Risks of Digestive System Side-Effects of Selective Serotonin Reuptake Inhibitors in Patients with Depression: A Network Meta-Analysis

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Abstract

Purpose

Selective serotonin reuptake inhibitors (SSRIs) are the preferred treatments for depression. The most common adverse drug reactions are symptoms involving the digestive system, leading to low compliance in patients with depression. Therefore, it is important to assess the safety of SSRIs with respect to the digestive system. Several meta-analyses have compared the risks of digestive side effects of SSRIs and other antidepressants. We aimed to compare the risks of various SSRIs (fluoxetine, escitalopram, citalopram, paroxetine, and sertraline) for adverse reactions of the digestive system.

Methods

Systematic searches returned 30 randomized controlled trials (n = 5004) of five antidepressants and placebos.

Results

Fluoxetine had the lowest probability of digestive side effects, ranking fifth at 0.548. Sertraline had the highest probability of digestive side effects, with a probability of 0.611. For gastrointestinal tolerability, escitalopram was better than paroxetine (odds ratio [OR] =0.62, 95% confidence interval [CI] 0.43–0.87) and sertraline (OR=0.56, 95% CI 0.32–0.99).

Conclusion

Fluoxetine exhibited distinct advantages compared to other SSRIs, while sertraline had the greatest likelihood of digestive system side effects. These findings will help doctors understand the relative advantages of various antidepressants.

Most cited references 67

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Differential effects of psychotropic drugs on microbiome composition and gastrointestinal function

John F. Cryan, Catherine Stanton, Timothy Dinan … (2018)

Growing evidence supports a role for the microbiota in regulating gut-brain interactions and, thus, psychiatric disorders. Despite substantial scientific efforts to delineate the mechanism of action of psychotropic medications at a central nervous system (CNS) level, there remains a critical lack of understanding on how these drugs might affect the microbiota and gut physiology.

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Optimal dose of selective serotonin reuptake inhibitors, venlafaxine, and mirtazapine in major depression: a systematic review and dose-response meta-analysis

Toshi Furukawa, Andrea Cipriani, Philip J. Cowen … (2019)

Summary Background Depression is the single largest contributor to non-fatal health loss worldwide. Second-generation antidepressants are the first-line option for pharmacological management of depression. Optimising their use is crucial in reducing the burden of depression; however, debate about their dose dependency and their optimal target dose is ongoing. We have aimed to summarise the currently available best evidence to inform this clinical question. Methods We did a systematic review and dose-response meta-analysis of double-blind, randomised controlled trials that examined fixed doses of five selective serotonin reuptake inhibitors (SSRIs; citalopram, escitalopram, fluoxetine, paroxetine, and sertraline), venlafaxine, or mirtazapine in the acute treatment of adults (aged 18 years or older) with major depression, identified from the Cochrane Central Register of Controlled Trials, CINAHL, Embase, LILACS, MEDLINE, PsycINFO, AMED, PSYNDEX, websites of drug licensing agencies and pharmaceutical companies, and trial registries. We imposed no language restrictions, and the search was updated until Jan 8, 2016. Doses of SSRIs were converted to fluoxetine equivalents. Trials of antidepressants for patients with depression and a serious concomitant physical illness were excluded. The main outcomes were efficacy (treatment response defined as 50% or greater reduction in depression severity), tolerability (dropouts due to adverse effects), and acceptability (dropouts for any reasons), all after a median of 8 weeks of treatment (range 4–12 weeks). We used a random-effects, dose-response meta-analysis model with flexible splines for SSRIs, venlafaxine, and mirtazapine. Findings 28 554 records were identified through our search (24 524 published and 4030 unpublished records). 561 published and 121 unpublished full-text records were assessed for eligibility, and 77 studies were included (19 364 participants; mean age 42·5 years, SD 11·0; 7156 [60·9%] of 11 749 reported were women). For SSRIs (99 treatment groups), the dose-efficacy curve showed a gradual increase up to doses between 20 mg and 40 mg fluoxetine equivalents, and a flat to decreasing trend through the higher licensed doses up to 80 mg fluoxetine equivalents. Dropouts due to adverse effects increased steeply through the examined range. The relationship between the dose and dropouts for any reason indicated optimal acceptability for the SSRIs in the lower licensed range between 20 mg and 40 mg fluoxetine equivalents. Venlafaxine (16 treatment groups) had an initially increasing dose-efficacy relationship up to around 75–150 mg, followed by a more modest increase, whereas for mirtazapine (11 treatment groups) efficacy increased up to a dose of about 30 mg and then decreased. Both venlafaxine and mirtazapine showed optimal acceptability in the lower range of their licensed dose. These results were robust to several sensitivity analyses. Interpretation For the most commonly used second-generation antidepressants, the lower range of the licensed dose achieves the optimal balance between efficacy, tolerability, and acceptability in the acute treatment of major depression. Funding Japan Society for the Promotion of Science, Swiss National Science Foundation, and National Institute for Health Research.

