Major depressive disorder was shown to be associated with pathological alterations within neurotransmitter systems of the brain. Based on earlier study results, it is assumed that the neurotransmitter dopamine is relevant for several symptoms of depression, e.g., loss of interest or pleasure and lack of motivation. Thus, it is assumed that the synthesis of dopamine in the brain of depressed individuals could be impaired. The specific effect of common antidepressants on the human reward system in depression has not yet been sufficiently investigated. In particular, it is unclear whether depressed patients exhibit reward-specific changes of dopamine synthesis, and whether or not these changes can be differentially affected by diverse types of antidepressants. Neurotransmitter systems can be visualized in the brain using positron emission tomography (PET). Additionally, brain structure and function can be studied using magnetic resonance imaging (MRI). For the visualization of dopamine synthesis in the brain, the radioligand \[18F\]FDOPA can be used in PET measurements. To assess task-relevant changes of diverse radioligands and thus specific metabolic processes in the brain during specific tasks, a recently developed PET-approach can be used which has already been successfully applied in a pilot study with healthy volunteers. In the present project, 60 depressed subjects and 30 healthy controls will undergo PET/MR-imaging twice. Depressed subjects will be assigned to 1 of 2 treatment groups. 30 depressive subjects will receive bupropion, the other 30 patients will be treated with escitalopram. After a treatment period of 6 weeks, the 2nd PET measurement will be performed in all participants, aiming to detect potential reward-specific changes of dopamine synthesis. The investigators hypothesize that reward-specific changes of dopamine synthesis will be lower in depressed subjects than in healthy controls, that reward-specific changes of dopamine synthesis will be significantly higher in the bupropion group than in the escitalopram group, and that the changes of dopamine synthesis will be associated with functional changes in the brain (measured by simultaneous functional MRI scans). This will be the first study comparing the effects of escitalopram and bupropion on task-specific dopamine synthesis and thus on the human reward system. The study is expected to yield new insights for individual treatment concepts in the therapy of depression.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
120
Bupropion 150 mg daily after baseline PET/MRI or MRI/MRS over 6-8 weeks
Escitalopram 10 mg daily after baseline PET/MRI or MRI/MRS over 6-8 weeks
Medical University of Vienna
Vienna, Austria
RECRUITINGChanges of the reward specific dopamine synthesis rate in the nucleus accumbens of depressed individuals after 6-8 weeks of antidepressant intake assessed via functional PET
Reward-specific dopamine synthesis rate: Assessment of the net influx constant Ki in the nucleus accumbens via functional PET using \[18F\]FDOPA as an index of the dopamine synthesis rate
Time frame: 6-8 weeks
Relationship between potential changes of the reward-specific dopamine synthesis rate in the nucleus accumbens assessed via functional PET and treatment response in depressed individuals after 6-8 weeks of antidepressant intake
Reward-specific dopamine synthesis rate: Assessment of the net influx constant Ki in the nucleus accumbens via functional PET using \[18F\]FDOPA as an index of the dopamine synthesis rate; Treatment response rates will be assessed at baseline and after 6-8 weeks of antidepressant therapy via the Hamilton Depression Rating Scale with 29 items (HDRS29) and the Montgomery-Åsberg Depression Rating Scale (MADRS).
Time frame: 6-8 weeks
Difference in changes to the reward-specific dopamine synthesis rate in the nucleus accumbens assessed via functional PET in depressed patients taking bupropion vs. escitalopram after 6-8 weeks of therapy
Reward-specific dopamine synthesis rate: Assessment of the net influx constant Ki in the nucleus accumbens via functional PET using \[18F\]FDOPA as an index of the dopamine synthesis rate
Time frame: 6-8 weeks
Relationship between the reward-specific dopamine synthesis rate (assessed via functional PET) and fMRI activation across healthy volunteers and depressed patients, both at baseline and after 6-8 weeks of therapy
Reward-specific dopamine synthesis rate: Assessment of the net influx constant Ki in the nucleus accumbens via functional PET using \[18F\]FDOPA as an index of the dopamine synthesis rate; fMRI activation: Blood-Oxygenation-Level Dependent Signal via functional Magnetic Resonance Imaging
Time frame: 6-8 weeks
Remission rates in depressed patients being treated with either escitalopram or bupropion in a longitudinal design
Remission rates will be assessed at baseline and after 6-8 weeks of antidepressant therapy via the Hamilton Depression Rating Scale with 29 items (HDRS29) and the Montgomery-Åsberg Depression Rating Scale (MADRS).
Time frame: 6-8 weeks
Test-retest reliability for the quantification of dopamine synthesis rates in healthy volunteers via functional PET
Reward-specific dopamine synthesis rate: Assessment of the net influx constant Ki in the nucleus accumbens via functional PET using \[18F\]FDOPA as an index of the dopamine synthesis rate; assessed at baseline and after 6-8 weeks without any interventions in between
Time frame: 6-8 weeks
Rupert Lanzenberger, Univ.-Prof. Priv.-Doz. Dr.
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