Front. PsychiatryFrontiers in PsychiatryFront. Psychiatry1664-0640Frontiers Media S.A.10.3389/fpsyt.2026.1769044Systematic ReviewThe association of statin use with the risk of anxiety: a systematic review and meta-analysisYanYutong1†Project administrationFunding acquisitionValidationWriting – original draftSupervisionFormal analysisWriting – review & editingData curationSoftwareInvestigationConceptualizationResourcesVisualizationMethodologyDengSijing1†SoftwareFunding acquisitionWriting – review & editingWriting – original draftResourcesFormal analysisVisualizationData curationMethodologyInvestigationSupervisionConceptualizationValidationProject administrationLiYing2†MethodologyWriting – original draftSoftwareVisualizationInvestigationValidationFunding acquisitionConceptualizationData curationProject administrationResourcesSupervisionWriting – review & editingFormal analysisFuJie2SupervisionWriting – review & editingFunding acquisitionWriting – original draftResourcesInvestigationData curationSoftwareProject administrationFormal analysisConceptualizationValidationMethodologyVisualizationGongHongxia2Project administrationSupervisionWriting – review & editingMethodologyFormal analysisVisualizationInvestigationSoftwareResourcesData curationConceptualizationWriting – original draftFunding acquisitionValidationZhangHaiyan2*ValidationFormal analysisSupervisionData curationConceptualizationWriting – review & editingMethodologyProject administrationInvestigationWriting – original draftSoftwareResourcesFunding acquisitionVisualizationZhangFeng2*SoftwareWriting – original draftInvestigationResourcesWriting – review & editingFunding acquisitionMethodologyValidationFormal analysisProject administrationVisualizationSupervisionData curationConceptualizationSchool of Health and Wellbeing, University of Glasgow, Glasgow, United KingdomDepartment of Cardiology, Daping Hospital, Army Medical University, Chongqing, ChinaCorrespondence: Haiyan Zhang, zhy123@tmmu.edu.cn; Feng Zhang, zf1988@tmmu.edu.cn
Statins are widely prescribed for the primary and secondary prevention of cardiovascular diseases, given their efficacy in lowering low-density lipoprotein cholesterol levels and reducing the risk of cardiovascular events. However, statins may exert effects on the central nervous system. Previous studies have hypothesized that statin use may exert protective effects against anxiety via mechanisms including anti-inflammatory activity and improved endothelial function. Conversely, observational studies have also reported associations between statin use and increased anxiety symptoms. To date, findings on the association between statin use and anxiety risk have been inconsistent. Therefore, this systematic review and meta-analysis aimed to systematically search and assess the available evidence, clarify the association between statin use and the risk of anxiety, and offer evidence-based guidance for clinical practice.
Methods
We searched PubMed, Web of Science, Embase, and the Cochrane Library for studies investigating the association between statin use and anxiety risk, with the search period ranging from the inception of each database to January 2026. Studies were screened against predefined inclusion criteria, and relevant data were extracted. The Risk of Bias in Non-randomized Studies of Interventions (ROBINS-I) tool was employed to assess the risk of bias in included non-randomized studies. Hazard ratios (HRs) and 95% confidence intervals (CIs) were pooled with a random-effects model.
Results
A total of five studies with 1,919,059 participants were included. The meta-analysis showed that statin use was not associated with an increased risk of anxiety disorders (HR = 0.75,95% CI (0.55,1.04), P = 0.08). Subgroup analyses revealed that statin use was associated with a reduced risk of anxiety only in studies with a sample size < 10,000 (P < 0.05). No significant association was observed in other subgroups, including those stratified by region or study design, notably, studies with a sample size > 10,000 also showed no significant effect (P > 0.05).
Conclusion
The existing evidence suggests that statin use may not be associated with the risk of developing anxiety. Given the limitations of this study, future large-scale, multi-center, and prospective cohort studies are warranted to validate these findings.
anxietyanxiety disordersmeta-analysisstatinssystematic reviewThe author(s) declared that financial support was not received for this work and/or its publication.section-at-acceptanceAnxiety and Stress DisordersIntroduction
Anxiety disorders represent a prevalent category of mental illnesses (1), characterized by excessive worry, fear and tension that severely impair patients’ daily functioning and social interactions (2). Large-scale epidemiological studies have shown that anxiety disorders severely impair patients’ daily functioning and social interactions at some point in their lives (3). Currently, approximately 301 million people worldwide suffer from anxiety disorders, making it the second most common mental disorder after depression (4). Compared with the general population, individuals with anxiety disorders face a substantially higher risk of mortality from both natural and unnatural causes (5). Consequently, anxiety disorders have imposed an economic burden and social pressure on numerous countries and regions (6–8). Despite the diverse clinical manifestations of anxiety disorders, their diagnosis and treatment are hindered by an incomplete understanding of their etiologies and pathological mechanisms.
