Inclusion Criteria:

1. Have signed written informed consent
2. Be male and/or female outpatients 18 65 years of age, inclusive
3. For women: must be surgically sterile, 2 years postmenopausal, or, if they have childbearing potential, using a medically accepted method of birth control and agree to continue use of this method for at least 30 days after the last dose of study drug (i.e., barrier method with spermicide, steroidal contraceptive or intrauterine device [IUD])
4. Meet DSM IV1 criteria for major depressive episode (unipolar), with atypical features
5. Have a score of 20 or greater on the Hamilton Depression Rating, 28-item version (HAM-D-28)
6. Have a complete medical and psychiatric history, physical examination, laboratory evaluation, and ECG before study entry.
7. Have baseline laboratory values and ECG that are normal, or abnormalities that are clinically insignificant

Exclusion Criteria:

1. Have significant and/or unstable gastrointestinal, neurological, endocrine, cardiovascular, pulmonary, renal, hepatic, immunological or hematological disease; organic brain disease; or cancer as determined by history, physical, ECG, and laboratory examination
2. Have a history of peptic ulcer disease
3. Have a history of severe asthma
4. Have a current diagnosis of pheochromocytoma
5. Are pregnant, intending to become pregnant, nursing, at risk for pregnancy, or not practicing medically acceptable birth control. (A blood pregnancy test will be performed at the screening visit)
6. Meet criteria for DSM IV1 psychoactive substance abuse or dependence in the past month
7. Have a history of a psychotic disorder
8. Use any medications that, in the judgment of the investigator, might have psychotropic effects, or interact unfavorably with betahistine dihydrochloride including centrally acting antihistaminic agents
9. Have a history of hypersensitivity to betahistine dihydrochloride
10. Exhibit, or suggestion that they may display, behavior that will not be conducive to the study procedures
11. Are at significant risk of suicide as indicated by a score of 3 or greater on item number 11 on the HAM-D 28
12. Have received any investigational product within 28 days of Screening
13. Have used any antidepressant within 7 days of Screening (14 days for MAOIs; 21 days for fluoxetine)