Cognitive Flexibility in Major Depression in the Course of Pharmacological and Psychotherapeutic Treatment

Study Overview
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Brief Summary
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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.

Detailed Description
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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).

Official Title
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Cognitive Flexibility and Its Correlation to Sleep and Neuroplasticity In The Course Of Depression During Different Treatments

Conditions
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Cognitive Performance in Major Depression

Intervention / Treatment
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* Drug: citalopram
* Drug: reboxetine
* Behavioral: interpersonal psychotherapy


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Selective serotonin reuptake inhibitor (SSRI)<br>citalopram | Drug: citalopram<br>* 20 to 30 mg per day for 4 weeks<br>|
| Experimental: Serotonin-norepinephrine reuptake inhibitor (SNRI)<br>reboxetine | Drug: reboxetine<br>* 4 to 8 mg per day for 4 weeks<br>|
| Active Comparator: IPT<br>interpersonal psychotherapy | Behavioral: interpersonal psychotherapy<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| cognitive performance with respect to cognitive flexibility, memory and attention |  | 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| CREB-phosphorylation in T-Lymphocytes |  | 4 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Depression, CREB, cognitive performance, psychotherapy, SSRI, SNRI