Cited by 72Treatment of Major DepressionPharmacovigilance and Adverse Drug ReactionsElectroconvulsive Therapy Studies

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Tolerability of Serotonin Norepinephrine Reuptake Inhibitor Antidepressants

Montgomery, Stuart A.·2008·CNS Spectrums

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Abstract

All three serotonin norepinephrine reuptake inhibitors (SNRIs) inhibit the reuptake of both serotonin and norepinephrine but they do so with differing affinity ratios. Venlafaxine has a 30-fold higher affinity for serotonin than for norepinephrine while duloxetine has a 10-fold selectivity for serotonin. Milnacipran has a balanced (1:1) ratio of potency for inhibition of reuptake of the two neurotransmitters. The most frequent adverse event with SNRIs is nausea. Not unexpectedly, adverse effects related to a noradrenergic stimulation, such as dry mouth, sweating, and constipation, are found more frequently with SNRIs than with selective serotonin reuptake inhibitors. At true SNRI doses, venlafaxine is associated with dose-dependent cardiovascular phenomena (principally increased blood pressure), an effect which is less frequent with duloxetine and rare with milnacipran. Serious and potentially fatal hepatotoxity has been reported with duloxetine. This problem appears to be unique to duloxetine and not a characteristic of the SNRI class. There are differences in overdose toxicity between venlafaxine and the other SNRIs, possibly related to its increased cardiotoxicity.

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Authors: Montgomery, S. A.
Affiliations: University of London (GB)
Corresponding author: Montgomery, Stuart A.
ORCID: Montgomery, Stuart A.
Venue: CNS Spectrums
Publisher: Cambridge University Press (CUP)
Published: 2008-07
Volume: 13
Issue: S11
Pages: 27-33
ISSN: 1092-8529 (ISSN-L)
2165-6509
DOI: 10.1017/s1092852900028297
OpenAlex: W2125788603
Cited by: 65
References: 0
Citations by year: 2026: 6 · 2025: 4 · 2024: 4 · 2023: 4 · 2022: 1 · 2021: 2 · 2020: 3 · 2019: 4 · 2018: 6 · 2017: 2 · 2016: 5 · 2015: 3 · 2014: 5 · 2013: 3 · 2012: 5
FWCI: 1.87
Type: journal article
Language: en
Open access: closed
Licence: www.cambridge.org/core/terms (unspecified, 2320 d)
Locations: CNS Spectrums (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Pharmacology (medical) › Treatment of Major Depression
Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Toxicology › Pharmacovigilance and Adverse Drug Reactions
Health Sciences › Medicine › Psychiatry and Mental health › Electroconvulsive Therapy Studies
Keywords: serotonin-norepinephrine reuptake inhibitors, antidepressant tolerability, venlafaxine, duloxetine, milnacipran, nausea, blood pressure increase, cardiotoxicity
MeSH terms: Cardiovascular Diseases, Depression, Dose-Response Relationship, Drug, Drug Interactions, Drug Tolerance, Humans, Sexual Dysfunction, Physiological, Substance Withdrawal Syndrome, Selective Serotonin Reuptake Inhibitors, Adrenergic Uptake Inhibitors, Chemical and Drug Induced Liver Injury

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Tolerability of Serotonin Norepinephrine Reuptake Inhibitor Antidepressants

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