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Incidence of adverse events and comparative tolerability of selective serotonin reuptake inhibitors, and serotonin and norepinephrine reuptake inhibitors for the treatment of anxiety, obsessive-compulsive, and stress disorders: a systematic review and network meta-analysis
Open accessAbstract
Selective serotonin reuptake inhibitors (SSRIs) and serotonin and norepinephrine reuptake inhibitors (SNRIs) show similar efficacy as treatments for anxiety, obsessive-compulsive, and stress-related disorders. Hence, comparisons of adverse event rates across medications are an essential component of clinical decision-making. We aimed to compare patterns of adverse events associated with SSRIs and SNRIs in the treatment of children and adults diagnosed with these disorders through a network meta-analysis. We searched MEDLINE, PsycINFO, Embase, Cochrane, websites of regulatory agencies, and international registers from inception to 09 September 2022, for randomized controlled trials assessing the efficacy of SSRIs or SNRIs. We analyzed the proportion of participants experiencing at least one adverse event and incidence rates of 17 specific adverse events. We estimated incidence rates and odds ratios through network meta-analysis with random effects and three-level models. We analyzed 799 outcome measures from 80 studies (n = 21 338). Participants in medication groups presented higher rates of adverse events (80.22%, 95% CI 76.13–83.76) when compared to placebo groups (71.21%, 67.00–75.09). Nausea was the most common adverse event (25.71%, CI 23.96–27.54), while weight change was the least common (3.56%, 1.68–7.37). We found higher rates of adverse events of medications over placebo for most medications, except sertraline and fluoxetine. We found significant differences between medications for overall tolerability and for autonomic, gastrointestinal, and sleep-related symptoms. Adverse events are a common reason that patients discontinue SSRIs and SNRIs. Results presented here guide clinical decision-making when clinicians weigh one medication over another. This might improve treatment acceptability and compliance.
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Stefánsdóttir et al. meta-analysis found both SSRIs and SNRIs are effective treatments for pediatric samples diagnosed with anxiety disorders.
“The authors found that both SSRIs and SNRIs are effective treatments for this age group and diagnosis.”
From The risks versus the benefits of pharmacological intervention in social anxiety disorder in children (2025) · cites this paper as [45]
The Abstract says SSRIs and SNRIs have similar efficacy for anxiety and related disorders, and the Results include trials involving children and adolescents. But this paper’s own findings concern adverse events; it does not report that both drug classes are effective specifically for pediatric anxiety. The attributed author name also differs from the cited paper’s authors, Gosmann et al. (LLM, conf=0.84)
Experimental — accuracy not yet measuredIn sum, review suggests despite efficacy of SSRIs for pediatric SAD, psychotherapy alone or in combination with pharmacological treatment is preferred because it poses less risk of adverse effects and dropout.
“In sum, our review of the literature suggests that despite the efficacy of SSRIs for pediatric SAD, psychotherapy alone or in combination with pharmacological treatment is the preferred treatment approach because it poses less risk of causing adverse effects and dropout [35,45].”
From The risks versus the benefits of pharmacological intervention in social anxiety disorder in children (2025) · cites this paper as [45]
The Results report that medications were less tolerated than placebo for most specific adverse events, supporting the concern about medication-related adverse effects. But the Inclusion criteria exclude combined medication-and-psychotherapy treatment arms, and the paper does not compare psychotherapy with medication or establish lower dropout with psychotherapy in pediatric social anxiety disorder. The preference for psychotherapy is therefore not supported by this source. (LLM, conf=0.87)
Experimental — accuracy not yet measuredThe literature suggests that such interventions may lead to increased hyperactivity, irritability, impulsivity, and hostile behavior.
“The literature suggests that such interventions may lead to increased hyperactivity, irritability, impulsivity, and hostile behavior [45,76].”
From The risks versus the benefits of pharmacological intervention in social anxiety disorder in children (2025) · cites this paper as [45]
The Data extraction and data synthesis section lists agitation as an adverse event, and the table in the Discussion reports a higher incidence with medication than with placebo. Agitation is related to the behavioral effects claimed, but our copy does not report increased hyperactivity, irritability, impulsivity, or hostile behavior specifically. (LLM, conf=0.78)
Experimental — accuracy not yet measuredOther reported physical effects of pharmacotherapy include gastrointestinal discomfort, such as abdominal pain or nausea, as well as sleep disturbances.
“Other reported physical effects include gastrointestinal discomfort, such as abdominal pain or nausea, as well as sleep disturbances [45,76,78].”
From The risks versus the benefits of pharmacological intervention in social anxiety disorder in children (2025) · cites this paper as [45]
The Data extraction and data synthesis section lists nausea among gastrointestinal adverse events and insomnia and somnolence among sleep-related adverse events; the Discussion also identifies these as common symptoms associated with SSRIs and SNRIs. The paper does not specifically report abdominal pain, so that example is not supported by our copy. (LLM, conf=0.85)
Experimental — accuracy not yet measuredPharmacological intervention can induce significant behavioral changes in children, impacting their daily behavior and social interactions.
