Introduction
Olfactory dysfunction is characterised by a diminished or distorted sense of smell.Reference Whitcroft and Hummel1 Its reported prevalence varies according to assessment methods and age, with pooled estimates indicating that approximately 22 per cent of the general population is affected.Reference Desiato, Levy, Byun, Nguyen, Soler and Schlosser2 The most common aetiologies include sinonasal disease, post-upper respiratory infection loss and head trauma.Reference Hummel, Liu, Müller, Stuck, Welge-Lüssen and Hähner3 A variety of interventions, such as antibiotics, topical or systemic corticosteroids, endoscopic sinus surgery and anti-allergic medications, have been proposed.Reference Moon, Chon, Lee, Ju and Sung4 More recently, strategies that include olfactory training, vitamin A, theophylline and sodium citrate have been recommended for refractory olfactory dysfunction, but their clinical efficacy remains limited.Reference Farrell, Crock, Islam, Adkins, Peterson and Kallogjeri5
Stellate ganglion block suppresses sympathetic neural activity and reduces circulating catecholamine levels.Reference Liu and Duricka6 It has been applied in various conditions, including post-traumatic stress disorder, migraine and complex regional pain syndrome.Reference Kirkpatrick, Khan, Deng and Shah7 Although the mechanisms by which stellate ganglion block may affect olfaction remain unclear, several studies have reported potential benefits in olfactory dysfunction.Reference Kirkpatrick, Khan, Deng and Shah7–Reference Peterson, Miller, Kallogjeri, Piccirillo, Kukuljan and Roland9 However, studies regarding objective olfactory outcomes and olfaction-related quality of life (QoL) are limited, and most studies are constrained by small sample sizes.Reference Farrell, Crock, Islam, Adkins, Peterson and Kallogjeri5, Reference Naimi, Garvey, Chandna, Duffy, Hunter and Mandloi10 We therefore conducted a systematic review and meta-analysis to evaluate quantitatively the therapeutic efficacy of stellate ganglion block in patients with refractory and persistent olfactory dysfunction.
Materials and methods
Search strategy and study selection
The population, intervention, comparison and outcomes framework was defined as follows: the population comprised patients with chronic-onset olfactory dysfunction persisting for more than six months and refractory to established treatments, the intervention was stellate ganglion block, the comparison was not restricted and the outcomes included changes in olfactory symptom scores assessed using validated measures such as smell identification tests, the butanol threshold test or the Sniffin’ Sticks test (threshold, discrimination and identification), as well as olfactory dysfunction-related QoL. This systematic review was conducted in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines.Reference Whitcroft and Hummel1
The following electronic databases were searched for relevant studies published before December 2025: PubMed, Scopus, Embase, Web of Science, Google Scholar and the Cochrane Library. Our search terms included ‘anosmia’, ‘hyposmia’, ‘olfactory’, ‘smell’, ‘olfactory disorders’, ‘olfactory dysfunctions’, ‘recovery’, ‘olfactory test’, ‘stellate ganglion block’ and ‘treatment’. Detailed search terms and queries, and detailed search strategies are presented in Supplementary Table S1. Titles and abstracts were screened independently by two reviewers, with full-text assessment performed as needed. Discrepancies were resolved through consultation with a third reviewer, and authors were contacted to obtain missing or incomplete data.
Studies were excluded if olfactory dysfunction was secondary to obstructive or inflammatory lesions, reports were duplicates or quantitative data were insufficient. The study selection process is depicted in Figure 1. The study protocol was registered with the Open Science Framework (https://osf.io/sy736/).
Flow diagram depicting the study selection process.
Figure 1 Long description
The flowchart outlines the study identification and selection process. It begins with 'Identification' where records are identified from databases such as PubMed, Cochrane Central Register of Controlled Trials, Embase, Web of Science, Scopus and Google Scholar, totaling 241 records. Next, 'Records removed before screening' shows 152 duplicate records removed. 'Screening' follows with 89 records screened and 67 records excluded after screening of title or abstract. 'Reports sought for retrieval' includes 22 reports, with 2 not retrieved. 'Reports assessed for eligibility' involves 20 reports, with 11 excluded due to reasons like no relevant data. Finally, 'Included' shows 9 reports of included studies.
