ArticleThe international journal of neuropsychopharmacology2022
Differential Potency of Venlafaxine, Paroxetine, and Atomoxetine to Inhibit Serotonin and Norepinephrine Reuptake in Patients With Major Depressive Disorder.
Article in The international journal of neuropsychopharmacology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03249311 (Effectiveness of the Norepinephrine and Serotonin Reuptake Inhibitor Levomilnacipran in Healthy Males), which is not on this map. Cited by 11 papers, 2 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Effectiveness of the Norepinephrine and Serotonin Reuptake Inhibitor Levomilnacipran in Healthy Males
Who cites it
11 citing papers in PubMed, 2 syntheses or guidelines pooled it, 20 citations in OpenAlex.
- Efficacy and dose-response relationships of antidepressants in the acute treatment of major depressive disorders: a systematic review and network meta-analysis.Chinese medical journal · 2025Pooled it
- Venlafaxine's therapeutic reference range in the treatment of depression revised: a systematic review and meta-analysis.Psychopharmacology · 2024Pooled it
- Psychopharmacological Mechanisms of Antidepressant Withdrawal: Insights From Venlafaxine.Human psychopharmacology · 2026Review
- Pharmacological Re-Optimization With Venlafaxine in Two Elderly Patients With Severe Major Depressive Disorder Considered for Electroconvulsive Therapy: A Two-Patient Case Report.Clinical case reports · 2026Article
- Analysis of ocular adverse events associated with SNRIs.Frontiers in pharmacology · 2026Article
- Neural signaling mechanisms in depression: bridging classical monoamine hypotheses, animal models, and emerging antidepressant strategies.Frontiers in cell and developmental biology · 2026Review
- Revisiting the Role of Serotonin in Attention-Deficit Hyperactivity Disorder: New Insights from Preclinical and Clinical Studies.Clinical drug investigation · 2025Review
- Does isovaleric acid play a key role in the interaction between probiotics and antidepressants? A secondary analysis of a randomized clinical trial.Computational and structural biotechnology journal · 2025Article
- AMPA receptors modulate enhanced dopamine neuronal activity induced by the combined administration of venlafaxine and brexpiprazole.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2024Article
- Association of inflammation cytokines with cognitive function in first-episode major depressive disorder.Frontiers in psychiatry · 2024Article
- Life-Threatening Cardiogenic Shock Related to Venlafaxine Poisoning-A Case Report with Metabolomic Approach.Metabolites · 2023Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundVenlafaxine is a dual serotonin (5-HT) and norepinephrine reuptake inhibitor. The specific dose at which it begins to efficiently engage the norepinephrine transporter (NET) remained to be determined. Paroxetine is generally considered as a selective 5-HT reuptake inhibitor but exhibits some affinity for NET. Atomoxetine is a NET inhibitor but also has some affinity for the 5-HT reuptake transporter (SERT).
methodsThis study examined the effects of forced titration of venlafaxine from 75 to 300 mg/d, paroxetine from 20 to 50 mg/d, or atomoxetine from 25 to 80 mg/d in 32 patients with major depressive disorder. Inhibition of SERT was estimated using the depletion of whole-blood 5-HT. Inhibition of NET was assessed using the attenuation of the systolic blood pressure produced by i.v. injections of tyramine.
resultsAll 3 medications significantly reduced 5-HT levels at the initiating regimens: venlafaxine and paroxetine by approximately 60% and atomoxetine by 16%. The 3 subsequent regimens of venlafaxine and paroxetine reduced 5-HT levels by over 90%, but the highest dose of atomoxetine only reached a 40% inhibition. Atomoxetine dose dependently inhibited the tyramine pressor response from the lowest dose, venlafaxine from 225 mg/d, and paroxetine left it unaltered throughout.
conclusionThese results confirm that venlafaxine and paroxetine are potent SERT inhibitors over their usual therapeutic range but that venlafaxine starts inhibiting NET only at 225 mg/d, whereas paroxetine remains selective for SERT up to 50 mg/d. Atomoxetine dose dependently inhibits NET from a low dose but does not inhibit SERT to a clinically relevant degree.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.