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

Bipolar Disorder Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01191918
• Other study ID #: Zlu001
• Status: Completed
• Phase: Phase 4
• First received: August 29, 2010
• Last updated: August 30, 2010
• Start date: May 2005
• Est. completion date: April 2008

Study information

• Verified date: August 2010
• Source: Shanghai Mental Health Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: China: Ministry of Health
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 40
• Est. completion date: April 2008
• Est. primary completion date: April 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 60 Years

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Bipolar Disorder
• Mania

Intervention

Drug:
• Donepezil and Lithium
Donepezil dose will be started at 5mg/d and increased to 10 mg/d in 1 week.
• Placebo plus Lithium

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Shanghai Mental Health Center	The Davis Foundations

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Total score change of Young Mania Rating Scale	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	No
Secondary	Treatment Emergent Symptom Scale	assessed at day 1, week1, week 2, week4	from baseline to week4	Yes
Secondary	Clinical Global Impression	assessed at 0h, 2h,4h,6h,8h,10h,12h,24h,week1, week2, week4	frome baseline to week 4	No
Secondary	Brief Psychiatric Rating Scale	assessed at 0h, 2h,4h,6h,8h,10h,12h,24h,week1, week2, week4	frome baseline to week 4	No