Investigation of a Combination Treatment of Escitalopram and rTMS

Investigation of Efficacy and Response Speed of a Combination Treatment of Escitalopram and Repetitive Transcranial Magnetic Stimulation

We intend to test in a randomized, rater blinded, placebo controlled, prospective study the primary hypothesis that an escitalopram-rTMS-combination treatment is more efficacious in the treatment of refractory major depression assessed with the Hamilton Depression Rating Scale

We intend to test in a randomized, rater blinded, placebo controlled, prospective study the primary hypothesis that an escitalopram-rTMS-combination treatment is more efficacious in the treatment of refractory major depression assessed with the Hamilton Depression Rating Scale compared to placebo.

A second hypothesis is that the treatment of MDE with escitalopram (that means in the "Placebo group") alone lead to typical changes like

• An increase in neurotrophic factors concentration (measured by blood concentrations of nerve growth factor (NGF) and brain derived nerve growth factor (BDNF),
• An increase in hippocampal metabolites (measured with magnetic resonance spectroscopy (MRS
• An increase in motor cortical inhibitory activity (measured with motor evoked potentials (MEP
• An increase in serotonergic activity (measured with EEG parameters, Moreover, it is hypothesized that similar but pronounced changes occur in the group treated with the combination treatment.

Inclusion Criteria:

• Major Depressive Episode (according to DSM IV standards)
• HAMD > 20
• Patient has an IQ > 70 based on the investigator´s judgement
• Patient is male or nonpregnant female adequately protected from conception
• Patient is able to comply with all testing and follow-up visit requirements defined by the study protocol
• Patient has voluntarily signed an informed consent in accordance with institutional policies

Exclusion Criteria:

• Patient has a history of schizophrenia, schizoaffective disorder or delusional disorder
• Patient currently has a secondary diagnosis of, or signs of, delirium, dementia, amnestic or other cognitive disorder per DSM IV
• Patient is suicidal
• Patient has had an alcohol or substance dependence within the previous 12 month
• Patient is currently enrolled in another investigational study
• Patient has a history of, or evidence of, significant central nervous disease (especially seizures)
• Patient has previously been treated with escitalopram
• Contraindication against escitalopram or rTMS