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Safety of 80 antidepressants, antipsychotics, anti‐attention‐deficit/hyperactivity medications and mood stabilizers in children and adolescents with psychiatric disorders: a large scale systematic meta‐review of 78 adverse effects

Marco Solmi, Michele Fornaro, Edoardo Ostinelli … (2020)

Mental disorders frequently begin in childhood or adolescence. Psychotropic medications have various indications for the treatment of mental disorders in this age group and are used not infrequently off‐label. However, the adverse effects of these medications require special attention during developmentally sensitive periods of life. For this meta‐review, we systematically searched network meta‐analyses and meta‐analyses of randomized controlled trials (RCTs), individual RCTs, and cohort studies reporting on 78 a priori selected adverse events across 19 categories of 80 psychotropic medications – including antidepressants, antipsychotics, anti‐attention‐deficit/hyperactivity disorder (ADHD) medications and mood stabilizers – in children and adolescents with mental disorders. We included data from nine network meta‐analyses, 39 meta‐analyses, 90 individual RCTs, and eight cohort studies, including 337,686 children and adolescents. Data on ≥20% of the 78 adverse events were available for six antidepressants (sertraline, escitalopram, paroxetine, fluoxetine, venlafaxine and vilazodone), eight antipsychotics (risperidone, quetiapine, aripiprazole, lurasidone, paliperidone, ziprasidone, olanzapine and asenapine), three anti‐ADHD medications (methylphenidate, atomoxetine and guanfacine), and two mood stabilizers (valproate and lithium). Among these medications with data on ≥20% of the 78 adverse events, a safer profile emerged for escitalopram and fluoxetine among antidepressants, lurasidone for antipsychotics, methylphenidate among anti‐ADHD medications, and lithium among mood stabilizers. The available literature raised most concerns about the safety of venlafaxine, olanzapine, atomoxetine, guanfacine and valproate. Nausea/vomiting and discontinuation due to adverse event were most frequently associated with antidepressants; sedation, extrapyramidal side effects, and weight gain with antipsychotics; anorexia and insomnia with anti‐ADHD medications; sedation and weight gain with mood stabilizers. The results of this comprehensive and updated quantitative systematic meta‐review of top‐tier evidence regarding the safety of antidepressants, antipsychotics, anti‐ADHD medications and mood stabilizers in children and adolescents can inform clinical practice, research and treatment guidelines.

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Author and article information

Journal

Journal ID (nlm-ta): Ther Clin Risk Manag

Journal ID (iso-abbrev): Ther Clin Risk Manag

Journal ID (publisher-id): tcrm

Title: Therapeutics and Clinical Risk Management

Publisher: Dove

ISSN (Print): 1176-6336

ISSN (Electronic): 1178-203X

Publication date (Electronic): 13 August 2022

Publication date Collection: 2022

Volume: 18

Pages: 799-812

Affiliations

[1 ]Psychosomatic Medicine Research Division, Inner Mongolia Medical University , Huhhot, People’s Republic of China

[2 ]Beijing Hui-Long-Guan Hospital, Peking University , Beijing, People’s Republic of China

[3 ]Department of Biomedical Engineering, College of Future Technology, Peking University , Beijing, People’s Republic of China

[4 ]Xinjiang Key Laboratory of Neurological Disorder Research, The Second Affiliated Hospital of Xinjiang Medical University , Urumqi, People’s Republic of China

[5 ]School of Mental Health, Wenzhou Medical University , Wenzhou, People’s Republic of China

[6 ]Department of Anesthesiology, The Second Affiliated Hospital of Xiamen Medical College , Xiamen, People’s Republic of China

Author notes

Correspondence: Fan Wang, Beijing Hui-Long-Guan Hospital, Peking University , Beijing, 100096, People’s Republic of China, Tel +86 10 83024429, Fax +86 10 62716285, Email FanWang@bjmu.edu.cn

[*]

These authors contributed equally to this work

Author information

Fan Wang http://orcid.org/0000-0002-7048-8166

Article

Publisher ID: 363404

DOI: 10.2147/TCRM.S363404

PMC ID: 9386738

PubMed ID: 35992228

SO-VID: 9fff23c3-9cde-4743-abff-624da81f6bd9

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This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms ( https://www.dovepress.com/terms.php).

History

Date received : 01 March 2022

Date accepted : 29 July 2022

Page count

Figures: 8, Tables: 7, References: 67, Pages: 14

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Risks of Digestive System Side-Effects of Selective Serotonin Reuptake Inhibitors in Patients with Depression: A Network Meta-Analysis

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Most cited references 67

Differential effects of psychotropic drugs on microbiome composition and gastrointestinal function

Optimal dose of selective serotonin reuptake inhibitors, venlafaxine, and mirtazapine in major depression: a systematic review and dose-response meta-analysis

Safety of 80 antidepressants, antipsychotics, anti‐attention‐deficit/hyperactivity medications and mood stabilizers in children and adolescents with psychiatric disorders: a large scale systematic meta‐review of 78 adverse effects

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