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.

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.

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