Statins are among the most widely prescribed medications globally, utilized for the primary and secondary prevention of cardiovascular events (9). However, their potential neuropsychiatric side effects, particularly the association with anxiety risk, remain controversial (10, 11). On the one hand, statins are hypothesized to exert neuroprotective effects and may reduce anxiety risk via mechanisms such as anti-inflammatory activity, antioxidative effects, and modulation of neurotransmitter systems (12, 13). On the other hand, observational studies have suggested that statin use may be associated with exacerbated anxiety symptoms, possibly mediated by interference with cholesterol metabolism and neurotransmitter systems (14–17).
Although previous meta-analyses have explored the association between statins and anxiety, suggesting a potential anxiety-reducing effect (18), recent large-scale cohort studies and updated analyses have reported no significant associations (19–21). This inconsistency not only exists among observational studies but also extends to higher-level evidence syntheses, leading to ambiguity in clinical decision-making. Previous meta-analyses examining the statin-anxiety association included only two studies, which may have had limited statistical power. Methodologically, these studies failed to adopt the currently recommended ROBINS-I tool for rigorous bias assessment of observational studies. To address these gaps in evidence and methodology, the present study conducted an updated systematic review and meta-analysis incorporating the latest literature. This study aimed to comprehensively search and evaluate existing evidence, clarify the association between statin use and anxiety risk, and provide evidence-based guidance for clinical medication decisions.
Methods
This meta-analysis was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines (22–24). The study protocol was retrospectively registered in PROSPERO (Registration number: CRD420261291901).
Search strategy
A systematic literature search was performed in PubMed, Web of Science, Embase, and the Cochrane Library. The search period covered all publications from the establishment of each database up to January 2026, with no language restrictions. Additionally, reference lists of included studies and relevant systematic reviews were manually searched to identify additional eligible publications. Search terms related to statins and anxiety risk included: statin, statins, atorvastatin, simvastatin, anxiety, anxiety disorders, risk, incidence, association, etc. Taking PubMed as an example, we elaborately listed the search terms for the association between statins and the risk of anxiety, and performed the retrieval with Boolean logic operators. The detailed search strategy is provided in the supplementary material (Supplementary Table S1).
Inclusion and exclusion criteria
Inclusion criteria:
(1) Observational study design (cross-sectional, case-control, or cohort study);
(2) Comparison between participants receiving statin therapy (experimental group) and those not receiving statin therapy (control group);
(3) Anxiety defined using standardized questionnaires (e.g., Generalized Anxiety Disorder-7 Scale [GAD-7], Hospital Anxiety and Depression Scale-Anxiety Subscale [HADS-A], State-Trait Anxiety Inventory [STAI]) or medical record-derived diagnostic codes/anti-anxiety medication prescriptions (e.g., selective serotonin reuptake inhibitors, benzodiazepines);
(4) Provision of effect sizes (e.g., HR, odds ratio) with 95% CIs.
Exclusion criteria:
(1) Insufficient or invalid data provided;
(2) Case report, comments, reviews, systematic review.
(3) Duplicate publications.
Data extraction
Two independent reviewers screened the studies, extracted data, and cross-validated the results. Disagreements were resolved through discussion and consensus. Extracted data included: author names and publication year, country of origin, study design, sample size, age, gender distribution, anxiety assessment tools, follow-up duration, adjustment factors, and effect sizes.
Risk of bias assessment
The ROBINS-I tool was used to assess the risk of bias in included non-randomized intervention studies. Each study was evaluated across seven domains: confounding, selection of participants, classification of interventions, deviations from intended interventions, missing data, measurement of outcomes, and selection of reported results. The overall risk of bias for each study was determined based on the highest bias level identified across these domains and classified as low, moderate, or high according to established criteria. Two independent researchers conducted the assessments, with disagreements resolved through discussion.
Statistical analysis
Statistical analysis was performed using RevMan 5.3. HRs and its 95% CI were used as effect measures to evaluate the association between the statin use and the anxiety risk. Heterogeneity among the studies was assessed using the χ2 test and I2. If P > 0.10 and I2 < 50%, heterogeneity was considered acceptable, and a fixed-effects model was used for analysis. If P ≤ 0.10 and I2 ≥ 50%, significant heterogeneity was assumed, and a random-effects model was employed. Subgroup analyses were conducted based on region (Asian vs Non-Asian), study design (Retrospective vs Prospective), and sample size (<10,000 vs >10,000). Sensitivity analyses were performed by changing the effect model and excluding studies with high risk of bias to assess the stability of the results. Funnel plot analysis for publication bias was planned if ≥ 10 studies were included.