Data extraction and risk of bias assessment
Data from eligible studies were systematically extracted using a standardised collection form.Reference Kim, Jang and Hwang11, Reference Kim, Jang and Hwang12 Extracted variables included sample size, olfactory dysfunction grading scales, serum glucose and insulin levels, the incidence or proportion of patients achieving substantial recovery from olfactory dysfunction and p values for comparisons between treatment and control groups or between pre- and post-treatment outcomes. The primary outcomes were changes in olfactory scores, assessed by subjective symptom scales or objective olfactory tests, and olfactory dysfunction-related QoL. Secondary outcomes included the proportion of patients demonstrating significant subjective or objective recovery and clinically meaningful improvement in QoL. Because most included studies were single-arm cohort studies, outcome data were primarily derived from within-group comparisons between pre- and post-intervention measurements. When available, between-group comparisons were extracted separately from studies that included a control group. Accordingly, analyses were conducted by distinguishing within-group pre–post changes from direct treatment–control comparisons to accurately reflect differences in study design and available evidence.
Objective olfactory function was assessed using a variety of instruments, including the Connecticut Chemosensory Clinical Research Center test (n-butanol threshold and smell identification), the Brief Smell Identification Test, the University of Pennsylvania Smell Identification Test and the Korean version of the Sniffin’ Sticks test. Each study used its own scoring system for olfactory dysfunction, and no standardised criteria for substantial recovery were defined; recovery was determined according to study-specific objective measures or symptom scores.
Olfactory dysfunction-related QoL was evaluated using the olfactory dysfunction outcomes rating questionnaire, a validated patient-reported outcome measure with a minimal clinically important difference of 15 points.Reference Lee, Mahadev, Kallogjeri, Peterson, Gupta and Khan13 Risk of bias in randomised controlled trials was assessed using the Cochrane risk of bias tool, whereas non-randomised studies were evaluated using the Newcastle–Ottawa Scale (range, 0–9) (Supplementary Tables S2 and S3).
Statistical analysis
Statistical analyses were performed using R statistical software (version 4.3.2; R Foundation for Statistical Computing, Vienna, Austria). For outcomes reported as continuous variables, effect sizes were calculated using standardised mean differences (SMDs) because outcome measures of olfactory function were not uniform across studies, including the Connecticut Chemosensory Clinical Research Center test and the Sniffin’ Sticks test. For outcomes reported as event data, incidence analyses were conducted using proportions.
Results
This meta-analysis included 9 studies comprising 441 participants.Reference Moon, Chon, Lee, Ju and Sung4, Reference Farrell, Crock, Islam, Adkins, Peterson and Kallogjeri5, Reference Park, Kim, Bae and Lee8–Reference Naimi, Garvey, Chandna, Duffy, Hunter and Mandloi10, Reference Galvin, Cheek, Zhang, Collins and Gaskin14–Reference Duricka and Liu17 Among the included studies, one was a randomised controlled trial with a placebo control, whereas the remaining studies were cohort studies primarily reporting pre- and post-intervention outcomes without a parallel control group. All nine studies reported subjective or objective olfactory outcomes assessed from pre-treatment to post-treatment or the incidence of subjective or objective improvement, and direct treatment–control comparisons were available only in the randomised controlled trial. Table 1 presents the detailed characteristics of the included studies and the corresponding risk-of-bias assessments.
Study characteristics
Table 1 Long description
The table summarizes nine studies on interventions for olfactory dysfunction, listing design, sample size, participant demographics, cause of smell loss, treatment schedule, follow-up, and outcomes measured. Most studies are cohort designs, with one randomized placebo-controlled trial. Earlier studies from Korea focus on post upper respiratory infection cases, while later studies from the United States primarily involve post Covid smell loss. Sample sizes range from 10 to 195 participants, with mean ages generally in the mid to late forties through late fifties, and sex distributions often skew female in the US post Covid cohorts. Duration of dysfunction varies widely, from about a few months to multiple years, and is not reported in some studies. Administration schedules differ substantially, from frequent weekly sessions over several weeks to ipsilateral or bilateral blocks, with follow-up ranging from several days to three months and sometimes not defined. Outcomes commonly include objective olfactory testing and subjective symptom scores, with several studies also tracking improvement rates, adverse effects, and quality of life related olfactory function. Comparisons across studies are limited by inconsistent reporting of age formats, duration measures, follow-up timing, and outcome definitions.
