Zlu001

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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