ResultsLiterature search
The initial database search yielded 462 articles. After rigorous screening, five literatures were finally included for a meta-analysis (Figure 1).
Flow chart of article selection process.
PRISMA flow diagram illustrating the systematic review process: four stages are labeled identification, screening, eligibility, and included. Four hundred sixty-two records were identified, three hundred eight screened, fifteen full texts assessed, and five studies included in synthesis and meta-analysis.Study characteristics
The five included studies involved a total of 1,919,059 participants. Two studies adopted a prospective design, and three were retrospective design. Two studies were conducted in China, while the remaining ones were carried out in the UK, the US, and Sweden. The sample sizes of these studies ranged from 371 to 1,149,384. Detailed characteristics of the included studies are summarized in Table 1. Risk of bias assessment using the ROBINS-I tool revealed that four studies had a moderate overall risk of bias, and one study had a high risk of bias (Table 2).
Characteristics of included studies.
References
Study design
Data source
Country
Sample size
Age(median/mean)
Male sex (%)
Anxiety outcome
Follow-up period
Adjustment factors
Molero et al. (19)
Retrospective cohort study
Swedish nationwide registers
Swedish
1,149,384
Not report
625,616 (54.4%)
F40–F45, F48
8 Years
1. Demographic statistics and socio-economic factors: Age
Yang et al. (20)
Prospective cohort study
UK Biobank
UK
363,551
56.73
173,016(47.6%)
F40-F41,Generalized Anxiety Disorder
13 Years
1. Demographic statistics and socio-economic factors: Age, Sex, Education, Ethnicity, Townsend Deprivation Index, Average Household Income.2. Lifestyle and behavioral factors: Body Mass Index, Smoking Status, Drinking Status, Physical Activity.3. Dietary factors: Fruit Intake, Vegetable Intake, Fish Intake, Red Meat Intake, Processed Meat Intake, Whole Grains, Dairy Products.4. Clinical diseases and historical factors: Diabetes, High Blood Pressure, Heart Problem, Cerebrovascular Disease, Dyslipidemia, Cancer, Chronic Lung Disease, Other Psychiatric Disorders, Family History of Depression.5. Drug combination factors: Antihistamines, Beta Blockers, Nonsteroidal Anti-inflammatory Drugs,Acetaminophen, Opioids, Systemic Glucocorticoids, Psychotropic Medications.
Ye et al. (21)
Case-control study
Hong Kong Clinical Data Analysis & Reporting System
China
396,614
58.43
205,625 (51.85%)
ICD-9-CM
10 Years
Not report
Yeh et al. (25)
Retrospective cohort study
Taiwan’s National Health Insurance Research Database
China
9,139
65.1
5,630(61.60%)
ICD-9-CM
The mean follow-up durations were 7.74 and 5.09 years for the statin and nonstatin users
1. Demographic statistics and socio-economic factors: Age, Gender, Education.2. Study Design and Follow-up Factors: Length of Follow-up, Statin Usage Prior to Study Entry.3. Physiological and biochemical indicators: Blood Glucose Level, Systolic Blood Pressure, Diastolic Blood Pressure, Total Cholesterol, High-density Lipoprotein, Heart Rate.4. Lifestyle and behavioral factors: Current Smoking, Regular Exercise, Alcohol Use.5. Psychosocial factors: Past Major Life Events, Anticipated Major Future Life Events.6. Drug combination factors: Use of Antidepressants at Time of Enrollment, Use of Anti-anxiety Drugs at Time of Enrollment, Use of Beta-blockers at Enrollment and During Follow-up, Use of Calcium Channel Blockers at Enrollment and During Follow-up.7. Clinical diseases and historical factors: History of Catheterization, History of Myocardial Infarction, History of Hypertension, History of Diabetes, Incidence of Myocardial Infarction During Follow-up, Incidence of Stroke During Follow-up, Incidence of Catheterization During Follow-up, Incidence of Revascularization During Follow-up.
Summary of bias assessment using the ROBINS-I tool.
References
D1
D2
D3
D4
D5
D6
D7
Overall bias
Molero et al. (19)
Low
Low
Low
Low
Low
Moderate
Low
Moderate
Yang et al. (20)
Low
Low
Low
Low
Low
Low
Moderate
Moderate
Ye et al. (21)
High
Low
Low
Low
Low
Low
Low
High
Yeh et al. (25)
Low
Moderate
Low
Low
Moderate
Moderate
Low
Moderate
Young-Xu et al. (26)
Moderate
Low
Low
Low
Low
Low
Low
Moderate
Domains:
D1: Bias due to confounding.