SD = standard deviation; M = male; F = female; upper respiratory infection (URI) =; ND = not defined; Covid-19 = coronavirus disease 2019; RCT = randomised, double-blinded, placebo-controlled clinical trial; QoL = quality of life
Changes in olfactory scores between the treatment and control groups
Between-group comparisons were derived from studies in which control data were available, while pooled estimates from cohort studies reflect within-group pre–post changes. Improvement in olfactory composite scores (identification, threshold and discrimination) from pre-treatment to post-treatment was greater in the stellate ganglion block group (SMD = −0.7630, 95 per cent confidence interval [CI] = −1.1830 to −0.3429, I 2 = 0.0 per cent) compared with the control group (SMD = −0.1412, 95 per cent CI = −0.7079 to 0.4254, I 2 = 0.0 per cent); however, the between-group difference was not statistically significant (p = 0.0841; Figure 2A).
Comparison of olfactory outcomes between stellate ganglion block and control interventions: olfactory composite score (A), olfactory identification score (B) and subjective olfactory function (C). SD = standard deviation; SMD = standardised mean difference.
Figure 2 Long description
A. Comparison of olfactory outcomes between stellate ganglion block and control interventions: olfactory composite score (A), olfactory identification score (B) and subjective olfactory function (C). The forest plot lists studies with columns: Study, Total, Mean, Pre-treat SD, Total, Mean, Post-treat SD, Standardised mean difference, SMD, 95 percent CI, Weight (common), Weight (random). The horizontal scale is labelled Standardised mean difference, with tick labels at minus 1.5, minus 1, minus 0.5, 0, 0.5, 1, 1.5. For g2 treatment group, study rows include Lee (2003), Park (2013) and Random effects model. SMD values shown include minus 0.81 with 95 percent CI minus 1.28 to minus 0.34, minus 0.56 with 95 percent CI minus 1.51 to 0.39 and minus 0.76 with 95 percent CI minus 1.18 to minus 0.34. Heterogeneity line shows I2 equals 0.0 percent, tau squared equals 0, p equals 0.6370. For g2 control group, study rows include Lee (2003), Park (2013) and Random effects model. SMD values shown include minus 0.12 with 95 percent CI minus 0.89 to 0.65, minus 0.17 with 95 percent CI minus 1.00 to 0.67 and minus 0.14 with 95 percent CI minus 0.71 to 0.43. Heterogeneity line shows I2 equals 0.0 percent, tau squared equals 0, p equals 0.9346. A pooled section shows Common effect model and Random effects model with SMD minus 0.54 and 95 percent CI minus 0.88 to minus 0.21 and SMD minus 0.50 and 95 percent CI minus 0.90 to minus 0.10. Total weight lines show 100.0 percent for common and 100.0 percent for random. Test for overall effect shows z equals 6.79, p less than 0.0001 and z equals 2.98, p equals 0.0841. Test for subgroup differences shows z equals 2.98, p equals 0.0841. B. The forest plot uses the same columns and the same Standardised mean difference scale with tick labels at minus 1.5, minus 1, minus 0.5, 0, 0.5, 1, 1.5. For g2 treatment group, study rows include Lee (2003), Park (2013) and Random effects model. SMD values shown include minus 0.54 with 95 percent CI minus 1.00 to minus 0.08, minus 0.12 with 95 percent CI minus 0.50 to 0.24, minus 0.78 with 95 percent CI minus 1.42 to minus 0.13 and Random effects model minus 0.41 with 95 percent CI minus 0.89 to 0.08. Heterogeneity line shows I2 equals 53.8 percent, tau squared equals 0.1006, p equals 0.1148. For g2 control group, the study row includes Lee (2003). SMD is 0.00 with 95 