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Cited by 49Treatment of Major DepressionSalivary Gland Disorders and FunctionsPharmacology and Obesity Treatment

Meta-analysis: Risk of dry mouth with second generation antidepressants

Cappetta, Kiley, Beyer, Chad, Johnson, Jessica A., Bloch, Michael H.·2018·Progress in Neuro-Psychopharmacology and Biological Psychiatry
DOI 10.1016/j.pnpbp.2017.12.012
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Abstract

Objective: The goal of this meta‐analysis was to quantify the risk of dry mouth associated with commonly prescribed antidepressant agents and examine the potential implications of medication class, dose, and pharmacodynamics and dose on risk of treatment‐induced dry mouth. Data sources and study selection: A PubMed search was conducted to identify double‐blind, randomized, placebo‐controlled trials examining the efficacy and tolerability of second generation antidepressant medications for adults with depressive disorders, anxiety disorders, and OCD. Data extraction: A random‐effects meta‐analysis was used to quantify the pooled risk ratio of treatment‐emergent dry mouth with second generation antidepressants compared to placebo. Stratified subgroup analysis and meta‐regression was utilized to further examine the effects antidepressant agent, class, dosage, indication, and receptor affinity profile on the measured risk of dry mouth. Results: 99 trials involving 20,868 adults. SNRIs (Relative Risk (RR) = 2.24, 95% Confidence Interval (CI): 1.95–2.58, z = 11.2, p < 0.001) were associated with a significantly greater risk of dry mouth (test for subgroup differences χ2 = 7.6, df = 1; p = 0.006) compared to placebo than SSRIs (RR = 1.65, 95% CI: 1.39–1.95, z = 5.8, p < 0.001). There was a significant difference found in the risk of dry mouth between diagnostic indications within the SNRI class (test for subgroup differences χ2 = 9.63, df = 1; p = 0.002). Anxiety diagnoses (RR = 2.78, 95% CI: 2.29–3.38, z = 10.32, p < 0.001) were associated with a greater risk of dry mouth compared to depression (RR = 1.80, 95% CI: 1.48–2.18, z = 5.85, p < 0.001). Decreased affinity for Alpha‐1 (PE = 0.18, 95% CI: 0.07–0.28, z = 3.26, p = 0.001) and Alpha‐2 (PE = 0.49, 95% CI: 0.22–0.75, z = 3.64, p < 0.001) receptors and SERT (PE = 0.07, 95% CI: 0.01–0.14, z = 2.10, p < 0.05) was significantly associated with increased risk of dry mouth. Conclusions: The current meta‐analysis suggests that SSRIs, SNRIs, and atypical antidepressants are all associated with varying degrees of increased risk of dry mouth. SNRIs were associated with a significantly greater risk of dry mouth compared to SSRIs. HIGHLIGHTSMeta‐analysis suggests that SSRIs, SNRIs, and atypical antidepressants are all associated with increased risk of dry mouthSNRIs were associated with a significantly greater risk of dry mouth compared to SSRIsIncreased risk of dry mouth was associated with increased affinity for the serotonin transporter.

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Crossref · 10.1016/j.pnpbp.2017.12.012

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171 of 171 references verified0 citation errors · 0 not checkable

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  • SNRIs exhibited a moderately higher risk of dry mouth compared to placebo than SSRIs did.

    “SNRIs exhibited a moderately higher risk of dry mouth compared to placebo than SSRIs did.”

    From Addressing the Side Effects of Contemporary Antidepressant Drugs: A Comprehensive Review (2018) · cites this paper as [34]

  • SSRIs might have had less risk of dry mouth because of their lower affinity for muscarinic cholinergic receptors, alpha-2 receptors, and norepinephrine.

    “The SSRIs might have had less risk of dry mouth because of their lower affinity for muscarinic cholinergic receptors, alpha-2 receptors, and norepinephrine.”

    From Addressing the Side Effects of Contemporary Antidepressant Drugs: A Comprehensive Review (2018) · cites this paper as [34]

  • A recent meta-analysis including 99 RCTs with SSRIs, SNRIs, and atypical antidepressants showed that all antidepressants increased dry mouth compared with placebo.

    “This recent metaanalysis which included 99 RCTs with SSRIs, SNRIs, and atypical antidepressants showed that all antidepressant increased dry mouth compared with placebo.”

    From Addressing the Side Effects of Contemporary Antidepressant Drugs: A Comprehensive Review (2018) · cites this paper as [34]

  • The central accumulation of norepinephrine from SNRIs might have activated alpha-2 receptors and concurrent inhibition of parasympathetic salivary neurons in the brainstem, which lead to decreased salivary flow and dry mouth.

    “The central accumulation of norepinephrine from SNRIs might have activated alpha-2 receptors and concurrent inhibition of parasympathetic salivary neurons in the brainstem, which lead to decreased salivary flow and dry mouth.3435”

    From Addressing the Side Effects of Contemporary Antidepressant Drugs: A Comprehensive Review (2018) · cites this paper as [34]

  • Meta-regression analysis restricted to SSRIs and SNRIs did not indicate a significant association between M3 receptor affinity and risk of dry mouth.

    “However, meta-regression analysis restricted to SSRIs and SNRIs did not indicate a significant association between M3 receptor affinity and risk of dry mouth.34”

    From Addressing the Side Effects of Contemporary Antidepressant Drugs: A Comprehensive Review (2018) · cites this paper as [34]

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Authors
Cappetta, K., Beyer, C., Johnson, J. A., & Bloch, M. H.
Affiliations
Yale University (US)
Corresponding author
Bloch, Michael H.
ORCID
Venue
Progress in Neuro-Psychopharmacology and Biological Psychiatry
Publisher
Elsevier BV
Published
2018-06
Volume
84
Issue
Pt A
Pages
282-293
ISSN
0278-5846 (ISSN-L)
DOI
10.1016/j.pnpbp.2017.12.012
OpenAlex
W2778099882
Semantic Scholar
93adb2d56f5e5a609e89c85820fd994a2c472063
Cited by
49
References
176
Citations by year
2026: 6 · 2025: 7 · 2024: 7 · 2023: 7 · 2022: 9 · 2021: 6 · 2020: 5 · 2019: 1 · 2018: 1
FWCI
1.34
Type
journal article
Language
en
Open access
closed
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Progress in Neuro-Psychopharmacology and Biological Psychiatry (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
  • Health Sciences › Medicine › Physiology › Salivary Gland Disorders and Functions
  • Health Sciences › Medicine › Pharmacology › Pharmacology and Obesity Treatment
Keywords
xerostomia, second-generation antidepressants, selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, antidepressant side effects, anxiety disorders, depression, obsessive-compulsive disorder, dose-response relationship
MeSH terms
Humans, Risk, Xerostomia, Antidepressive Agents, Second-Generation

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