D2: Bias in selection of participants.
D3: Bias in classification of exposures.
D4: Bias due to deviations from intended exposures.
D5: Bias due to missing data.
D6: Bias in measurement of outcomes.
D7: Bias in selection of the reported result.
Red indicates high risk, green indicates low risk, and light yellow indicates moderate risk.
Main analysis
Heterogeneity testing indicated significant heterogeneity among the included studies (P < 0.00001, I2 = 96%), so a random-effects model was used for pooling. The meta-analysis showed that statin use was not associated with an increased risk of anxiety disorders (HR = 0.75, 95% CI (0.55,1.04), P = 0.08) (Figure 2).
Forest plot of the association between statin use and anxiety risk. Red indicates high risk, green indicates low risk, and light yellow indicates moderate risk.
Forest plot displaying hazard ratios and confidence intervals from five studies, with a pooled hazard ratio of 0.75 and high heterogeneity. Risk of bias assessment uses colored circles, with green for low, yellow for unclear, and red for high bias, across seven bias criteria explained in a detailed legend.Subgroup analysis
Subgroup analysis based on region (Asian vs. Non-Asian), study design (retrospective vs. prospective), and sample size (<10,000 vs >10,000) are presented in Table 3. Statin use was associated with a reduced anxiety risk only in studies with a sample size < 10,000 (P < 0.05). No significant associations were observed in subgroups stratified by region (Asian vs. Non-Asian), study design (retrospective vs. prospective), or sample size > 10,000 (P > 0.05).
Subgroup analysis.
Subgroup analysis
No. of studies
Heterogeneity
HR(95%CI)
P value
I2
P
Study design
Retrospective
3
98.00%
< 0.00001
0.71(0.43,1.15)
0.165
Prospective
2
63.20%
< 0.00001
0.85(0.63,1.16)
0.319
Sample size
<10000
2
90.70%
0.001
0.48(0.24,0.95)
0.036
>10000
3
0.00%
0.760
0.99(0.94,1.05)
0.817
Region
Asian
2
98.90%
< 0.00001
0.59(0.20,1.73)
0.338
Non-Asian
3
41.60%
0.181
0.97(0.90,1.04)
0.356
The bold font indicates statistically significant differences.
Sensitivity analysis
Sensitivity analyses by changing the effect model showed that under the fixed-effects model, statin use was associated with a reduced risk of anxiety (Figure 3). After excluding the study by Ye et al., the results indicated no significant association between statin use and anxiety risk (HR = 0.69,95% CI (0.44,1.08), P = 0.11), suggesting instability of the meta-analysis results.
Forest plot for sensitivity analysis using the fixed-effects model. Red indicates high risk, green indicates low risk, and light yellow indicates moderate risk.
Forest plot displaying hazard ratios with 95 percent confidence intervals for five studies, summary statistics for heterogeneity, overall effect test, and a color-coded risk of bias assessment matrix across seven domains per study.Publication Bias
Given the small number of included studies (n = 5), funnel plot analysis for publication bias was not feasible.
Discussion
This systematic review and meta-analysis synthesized data from five studies involving nearly 2 million participants, revealing no significant association between statin use and anxiety risk. This finding contradicts the hypothesis that “statins may reduce anxiety” proposed by some previous observational studies (25, 26) but is consistent with the results of most high-quality cohort studies, including a Swedish total-population cohort study that also reported no significant association between statin use and anxiety risk (19, 20). Furthermore, a recent meta-analysis on depression and inflammation also indicated that statin use for improving depressive symptoms did not increase anxiety risk (14).
In the present study, the pooled HR point estimate leaned toward a protective effect (HR < 1) but did not reach statistical significance, indicating that existing evidence is insufficient to confirm whether statins exert significant protective or harmful effects on anxiety. The meta-analysis showed substantial heterogeneity, and sensitivity analyses revealed that statin use might reduce the risk of anxiety under the fixed-effects model. This uncertainty may arise from heterogeneity in population characteristics, statin types and doses, anxiety assessment methods, and follow-up durations across studies. Evidence on the impact of statin use on the pathogenesis of mood disorders remains inconsistent: some studies report associations between statin use and mood disorders, while others suggest beneficial effects on mental health (14). A systematic meta-analysis of randomized, double-blind, placebo-controlled trials indicated that adjunctive statin therapy may be beneficial for treating depressive symptoms (27). Another study showed that statin use could reduce the risk of depression and anxiety in patients with coronary artery disease (26). Statins are potent cholesterol-lowering agents that also inhibit endotoxin-induced inflammatory responses and reduce lipopolysaccharide-induced monocyte cytokine production (28). Therefore, their anti-inflammatory and antioxidant properties may contribute to the treatment of depression and improving mood (29). A systematic review and meta-analysis on the impact of statins on mental health provided partial support for the emotional benefits of these drugs (18). A retrospective cohort study investigated the effect of statins on anxiety and major depression in patients with asthma-chronic obstructive pulmonary disease overlap syndrome found that statin use significantly reduced the risk of anxiety and major depression (25).