percent CI minus 0.77 to 0.77. A pooled section shows Common effect model and Random effects model with SMD minus 0.36 and 95 percent CI minus 0.65 to minus 0.06 and SMD minus 0.33 and 95 percent CI minus 0.74 to 0.07. Total weight lines show 100.0 percent for common and 100.0 percent for random. Heterogeneity line shows I2 equals 43.5 percent, tau squared equals 0.0745, p equals 0.1503. Test for subgroup differences shows z equals 0.96, p equals 0.3215 and z equals 0.76, p equals 0.3821. C. The forest plot uses the same columns and a Standardised mean difference scale with tick labels at minus 2, minus 1, 0, 1, 2. For g2 treatment group, study rows include Lee (2003), Park (2013), Main (2024), Peirce (2024), Durkin (2024), Farrell (2025) and Random effects model. SMD values shown include minus 1.34 with 95 percent CI minus 1.84 to minus 0.84, minus 0.79 with 95 percent CI minus 1.27 to minus 0.32, minus 0.88 with 95 percent CI minus 1.86 to 0.10, minus 0.76 with 95 percent CI minus 1.24 to minus 0.29, minus 0.64 with 95 percent CI minus 1.65 to 0.37, minus 0.81 with 95 percent CI minus 1.33 to minus 0.29 and Random effects model minus 1.02 with 95 percent CI minus 1.25 to minus 0.79. Heterogeneity line shows I2 equals 43.5 percent, tau squared equals 0.0827, p equals 0.1008. For g2 control group, study rows include Lee (2003), Park (2013), Farrell (2025) and Random effects model. SMD values shown include minus 0.11 with 95 percent CI minus 0.88 to 0.66, minus 0.98 with 95 percent CI minus 1.87 to minus 0.10, minus 0.57 with 95 percent CI minus 1.28 to 0.14 and Random effects model minus 0.52 with 95 percent CI minus 0.97 to minus 0.07. Heterogeneity line shows I2 equals 59.9 percent, tau squared equals 0.0001, p equals 0.3457. A pooled section shows Common effect model and Random effects model with SMD minus 0.92 and 95 percent CI minus 1.12 to minus 0.71 and SMD minus 0.89 and 95 percent CI minus 1.18 to minus 0.60. Total weight lines show 100.0 percent for common and 100.0 percent for random. Heterogeneity line shows I2 equals 45.6 percent, tau squared equals 0.1013, p equals 0.0562. Test for subgroup differences shows z equals 3.81, p equals 0.0511 and z equals 3.81, p equals 0.0783.
Similarly, improvement in olfactory identification scores favoured the stellate ganglion block group (SMD = −0.4212, 95 per cent CI = −0.7411 to −0.1012, I 2 = 53.8 per cent) compared with the control group (SMD = 0.0000, 95 per cent CI = −0.7688 to 0.7688, I 2 = not applicable); however, the between-group difference was not statistically significant (p = 0.3215; Figure 2B).
Improvements in subjective olfactory function were greater in the stellate ganglion block group (SMD = −1.0193, 95 per cent CI = −1.2475 to −0.7911, I 2 = 43.5 per cent) compared to the control group (SMD = −0.5167, 95 per cent CI = −0.9671 to −0.0664, I 2 = 5.9 per cent), although this difference did not reach statistical significance (p = 0.0511; Figure 2C).
Proportion of patients with significant olfactory recovery or quality of life improvement
The pooled proportions of subjective and objective olfactory improvement in the stellate ganglion block group were 0.6893 (95 per cent CI = 0.5583–0.7956, I 2 = 62.1 per cent) and 0.6338 (95 per cent CI = 0.5164–0.7372, I 2 = 2.5 per cent), respectively; these outcomes were not directly compared with the control group (Figure 3A).
Proportions of participants demonstrating significant recovery from olfactory dysfunction based on subjective (A) and objective (B) assessments, and improvement in olfaction-related quality of life (C).
