Atomoxetine, but not paroxetine, blocks norepinephrine reuptake in depressed patientss
Bibliographic record
Abstract
Purpose: Paroxetine is a potent serotonin (5-HT) reuptake inhibitor. However, a purported norepinephrine (NE) reuptake blockade action remains to be established. Atomoxetine is a potent NE reuptake inhibitor with the indication of attention deficit hyperactivity disorder (ADHD). The present study was aimed at confirming a NE reuptake inhibitory action with ascending doses of atomoxetine and possibly with paroxetine in depressed patients. Methods: Patients were randomized to escalating doses of either paroxetine (20 to 50 mg/day), or atomoxetine (25-80 mg/day) in a four to six week period. Inhibition of NE reuptake was assessed using the attenuation of systolic blood pressure (SBP) elevations produced by intravenous injections of tyramine. Tyramine penetrates into peripheral NE terminals via the NE reuptake transporter and releases NE. Then, NE acts on the vascular adrenoceptors, which causes an elevation of SBP. Drugs that block NE reuptake attenuate the pressor effects of tyramine. Two-way ANOVA for repeated measures for doses of tyramine and treatments were used to assess the effects of the different drug regimens on the pressor response to loads of 3–6 mg of tyramine. Sixteen patients with unipolar major depressive disorder were assessed weekly after increasing the dose of paroxetine (9 patients) and atomoxetine (7 patients). Results: Atomoxetine exerted a robust inhibition of the tyramine response, starting at the dose of 25mg/day in a dose-dependent pattern. Neither the low nor the high doses of paroxetine altered the tyramine pressor response. Conclusions: These results provide evidence that atomoxetine started significantly inhibiting NE reuptake at subtherapeutic dose for ADHD, whereas paroxetine leaves the activity of the NE transporter unaltered, even at the highest recommended dose for depression.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".