Subgroup analyses revealed a statistically significant reduction in the risk of anxiety only in small-sample studies (< 10,000 participants), which may explain the conflicting results in the previous literature. Notably, the two small-sample studies included in this meta-analysis were rated as having a moderate risk of bias, while among the three large-sample studies, one had a high risk of bias. This suggests that studies reporting “protective effects” may be more susceptible to methodological limitations. Small-sample studies may have greater variability or limitations in population selection, control of confounding factors (e.g., severity of cardiovascular disease, comorbid psychiatric history), or outcome assessment. These biases may systematically underestimate risks or overestimate protective effects. The smallest study (26) (26), despite extensive adjustments, was limited to a specific population from a single cardiovascular center, restricting generalizability. In contrast, the largest study with a relatively low risk of bias (19) (19) provided an estimate closer to a null effect, which may better reflect the true association in the general population after adequate confounding control. Therefore, inconsistencies in previous observational studies may partly be attributed to differences in study size and methodological quality. This emphasizes the need for caution when interpreting observational evidence in this field and prioritizing data from large-scale, high-quality studies. Furthermore, variations in anxiety assessment methods across studies may have influenced the results: some studies (19, 21, 25) relied on medical diagnostic codes (more likely to identify clinically significant anxiety disorders), while others (20, 26)used standardized anxiety symptom scales (more sensitive to subclinical or mild symptoms). Unfortunately, due to the limited number of eligible studies, subgroup analysis based on assessment methods was not feasible to examine this potential impact. Future studies should detail anxiety assessment tools and definitions to facilitate more refined comparisons and syntheses.
Animal studies have provided insights into the potential anti-anxiety mechanisms of statins. A study evaluating the effects of different statins in a Wistar rat anxiety model showed that atorvastatin, rosuvastatin, and simvastatin all exerted significant anti-anxiety effects compared with the control group (30). Santos et al. (31) reported that treatment with simvastatin and/or fluoxetine alleviated anxiety-like behaviors in adult rats in the elevated plus maze and open field tests. Statins may alleviate anxiety symptoms through multiple mechanisms: inhibiting pro-inflammatory factors, regulating serotonin and neurotransmitter metabolism, improving cerebral blood flow and endothelial function, and upregulating neuroprotective factors. Inflammation is recognized as a key pathophysiological basis for mood disorders such as anxiety and depression (32). Anxiety is often accompanied by activation of the inflammatory response, and elevated levels of inflammatory factors (e.g., tumor necrosis factor-α, interleukin-6) may affect neurotransmitter metabolism and neuroplasticity, thereby exacerbating anxiety (32). Statins may reduce chronic inflammation-induced or -exacerbated anxiety by inhibiting multiple pro-inflammatory cytokines (33). Cholesterol is an important precursor for neurotransmitter synthesis (e.g., serotonin, dopamine). While statins lower cholesterol levels, they may also modulate neurotransmitter synthesis and metabolism.
Studies have shown that statins may increase cerebral serotonin concentrations by regulating serotonin transporter function, exerting anti-anxiety effects (34). Additionally, statins may upregulate N-methyl-D-aspartate receptors to improve emotional behavior (13). Statins can improve vascular endothelial function, increase cerebral blood perfusion, and provide sufficient oxygen and nutrients to the brain, supporting normal neural cell function (35). Furthermore, statins may promote neural cell repair and regeneration by regulating the expression of neuroprotective factors such as brain-derived neurotrophic factor, exerting positive effects on anxiety-related neural circuit function (36).
Despite these potential mechanisms, the link between biological plausibility and clinical observations must be interpreted with caution. Existing evidence does not indicate that statins increase anxiety risk, so statin therapy should not be avoided or delayed due to concerns about inducing anxiety. The established benefits of statins in the primary and secondary prevention of cardiovascular diseases should be the primary consideration in clinical decision-making. For patients with anxiety disorders or anxiety proneness who require statin therapy, clinicians should inform them of the current evidence to alleviate unnecessary concerns. Routine monitoring of emotional status during treatment is a reasonable clinical practice. If patients report new or exacerbated anxiety symptoms, a comprehensive assessment should be conducted to consider multiple potential causes (e.g., underlying diseases, other medications, life stressors) rather than presuming statins as the cause.