Figure 3 Long description
The image A showing a forest plot with columns labeled Study, Events, Total, Proportion and 95 percent CI. The x-axis is labeled Proportion, with tick labels 0.3, 0.4, 0.5, 0.6, 0.7 and 0.8. The y-axis lists studies under the subgroup label “g2 = treatment group.” Events indicates the count in the Events column and Total indicates the count in the Total column. Studies and values: Lee (2003) Events 29, Total 38, Proportion 0.76, 95 percent CI 0.60 to 0.89; Moon (2007) Events 7, Total 13, Proportion 0.54, 95 percent CI 0.25 to 0.81; Galvin (2023) Events 147, Total 195, Proportion 0.75, 95 percent CI 0.69 to 0.81; Peterson (2024) Events 10, Total 20, Proportion 0.50, 95 percent CI 0.27 to 0.73. Random effects model: Total 266, Proportion 0.69, 95 percent CI 0.56 to 0.80. Heterogeneity: I superscript 2 equals 62.1 percent, tau superscript 2 equals 0.1083, p equals 0.0476. The image B showing a forest plot with columns labeled Study, Events, Total, Proportion and 95 percent CI. The x-axis is labeled Proportion, with tick labels 0.3, 0.4, 0.5, 0.6, 0.7 and 0.8. The y-axis lists studies under the subgroup label “g2 = treatment group.” Events indicates the count in the Events column and Total indicates the count in the Total column. Studies and values: Lee (2003) Events 27, Total 38, Proportion 0.71, 95 percent CI 0.54 to 0.85; Moon (2007) Events 7, Total 13, Proportion 0.54, 95 percent CI 0.25 to 0.81; Peterson (2024) Events 11, Total 20, Proportion 0.55, 95 percent CI 0.32 to 0.77. Random effects model: Total 71, Proportion 0.63, 95 percent CI 0.52 to 0.74. Heterogeneity: I superscript 2 equals 2.5 percent, tau superscript 2 equals 0, p equals 0.3588. The image C showing a forest plot with columns labeled Study, Events, Total, Proportion and 95 percent CI. The x-axis is labeled Proportion, with tick labels 0.2, 0.3, 0.4, 0.5 and 0.6. The y-axis lists studies grouped under “g2 = treatment group” and “g2 = control group.” Events indicates the count in the Events column and Total indicates the count in the Total column. Treatment group studies and values: Peterson (2024) Events 6, Total 20, Proportion 0.30, 95 percent CI 0.12 to 0.54; Farrel (2025) Events 13, Total 31, Proportion 0.42, 95 percent CI 0.25 to 0.61. Treatment group random effects model: Total 51, Proportion 0.37, 95 percent CI 0.25 to 0.51. Treatment group heterogeneity: I superscript 2 equals 0 percent, tau superscript 2 equals 0, p equals 0.9313. Control group study and values: Farrel (2025) Events 6, Total 16, Proportion 0.38, 95 percent CI 0.15 to 0.65. Control group random effects model: Total 67, Proportion 0.37, 95 percent CI 0.27 to 0.49. Control group heterogeneity: I superscript 2 equals 0 percent, tau superscript 2 equals 0, p equals 0.8925. Test for subgroup differences: chi superscript 2 equals 0.00, df equals 1, p equals 0.9889.
Olfaction-related QoL outcomes were assessed in both groups. The proportion of patients achieving a clinically meaningful improvement in QoL was comparable between the stellate ganglion block group (0.3725, 95 per cent CI = 0.2518–0.5116, I 2 = 0.0 per cent) and the control group (0.3750, 95 per cent CI = 0.1790–0.6228, I 2 = NA), with no statistically significant between-group differences (p = 0.9859; Figure 3B).
No major adverse events were reported following stellate ganglion block. One study documented a single case of accidental brachial plexus block among 37 patients. Transient and mild adverse events, including voice change, nasal congestion, dizziness and headache, were reported in two studies (Figure 3C).
Discussion
In our study, stellate ganglion block was associated with within-group improvements in both objective and subjective olfactory outcomes compared with baseline, primarily derived from single-arm studies. However, none of the between-group comparisons for olfactory scores reached statistical significance. Clinically meaningful recovery and QoL improvement were observed in a substantial proportion of patients receiving stellate ganglion block, although these findings should be interpreted with caution given the limited controlled evidence, and the intervention demonstrated a safety profile predominantly characterised by transient and mild adverse events, as reported in the included studies, suggesting a potential but unconfirmed therapeutic role in refractory olfactory dysfunction.
Stellate ganglion block has been postulated to suppress sympathetic neural activity in the head, neck and upper extremities, enhancing regional perfusion, reducing circulating stress-related hormones and restoring circadian regulation through effects on melatonin signalling. Based on these mechanisms, stellate ganglion block has been applied in several disorders characterised by dysregulated neuroimmune interactions, including complex regional pain syndrome, post-traumatic stress disorder and migraine.
