Cited by 240Treatment of Major DepressionMental Health Treatment and AccessAnxiety, Depression, Psychometrics, Treatment, Cognitive Processes

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Side effects of antidepressants during long-term use in a naturalistic setting

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Bet, Pierre M., Hugtenburg, Jacqueline G., Penninx, Brenda W.J.H., Hoogendijk, Witte J.G.·2013·European Neuropsychopharmacology

DOI 10.1016/j.euroneuro.2013.05.001

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Abstract

Side effects of antidepressants are usually underreported in clinical trials and large scale naturalistic studies are restricted to six months of use. We examined the prevalence and nature of patient-perceived side effects and their determinants during long-term antidepressant use in a naturalistic setting. Subjects, aged 19 to 67 years, in the Netherlands Study of Depression and Anxiety were recruited from primary care and specialized mental health care covered 927 cases of single antidepressant use. In 64% of cases, on average, 2.9 side effects were reported. The number of side effects was higher when subjects had higher depression severity (OR=1.28; p=0.002), three or more psychiatric diagnoses (OR=1.97; p=0.02), higher dose (OR=1.44; p=0.006) and was lower when subjects were older (OR=0.83; p=0.02) and had longer duration of use (OR=0.94; p=0.04). Tricyclic antidepressants were associated with more side effects (OR=2.52; p=0.003) and, particularly, more anticholinergic effects, like dry mouth and constipation, as compared to selective serotonin reuptake inhibitors. Venlafaxine showed more profuse sweating (OR=1.79; p=0.007), whereas mirtazapine showed more weight gain and less sexual dysfunction (OR=0.36; p=0.03), as compared to selective serotonin reuptake inhibitors. Weight gain was associated with female gender (OR=1.76; p=0.004) and duration of use (OR=1.06; p=0.03). We show that antidepressant side effect, known from short-term studies, persist during long-term use and are associated with depression severity and antidepressant dose. A novel finding was that venlafaxine is associated with more profuse sweating and that weight gain appeared more specific in female users. Clinicians should be aware that, during long-term antidepressant use, side effects are common and persistent.

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Authors: Bet, P. M., Hugtenburg, J. G., Penninx, B. W. J. H., & Hoogendijk, W. J. G.
Affiliations: Amsterdam Neuroscience (NL)
Amsterdam Public Health (NL)
University Medical Center Groningen (NL)
Erasmus MC (NL)
Corresponding author: Bet, Pierre M.
ORCID: Bet, Pierre M.
Hugtenburg, Jacqueline G.
Penninx, Brenda W.J.H.
Hoogendijk, Witte J.G.
Venue: European Neuropsychopharmacology
Publisher: Elsevier BV
Published: 2013-11
Volume: 23
Issue: 11
Pages: 1443-1451
ISSN: 0924-977X (ISSN-L)
DOI: 10.1016/j.euroneuro.2013.05.001
OpenAlex: W2080820439
Cited by: 239
References: 38
Citations by year: 2026: 18 · 2025: 15 · 2024: 22 · 2023: 18 · 2022: 20 · 2021: 24 · 2020: 22 · 2019: 18 · 2018: 17 · 2017: 17 · 2016: 24 · 2015: 11 · 2014: 13
FWCI: 11.75
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: European Neuropsychopharmacology (publishedVersion)
PubMed (publishedVersion)
Amsterdam UMC (VU Amsterdam) - Institutional Repository (publishedVersion)
EUR Research Repository (Erasmus University Rotterdam) (publishedVersion, other-oa)
VU Research Portal (publishedVersion)
EUR Research Repository (Erasmus University Rotterdam) (submittedVersion, other-oa)
RePub (Erasmus University Rotterdam) (submittedVersion, other-oa)
Data Archiving and Networked Services (DANS) (submittedVersion)
Leiden Repository (Leiden University) (submittedVersion)
Pure Amsterdam UMC (submittedVersion)
University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion)
Topics: Health Sciences › Medicine › Pharmacology (medical) › Treatment of Major Depression
Health Sciences › Medicine › Psychiatry and Mental health › Mental Health Treatment and Access
Social Sciences › Psychology › Experimental and Cognitive Psychology › Anxiety, Depression, Psychometrics, Treatment, Cognitive Processes
Keywords: antidepressant side effects, long-term antidepressant use, tricyclic antidepressants, selective serotonin reuptake inhibitors, venlafaxine, mirtazapine, anticholinergic effects, weight gain, sexual dysfunction, depression severity, antidepressant dose, sex differences, NESDA
MeSH terms: Adult, Aged, Aging, Antidepressive Agents, Tricyclic, Dose-Response Relationship, Drug, Female, Humans, Longitudinal Studies, Male, Middle Aged, Netherlands, Severity of Illness Index, Time Factors, Selective Serotonin Reuptake Inhibitors, Young Adult

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