Limitations
This study has several limitations. First, limited data on specific statin types (e.g., atorvastatin, simvastatin), doses, treatment durations, and medication adherence precluded in-depth analyses of these factors, limiting the precision of the conclusions. Differences in the pharmacokinetic properties of statins (e.g., lipophilicity, blood-brain barrier permeability, anti-inflammatory potency) may affect cholesterol metabolism, inflammatory responses, and neurotransmitter function in the central nervous system, resulting in varying effects on anxiety risk. Additionally, differences in doses and treatment durations may result in varying cumulative or threshold effects, which are potential sources of heterogeneity in observational studies and the present meta-analysis. Future studies should conduct well-designed, large-scale prospective cohort studies and systematically collect and report detailed statin treatment information. Secondly, although most studies adjusted for key confounding factors, inconsistencies in covariate adjustment across studies cannot fully exclude residual confounding. Thirdly, the meta-analysis exhibited high heterogeneity. Although subgroup and sensitivity analyses were conducted to explore and control for heterogeneity, the complex and diverse sources of heterogeneity (e.g., differences in baseline cardiovascular disease comorbidity across study populations) rendered complete elimination difficult. A neglected core potential source lies in discrepancies in the baseline health status of the study populations, particularly with respect to the comorbidity profile of cardiovascular disease (CVD). Statins are firstly indicated for the primary and secondary prevention of CVD, and thus individuals receiving statin therapy inherently have a higher risk of CVD or a confirmed diagnosis of CVD. Notably, CVD and its severity are significantly associated with an elevated risk of anxiety and depression. The included studies in the present meta-analysis exhibited inconsistencies in the definition and adjustment of CVD status, which may have contributed to the heterogeneity in effect sizes across individual studies and also represents a key driver of the high heterogeneity observed in this meta-analysis, further limiting the certainty of our conclusions. Finally, although the primary analysis using a random-effects model yielded a non-significant association between statin use and anxiety risk, the pooled estimate shifted to a statistically significant reduction in risk when a fixed-effects model was applied instead. The random-effects model is generally regarded as a more conservative approach for addressing heterogeneity. Given the small number of included studies and the aforementioned limitations, the null finding of no significant association in the present study must be interpreted with extreme caution.
Conclusion
Current evidence indicates that statin use is not associated with an increased risk of anxiety disorders. Future large-scale, prospective, multi-center cohort studies are warranted to further validate this finding.
Data availability statement
The original contributions presented in the study are included in the article/Supplementary material, further inquiries can be directed to the corresponding author/s.
The author(s) declared that this work was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Generative AI statement
The author(s) declared that generative AI was not used in the creation of this manuscript.
Any alternative text (alt text) provided alongside figures in this article has been generated by Frontiers with the support of artificial intelligence and reasonable efforts have been made to ensure accuracy, including review by the authors wherever possible. If you identify any issues, please contact us.
Publisher’s note
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.
Supplementary material
The Supplementary Material for this article can be found online at: https://www.frontiersin.org/articles/10.3389/fpsyt.2026.1769044/full#supplementary-material
ReferencesLakhawatSSMechPKumarAMalikNKumarVSharmaV.
Intricate mechanism of anxiety disorder, recognizing the potential role of gut microbiota and therapeutic interventions. Metab Brain Dis. (2024) 40:64. doi: 10.1007/s11011-024-01453-1, PMID: 39671133ZhangBLiYChuWLiYZhangJLvZ.
Efficacy of non-pharmacological interventions for alleviating insomnia in individuals with generalized anxiety disorder: systematic evaluation and net meta-analysis. Front Psychiatry. (2025) 16:1669888. doi: 10.3389/fpsyt.2025.1669888, PMID: 41244878BandelowBMichaelisS.
Epidemiology of anxiety disorders in the 21st century. Dialogues Clin Neurosci. (2015) 17:327–35. doi: 10.31887/DCNS.2015.17.3/bbandelow, PMID: 26487813GBD 2019 Mental Disorders Collaborators.
Global, regional, and national burden of 12 mental disorders in 204 countries and territories 1990-2019: A systematic analysis for the global burden of disease study 2019. Lancet Psychiatry. (2022) 9:137–50. doi: 10.1016/s2215-0366(21)00395-3, PMID: 35026139MeierSMMattheisenMMorsOMortensenPBLaursenTMPenninxBW.
Increased mortality among people with anxiety disorders: total population study. Br J psychiatry: J Ment Sci. (2016) 209:216–21. doi: 10.1192/bjp.bp.115.171975, PMID: 27388572ChisholmDSweenyKSheehanPRasmussenBSmitFCuijpersP.
