Antidepressant Plus Asenapine Versus Antidepressant Plus Placebo for Depression

Inclusion Criteria: -130 male or female patients, 18-65 years of age, with: 1. DSM-IV diagnosis of MDD without psychosis (single episode or recurrent) confirmed by the Mini-International Neuro-psychiatric Interview (MINI) 2. MADRS total score \> 20, and item 1 (Apparent Sadness) score \> 2 at enrollment and randomization 3. Inadequate therapeutic response during their current depressive episode; an inadequate therapeutic response will be defined as continued depressive psychopathology (see criterion 2) following \> six weeks of therapy at adequate doses (according to the US label) of any non-tricyclic, non-MAOI antidepressant medication Exclusion Criteria: 1. Additional DSM-IV Axis I diagnoses other than Generalized Anxiety Disorder, Panic Disorder with or without Agoraphobia, or Social Phobia within 6 months prior to enrollment 2. DSM-IV Axis II diagnoses that significantly impact the current psychiatric status 3. Current MDD episode lasting \> 12 months 4. Electroconvulsive therapy within the preceding 6 months 5. Substance or alcohol dependence, as defined by DSM-IV criteria, within 6 months prior to enrollment 6. Unstable medical illness, epilepsy, traumatic brain injury, Parkinson disease, or dementia (MMSE \<24) 7. Risk of suicide as defined by MADRS item 10 score \> 4 8. Prior failure to respond to asenapine 9. Pregnancy or failure to use an acceptable form of birth control. Pregnancy as determined by serum pregnancy test at baseline 10. Hepatic impairment and history of low WBC, by medical history and interview.