Several pathophysiological mechanisms have been proposed to explain the potential therapeutic effects of stellate ganglion block in olfactory dysfunction. One mechanism involves sympathetic inhibition-induced increases in cerebral and facial blood flow, which may enhance perfusion of both central olfactory structures and peripheral olfactory receptors.Reference Liu and Duricka6 Considering the regenerative capacity of the olfactory bulb, augmented blood supply to the bulb and its associated neural pathways could facilitate neural repair and functional recovery.Reference Thottungal and Parameswaran18 Notably, the clinical benefits of stellate ganglion block often persist beyond the pharmacological duration of local anaesthetics, implying that mechanisms beyond transient sympathectomy-mediated perfusion enhancement are likely involved.
Another plausible explanation involves the close interplay between the sympathetic nervous system and immune regulation. Sympathetic activation can elicit diverse immunomodulatory responses that are proinflammatory, anti-inflammatory or context dependent, varying with the location and chronicity of inflammation.Reference Schaible and Straub19 Inflammatory mediators contribute to olfactory neuronal injury by altering neuronal ion channel activity, particularly potassium channels, and by exerting cytotoxic effects that impair axonal growth, neurotransmitter release and neuroendocrine regulation.Reference Zhang, Zhang, Ba, Wu and Wang20 Therefore, temporary interruption of sympathetic overactivity via stellate ganglion block may restore autonomic balance and normalise immune responses, mitigating inflammation-induced neuronal dysfunction. Overall, the potential mechanisms of stellate ganglion block likely include peripheral and central sympathetic modulation, enhanced cerebral blood flow and restoration of neuroimmune balance. However, further mechanistic studies are needed to substantiate these hypotheses and clarify the role of stellate ganglion block in the management of olfactory dysfunction.Reference Liu and Duricka6
Our study has several limitations. First, the included data were derived from only two countries, South Korea and the USA, raising concerns regarding the generalisability of the findings, as the clinical characteristics and aetiologies of olfactory dysfunction—including post-upper respiratory infection and other causes—may differ across regions. Moreover, more than half of the included studies focused on post-coronavirus disease 2019 olfactory dysfunction, which may further restrict the applicability of the results to broader patient populations.
Second, substantial heterogeneity was observed in olfactory outcome measures, likely reflecting differences in patient characteristics, stellate ganglion block protocols and assessment methods across studies. Notably, the frequency of stellate ganglion block administration varied significantly by country, with studies from South Korea typically involving approximately 10 sessions, whereas those from the USA generally reported only 1 or 2.
Third, most studies assessed outcomes over relatively short follow-up periods, emphasising the need for long-term evaluations to determine the durability of olfactory improvement. Finally, although stellate ganglion block was associated with improvements in olfactory function and olfaction-related QoL within treated groups, these findings were primarily derived from within-group analyses and did not demonstrate statistically significant superiority over control interventions. Therefore, any apparent benefits should be interpreted cautiously and considered preliminary.
Future studies should address these limitations through prospective, multicentre studies with extended follow up, standardised intervention protocols and robust objective outcome measures to define the long-term efficacy and safety of stellate ganglion block more clearly.
• Stellate ganglion block was associated with within-group improvements in objective olfactory composite scores, but without statistically significant differences compared with controls
• Olfactory identification scores showed improvement in pooled analyses following stellate ganglion block, but no significant advantage over controls
• Subjective olfactory function showed improvement in pooled analyses after stellate ganglion block, but did not differ significantly from controls
• Many patients receiving stellate ganglion block showed subjective and objective olfactory improvement, although these findings were primarily derived from single-arm studies, while quality of life gains were similar between groups
• Stellate ganglion block was not associated with major adverse events in the included studies, with only rare, mild and transient complications reported
Conclusion
Stellate ganglion block is a safe intervention that may confer modest improvements in objective and subjective olfactory outcomes in patients with persistent, refractory sensorineural olfactory dysfunction. However, the lack of statistically significant differences compared with control groups precludes definitive conclusions regarding its therapeutic superiority. These findings emphasise the need for rigorously designed, placebo-controlled randomised trials with standardised outcome measures and extended follow up to clarify the clinical efficacy and durability of stellate ganglion block in this patient population.
Supplementary material
The supplementary material for this article can be found at https://doi.org/10.1017/S0022215126104769.
Acknowledgements
The English in this document has been checked by at least two professional editors, both native speakers of English. For a certificate, please see http://www.textcheck.com/certificate/R0WzAC.