Scaling-up treatment of depression and anxiety: A global return on investment analysis. Lancet Psychiatry. (2016) 3:415–24. doi: 10.1016/s2215-0366(16)30024-4, PMID: 27083119ChodavadiaPTeoIPoremskiDFungDSSFinkelsteinEA.
Prevalence and economic burden of depression and anxiety symptoms among Singaporean adults: results from a 2022 web panel. BMC Psychiatry. (2023) 23:104. doi: 10.1186/s12888-023-04581-7, PMID: 36782116DavisLLScheinJCloutierMGagnon-SanschagrinPMaitlandJUrganusA.
The economic burden of posttraumatic stress disorder in the United States from a societal perspective. J Clin Psychiatry. (2022) 83:1–9. doi: 10.4088/JCP.21m14116, PMID: 35485933Ghani KhanKKaurPBhagatMKlairHKBakhtawarMAldea SaldañaJM.
Effect of statin therapy on clinical outcomes in patients with cardiovascular risks: A systematic review and meta-analysis. Cureus. (2025) 17:e88238. doi: 10.7759/cureus.88238, PMID: 40831859XiaoXDengHLiPSunJTianJ.
Statin for mood and inflammation among adult patients with major depressive disorder: an updated meta-analysis. Front Psychiatry. (2023) 14:1203444. doi: 10.3389/fpsyt.2023.1203444, PMID: 38034928ChamSKoslikHJGolombBA.
Mood, personality, and behavior changes during treatment with statins: A case series. Drug Saf - Case Rep. (2016) 3:1. doi: 10.1007/s40800-015-0024-2, PMID: 27747681ChenJZhangCJiangHLiYZhangLRobinA.
Atorvastatin induction of vegf and bdnf promotes brain plasticity after stroke in mice. J Cereb Blood Flow metabolism: Off J Int Soc Cereb Blood Flow Metab. (2005) 25:281–90. doi: 10.1038/sj.jcbfm.9600034, PMID: 15678129ParentMAHottmanDAChengSZhangWMcMahonLLYuanLL.
Simvastatin treatment enhances nmdar-mediated synaptic transmission by upregulating the surface distribution of the glun2b subunit. Cell Mol Neurobiol. (2014) 34:693–705. doi: 10.1007/s10571-014-0051-z, PMID: 24687455AdzicMBrkicZMiticMFrancijaEJovicicMJRadulovicJ.
Therapeutic strategies for treatment of inflammation-related depression. Curr neuropharmacology. (2018) 16:176–209. doi: 10.2174/1570159x15666170828163048, PMID: 28847294PopGFarcașAButucăAMorgovanCArseniuAMPumneaM.
Post-marketing surveillance of statins-a descriptive analysis of psychiatric adverse reactions in eudravigilance. Pharm (Basel Switzerland). (2022) 15:1536. doi: 10.3390/ph15121536, PMID: 36558987ShrivastavaSPucadyilTJPailaYDGangulySChattopadhyayA.
Chronic cholesterol depletion using statin impairs the function and dynamics of human serotonin(1a) receptors. Biochemistry. (2010) 49:5426–35. doi: 10.1021/bi100276b, PMID: 20521763RepovaKAziriovaSKrajcirovicovaKSimkoF.
Cardiovascular therapeutics: A new potential for anxiety treatment? Medicinal Res Rev. (2022) 42:1202–45. doi: 10.1002/med.21875, PMID: 34993995ZhangLBaoYTaoSZhaoYLiuM.
The association between cardiovascular drugs and depression/anxiety in patients with cardiovascular disease: A meta-analysis. Pharmacol Res. (2022) 175:106024. doi: 10.1016/j.phrs.2021.106024, PMID: 34890773MoleroYCiprianiALarssonHLichtensteinPD’OnofrioBMFazelS.
Associations between statin use and suicidality, depression, anxiety, and seizures: A swedish total-population cohort study. Lancet Psychiatry. (2020) 7:982–90. doi: 10.1016/s2215-0366(20)30311-4, PMID: 33069320YangQYangZZengBJiaJSunF.
Association of statin use with risk of depression and anxiety: A prospective large cohort study. Gen Hosp Psychiatry. (2024) 90:108–15. doi: 10.1016/j.genhosppsych.2024.07.015, PMID: 39106577YeXBlaisJENgVWSCastleDHayesJFWeiY.
Association between statins and the risk of suicide attempt, depression, anxiety, and seizure: A population-based, self-controlled case series study. J Affect Disord. (2023) 320:421–7. doi: 10.1016/j.jad.2022.09.148, PMID: 36206879ChenZJiangTPengYQiangXYangFHuH.
