Cognitive deficits in major depression seem explicable by the well-recognized concept of impaired neuroplasticity in mood disorders. This concept initially emerged from preclinical evidence that antidepressants phosphorylate and therefore activate the cyclic AMP response element binding protein (CREB) that is essential for synaptic plasticity. Nevertheless, the question remains whether the activation of CREB by antidepressants is relevant for the remission of cognitive deficits in patients. We addressed this issue by investigating the cognitive improvement during treatment with either citalopram or reboxetine because these antidepressants are different in their capacity to increase phosphorylated CREB (pCREB). Besides the pharmacological treatment groups, another group of patients was treated exclusively with psychotherapy.

We randomly assigned forty-five depressive patients to one of three treatment groups (Citalopram, Reboxetin or interpersonal psychotherapy (IPT)). At baseline, day 7 and day 28 we assessed the severity of depression and the cognitive performance with respect to cognitive flexibility, memory and attention. We measured pCREB with an enzyme linked immuno sorbent assay (ELISA).

Inclusion Criteria:

• Diagnosed according DSM-IV criteria as suffering from major depressive disorder
• A baseline score of at least 18 in the Hamilton Depression Scale (HAMD)
• No psychopharmacological treatment at least one week prior inclusion or 3 days wash-out

Exclusion Criteria:

• Severe depressive episode and/or psychotic depressive episode

Axis I disorder:

• Substance-related Disorders
• Psychotic Disorders
• Dementia or other cognitive Disorders
• Obsessive-Compulsive Disorders

Axis II disorder:

• Borderline Personality Disorder

Axis III disorder:

• Infectious Diseases
• Cancer
• Endocrinological Diseases
• Hematological Diseases
• Autoimmune Diseases