Differential physiological effects of a low dose and high doses of venlafaxine in major depression
Why this work is in the frame
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Bibliographic record
Abstract
Venlafaxine is an antidepressant drug with demonstrated serotonin (5-HT) and norepinephrine (NE) reuptake blockade properties in electrophysiological and microdialysis experiments in laboratory animals. In healthy volunteers, its 5-HT reuptake-inhibiting potential has also been clearly documented, but not its NE reuptake blockade action. This double-blind study compared the effects of a low dose (75 mg) and of a forced titration of high (up to 375 mg in 1 wk) daily doses of venlafaxine. Forty-four patients with major depression according to DSM-IV criteria were assessed bi-weekly for the first 2 wk and weekly for the next 2 wk. Inhibition of 5-HT reuptake was estimated using the depletion of whole-blood 5-HT, while that of NE was assessed using the attenuation of the systolic blood-pressure elevations produced by intravenous injections of tyramine. Forty-two patients completed the study. Both the low and the high doses of venlafaxine decreased the levels of 5-HT to the same extent: the reduction was of about 55% after 1 wk and of 75% after 4 wk. The 75 mg/d dose of venlafaxine did not alter the tyramine pressor response, whereas, in patients receiving the higher regimens of venlafaxine, there was a significant attenuation of the pressor effect of tyramine. There was no significant difference between the two treatment arms regarding the modifications of the depression scores. The present data showed that, at its minimal effective dose in depression (75 mg/d), venlafaxine acted as a selective 5-HT reuptake inhibitor, whereas when administered at higher doses (225 and 375 mg/d), it acted as a dual 5-HT and NE reuptake inhibitor.
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Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| 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) | 0.000 | 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 it