Acupuncture and moxibustion treating lower urinary tract symptoms due to benign prostatic hyperplasia: A systematic review and network meta-analysis. Acupuncture Herbal Med. (2022) 2:84–90. doi: 10.1097/HM9.0000000000000029PageMJMcKenzieJEBossuytPMBoutronIHoffmannTCMulrowCD.
The prisma 2020 statement: an updated guideline for reporting systematic reviews. BMJ (Clinical Res ed). (2021) 372:n71. doi: 10.1136/bmj.n71, PMID: 33782057ZhuZYuanXZhengYDouBLiuLLohPY.
Effectiveness of acupuncture in managing aromatase inhibitor-related arthralgia in breast cancer: A systematic review and meta-analysis. Acupuncture Herbal Med. (2025) 5:352–65. doi: 10.1097/HM9.0000000000000172YehJJSyueSHLinCLHsuCYShaeZKaoCH.
Effects of statins on anxiety and depression in patients with asthma-chronic obstructive pulmonary disease overlap syndrome. J Affect Disord. (2019) 253:277–84. doi: 10.1016/j.jad.2019.05.002, PMID: 31071545Young-XuYChanKALiaoJKRavidSBlattCM.
Long-term statin use and psychological well-being. J Am Coll Cardiol. (2003) 42:690–7. doi: 10.1016/s0735-1097(03)00785-x, PMID: 12932603SalagreEFernandesBSDoddSBrownsteinDJBerkM.
Statins for the treatment of depression: A meta-analysis of randomized, double-blind, placebo-controlled trials. J Affect Disord. (2016) 200:235–42. doi: 10.1016/j.jad.2016.04.047, PMID: 27148902KwakBMulhauptFVeillardNPelliGMachF.
The hmg-coa reductase inhibitor simvastatin inhibits ifn-gamma induced mhc class ii expression in human vascular endothelial cells. Swiss Med weekly. (2001) 131:41–6. doi: 10.4414/smw.2001.06144, PMID: 11219190O’NeilASannaLRedlichCSandersonKJackaFWilliamsLJ.
The impact of statins on psychological wellbeing: A systematic review and meta-analysis. BMC Med. (2012) 10:154. doi: 10.1186/1741-7015-10-154, PMID: 23206308VcJBalajiOChogtuB.
Effect of different statins in animal model of anxiety in wistar rats. Asian J Pharm Clin Res. (2018) 11:369–71. doi: 10.22159/ajpcr.2018.v11i10.24222SantosTBaungratzMMHaskelSPde LimaDDda CruzJNMagroDD.
Behavioral interactions of simvastatin and fluoxetine in tests of anxiety and depression. Neuropsychiatr Dis Treat. (2012) 8:413–22. doi: 10.2147/ndt.s31714, PMID: 23055736GuoBZhangMHaoWWangYZhangTLiuC.
Neuroinflammation mechanisms of neuromodulation therapies for anxiety and depression. Trans Psychiatry. (2023) 13:5. doi: 10.1038/s41398-022-02297-y, PMID: 36624089AvanRSahebnasaghAHashemiJMonajatiMFaramarziFHenneyNC.
Update on statin treatment in patients with neuropsychiatric disorders. Life (Basel Switzerland). (2021) 11:1365. doi: 10.3390/life11121365, PMID: 34947895VeveraJValešKFišarZHroudováJSinghNStuchlíkA.
The effect of prolonged simvastatin application on serotonin uptake, membrane microviscosity and behavioral changes in the animal model. Physiol Behav. (2016) 158:112–20. doi: 10.1016/j.physbeh.2016.02.029, PMID: 26917054OlmastroniEMolariGDe BeniNColpaniOGalimbertiFGazzottiM.
Statin use and risk of dementia or alzheimer’s disease: A systematic review and meta-analysis of observational studies. Eur J Prev Cardiol. (2022) 29:804–14. doi: 10.1093/eurjpc/zwab208, PMID: 34871380YeniYCicekBHacimuftuogluAOzkaracaMLacinBB.
Protective effect of hmg-coa reductase inhibitor rosuvastatin on doxorubicin-induced cognitive impairment, oxidative stress and neuroinflammation: possible role of creb, erk1/2, and BDNF. J neuroimmune pharmacology: Off J Soc NeuroImmune Pharmacol. (2025) 20:53. doi: 10.1007/s11481-025-10213-6, PMID: 40358798
Edited by: Sohail Akhtar, The University of Haripur, Pakistan
Reviewed by: Bo Ning, Guangzhou University of Chinese Medicine, China