“Beyond the psychological effects, pharmacological intervention can also induce significant behavioral changes in children, impacting their daily behavior and social interactions [45].”
From The risks versus the benefits of pharmacological intervention in social anxiety disorder in children (2025) · cites this paper as [45]
Table 2 (reproduced in the Discussion; page not available) reports more agitation with SSRIs and SNRIs than with placebo, providing some support for a medication-related behavioral effect. The paper includes trials involving children and adolescents, but this agitation estimate is not child-specific, and the copy does not report effects on children's daily behavior or social interactions. (LLM, conf=0.79)
Experimental — accuracy not yet measured
Treatments with SSRIs and SNRIs have raised significant concerns regarding potential side effects.
“Treatments with SSRIs and SNRIs have also raised significant concerns regarding potential side effects [45].”
From The risks versus the benefits of pharmacological intervention in social anxiety disorder in children (2025) · cites this paper as [45]
Stefánsdóttir et al. suggests SSRIs and SNRIs treatments do not increase the risk of attrition when compared to placebo.
“Moreover, this study suggests that SSRIs and SNRIs treatments do not increase the risk of attrition when compared to placebo.”
From The risks versus the benefits of pharmacological intervention in social anxiety disorder in children (2025) · cites this paper as [45]
The Data extraction and data synthesis section lists adverse-event and suicide outcomes, but not attrition. The Results compare adverse-event rates between medication and placebo groups; they do not compare dropout or discontinuation rates. Searches for attrition, dropout, and discontinuation found no passage establishing the claimed comparison. (LLM, conf=0.76)
Experimental — accuracy not yet measuredPharmacological treatments displayed higher rates of attrition than psychotherapy, specifically with pediatric samples.
“Nevertheless, it is important to note that pharmacological treatments displayed higher rates of attrition than psychotherapy, specifically with pediatric samples.”
From The risks versus the benefits of pharmacological intervention in social anxiety disorder in children (2025) · cites this paper as [45]
The Inclusion criteria (page unavailable) specify comparisons among medications and placebo and exclude combined medication–psychotherapy arms. The Results report adverse-event rates, not attrition rates. Searches for attrition, dropout, and psychotherapy found no pediatric comparison of pharmacological treatment with psychotherapy in our copy. (LLM, conf=0.78)
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Metadata
- Authors
- Gosmann, N. P., Costa, M. D. A., Jaeger, M. D. B., Frozi, J., Spanemberg, L., Manfro, G. G., Cortese, S., Cuijpers, P., Pine, D. S., & Salum, G. A.
- Affiliations
- Universidade Federal do Rio Grande do Sul (BR)
- Pontifícia Universidade Católica do Rio Grande do Sul (BR)
- University of Southampton (GB)
- Amsterdam Public Health (NL)
- National Institutes of Health (US)
- Corresponding author
- Gosmann, Natan Pereira
- ORCID
- Venue
- Psychological Medicine
- Publisher
- Cambridge University Press (CUP)
- Published
- 2023-06-06
- Volume
- 53
- Issue
- 9
- Pages
- 3783-3792
- ISSN
- 0033-2917 (ISSN-L)
- 1469-8978
- OpenAlex
- W4379509189
- Cited by
- 28
- References
- 42
- Citations by year
- 2026: 12 · 2025: 8 · 2024: 8
- FWCI
- 1.18
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Psychological Medicine (publishedVersion)
- PubMed (publishedVersion)
- VU Research Portal (publishedVersion, other-oa)
- ePrints Soton (University of Southampton) (acceptedVersion)
- Funders
- Conselho Nacional de Desenvolvimento Científico e Tecnológico (001)
- Associação Fundo de Incentivo à Pesquisa (001)
- Child Mind Institute (001)
- Topics
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Anxiety, Depression, Psychometrics, Treatment, Cognitive Processes
- Health Sciences › Medicine › Pharmacology (medical) › Treatment of Major Depression
- Health Sciences › Medicine › Psychiatry and Mental health › Mental Health Treatment and Access
- Keywords
- selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, adverse events, drug tolerability, anxiety disorders, obsessive-compulsive disorder, stress-related disorders, nausea, weight change, sertraline, fluoxetine, drug discontinuation, autonomic symptoms
- MeSH terms
- Serotonin and Noradrenaline Reuptake Inhibitors, Network Meta-Analysis, Adult, Anxiety, Child, Humans, Norepinephrine, Obsessive-Compulsive Disorder, Serotonin, Incidence, Selective Serotonin Reuptake Inhibitors
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Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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