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

This study has been completed.
Sponsor:
Collaborator:
The Davis Foundations
Information provided by:
Shanghai Mental Health Center
ClinicalTrials.gov Identifier:
NCT01191918
First received: August 29, 2010
Last updated: August 30, 2010
Last verified: August 2010
  Purpose

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.


Condition Intervention Phase
Bipolar Disorder
Mania
Drug: Donepezil and Lithium
Drug: Placebo plus Lithium
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Double-Blind, Placebo-Controlled Evaluation of The Efficacy and Safety of AChE Inhibitor Donepezil As Adjunctive Treatment to Mood Stabilizers in Acute Mania

Resource links provided by NLM:


Further study details as provided by Shanghai Mental Health Center:

Primary Outcome Measures:
  • Total score change of Young Mania Rating Scale [ Time Frame: from baseline to week 4 ] [ Designated as safety issue: No ]
    Patients were assessed by outcomes assessores at 0 hour(h), 2h,4h,6h,8h,10h,12h,24h,1 week (w), 2w, 4w


Secondary Outcome Measures:
  • Treatment Emergent Symptom Scale [ Time Frame: from baseline to week4 ] [ Designated as safety issue: Yes ]
    assessed at day 1, week1, week 2, week4

  • Clinical Global Impression [ Time Frame: frome baseline to week 4 ] [ Designated as safety issue: No ]
    assessed at 0h, 2h,4h,6h,8h,10h,12h,24h,week1, week2, week4

  • Brief Psychiatric Rating Scale [ Time Frame: frome baseline to week 4 ] [ Designated as safety issue: No ]
    assessed at 0h, 2h,4h,6h,8h,10h,12h,24h,week1, week2, week4


Enrollment: 40
Study Start Date: May 2005
Study Completion Date: April 2008
Primary Completion Date: April 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: Aricept
Placebo Comparator: Control
Placebo plus Lithium
Drug: Placebo plus Lithium

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.

  Eligibility

Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01191918

Sponsors and Collaborators
Shanghai Mental Health Center
The Davis Foundations
Investigators
Principal Investigator: Zhen Lu, MD Shanghai Mental Health Center
  More Information

No publications provided

Responsible Party: Zheng Lu, Shanghai Mental Health Center, Shanghai Jiaotong University School of Medicine
ClinicalTrials.gov Identifier: NCT01191918     History of Changes
Other Study ID Numbers: Zlu001
Study First Received: August 29, 2010
Last Updated: August 30, 2010
Health Authority: China: Ministry of Health

Keywords provided by Shanghai Mental Health Center:
acetylcholinesterase inhibitor
donepezil
bipolar disorder
mania
lithium

Additional relevant MeSH terms:
Bipolar Disorder
Affective Disorders, Psychotic
Mood Disorders
Mental Disorders
Donepezil
Lithium
Lithium Carbonate
Cholinesterase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Cholinergic Agents
Neurotransmitter Agents
Physiological Effects of Drugs
Nootropic Agents
Central Nervous System Agents
Therapeutic Uses
Antipsychotic Agents
Tranquilizing Agents
Central Nervous System Depressants
Psychotropic Drugs
Antimanic Agents
Antidepressive Agents

ClinicalTrials.gov processed this record on September 18, 2014