Antidepressant Plus Asenapine Versus Antidepressant Plus Placebo for Depression

The investigators will undertake a 6-week, double-blind, randomized, parallel-group, placebo-controlled trial of adjunctive asenapine in 130 patients with MDD without psychosis who have had an incomplete therapeutic response to treatment with an antidepressant medication alone.

Inclusion criteria

-130 male or female patients, 18-65 years of age, with:

• DSM-IV diagnosis of MDD without psychosis (single episode or recurrent) confirmed by the Mini-International Neuro-psychiatric Interview (MINI)
• MADRS total score > 20, and item 1 (Apparent Sadness) score > 2 at enrollment and randomization
• 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

• 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
• DSM-IV Axis II diagnoses that significantly impact the current psychiatric status
• Current MDD episode lasting > 12 months
• Electroconvulsive therapy within the preceding 6 months
• Substance or alcohol dependence, as defined by DSM-IV criteria, within 6 months prior to enrollment
• Unstable medical illness, epilepsy, traumatic brain injury, Parkinson disease, or dementia (MMSE <24)
• Risk of suicide as defined by MADRS item 10 score > 4
• Prior failure to respond to asenapine
• Pregnancy or failure to use an acceptable form of birth control. Pregnancy as determined by serum pregnancy test at baseline
• Hepatic impairment and history of low WBC, by medical history and interview.