60 patients with chronic major depressive disorder according to DSM-IV will be included into the study. Patients will be randomized to receive an open treatment either with CBASP, a psychotherapy for chronic depression, or pharmacological treatment with Escitalopram for 28 weeks.

The psychotherapeutic treatment with CBASP will be conducted in 2 weekly sessions for the first 4 weeks, one per week thereafter until week 9, followed by one session every 2 weeks for 20 more weeks. The starting dose for Escitalopram will be 10 mg/d for one week and will be increased to 20 mg/d after one week. The dosage can be reduced to 10 mg/d after day 7 to improve tolerance. Th MADRS-scale is the primary outcome measure; ratings will be performed by a blinded rater. If there is no improvement (reduction of less than 20% of the MADRS), patients will be crossed over in terms of adding the other treatment at week 8. Study patients will be asked to participate in fMRI, genetic and pharmacological substudies.

Inclusion Criteria:

• Chronic MDD according to DSM-IV (modification: depressive symptomatology for at least one year), or recurrent MDE (third or greater episode with the immediately preceding episode being no more than 2.5 years before the onset of the present episode)
• Age 18-65
• Score of at least 18 on the Montgomery-Asberg-Rating Scale for Depression (MADRS)

Exclusion Criteria:

• Acute risk for suicide
• History of psychotic symptoms, bipolar disorder or dementia
• Severe substance-related abuse or dependence disorder
• Schizotypal, antisocial or borderline personality disorder
• Serious medical condition
• Severe cognitive impairment
• Absence of a response to previous adequate trial of the study medication/CBASP
• Hypersensitivity to Escitalopram
• Treatment with a MAO-inhibitor within 1 week before the initiation of study treatment