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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Mania, Bipolar Disorder

Intervention / Treatment
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* Drug: Donepezil and Lithium
* Drug: Placebo plus Lithium


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients have DSM-IV diagnosis of bipolar disorder with acute manic episode who are admitted as inpatient Young Mania Rating Scale (YMRS) total score >20 (based on mean scores of two ratings after admission) Physical examination, laboratory results (eg.EKG) from screening visit normal, or abnormal clinically insignificant Exclusion Criteria: Having history of allergy to donepezil or Lithium. Having active suicide or homicide attempt or intent Having severe medical conditions or taking multiple medications for medical conditions Investigational drug treatment within past 30 days Having a drug screen positive for any drug of abuse at screening Self-report of active substance abuse in the past 2 weeks or substance dependence in the past 2 months Diagnosis of schizophrenia, dementia, delirium, seizure disorder, obsessive compulsive disorder, or unstable medical condition Administration of any investigational drug within 30 days of screening Pregnancy or lactation Asthma requiring chronic medication treatment or ongoing use of anticholinergic medications or cholinomimetics Other factors that investigator consider not suitable for the study

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: donepezil<br>donepezil plus Lithium | Drug: Donepezil and Lithium<br>* Donepezil dose will be started at 5mg/d and increased to 10 mg/d in 1 week.<br>* Other names: Aricept;|
| Placebo Comparator: Control<br>Placebo plus Lithium | Drug: Placebo plus Lithium<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 

Secondary Outcome Measures

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

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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acetylcholinesterase inhibitor, donepezil, bipolar disorder, mania, lithium