Selective serotonin re-uptake inhibitors and risks of post-operative hematoma after elbow fracture surgery

Abstract

Background

Selective serotonin re-uptake inhibitors (SSRIs) and serotonin-norepinephrine re-uptake inhibitors (SNRIs) are commonly prescribed medications for depression, anxiety, and other comorbid psychiatric conditions. However, these medications can have off-target effects, such as lowering platelet serotonin levels and reducing the ability of platelets to aggregate, which may lead to higher rates of post-operative bleeding. The aim of this paper was to determine if SSRIs/SNRIs increase the risk of post-operative hematoma formation following traumatic elbow surgery.

Methods

Adult patients who underwent elbow fracture surgery between 2009 and 2022 were reviewed retrospectively utilizing a national administrative claims database. Exclusion criteria included patients who sustained a pathological fracture, open fracture, had an active infection, or hematologic disorder at the time of surgery. Patients were divided into those who were not prescribed SSRIs/SNRIs (control) and those prescribed SSRIs/SNRIs within 90 days pre-operatively (treatment). Patient cohorts were then propensity-score matched in a 1:3 ratio. Multivariable logistic regression was performed to assess 30- and 90-day outcomes.

Results

Over 6,000 patients were included in the initial query. After propensity-score matching, 985 patients were included in the control group (no SSRI/SNRI) and 2,494 patients in the treatment (SSRI/SNRI) group. At 30 days post-operatively, patients in the treatment group had a significantly greater rate of Surgical Site Infection (SSI) (3.4% vs. 2.2%; P = .04). There was no significant difference in rates of 30-day hematomas between the 2 cohorts. At 90 days post-operatively, there was a statistically significant difference in complications for patients treated with SSRI/SNRIs, including a higher rate of SSI (5.4% vs. 3.3%; P = .01) and hematoma formation (1.2% vs. 0.6%; P = .04).

Conclusion

SSRIs and SNRIs are commonly prescribed to patients for a variety of psychiatric conditions. These medications often go unnoticed in the pre-operative surgical assessment; however, this retrospective study suggests an association between SSRI/SNRI use and higher odds of SSI and hematoma formation.

Hematoma formation following elbow surgery is a relatively rare complication, ranging from 4 to 13% depending on the type of procedure.^11,21,39 Despite this, they can potentially lead to more devastating complications. Studies have found that post-operative hematoma formation can serve as a nidus for bacteria through the creation of a nutrient-dense dead space,^21,29 leading to peri-implant infections,^11,21 or soft-tissue necrosis through shearing and pressure-related forces.^7,24,35 Neurovascular compromise has even been reported due to the expansile nature of the fluid collection.^8,12,27

The risk factors for post-operative hematoma formation are well documented and include the use of antiplatelet drugs, older age, longer operative times, higher comorbidity profile, active smoking, and history of bleeding disorder.^16,29,32,38 Selective serotonin re-uptake inhibitors (SSRIs) and selective serotonin-norepinephrine re-uptake inhibitors (SNRIs) represent an often-overlooked potential contributor to perioperative bleeding risk, as they inhibit serotonin re-uptake in platelets via blockade of the serotonin transporter, thereby impairing platelet aggregation and exerting an antiplatelet effect.^4,15,18, 19, 20^,26,31

While the association between perioperative SSRI use and post-operative bleeding complications, including hematoma formation, has been demonstrated in hip and knee arthroplasty,^34,36 femur fractures,³² and spinal surgery,¹ the impact on upper-extremity procedures remains poorly understood. One study following total elbow arthroplasty showed an increased risk of deep infection for patients on SSRIs/SNRIs;^21,39 however, no studies have evaluated the relationship between SSRI/SNRI use and post-operative hematoma or bleeding risk after traumatic elbow surgeries. This study aimed to address this gap by assessing SSRI- and SNRI-related bleeding risk in elbow fracture surgery.

Methods

Data source

This study was conducted in accordance with the REporting of studies Conducted using Observational Routinely-collected health Data guidelines.⁶ Patients were identified from the Merative MarketScan Commercial Claims and Encounters and Medicare Supplemental and Coordination of Benefit databases (Ann Arbor, Michigan). This database is a collection of medical insurance claims databases from over 300 employer-sponsored and Medicare supplemental plans, containing more than 240 million deidentified patient records. It provides information on inpatient admissions, outpatient visits, and pharmaceutical encounters. The authors chose to use this database because it contains data on a large quantity of continuously enrolled patients that allows for longitudinal follow up. Institutional review board approval was not required for this study because the Merative MarketScan database contains fully deidentified patient information and does not include protected health information. As a result, this study does not meet the definition of human subjects research.

Study cohort

Adult patients (≥18 years) between January 1, 2009, to December 31, 2022, who underwent surgery after an acute elbow fracture were identified using Current Procedural Terminology (CPT) codes. The CPT codes “24545,” “24546,” “24575,” “24579,” “24586,” and “24587” were utilized to identify patients who underwent distal humerus fixation. CPT codes “24665,” “24666,” and “24130” were used to identify radial head surgeries, and CPT “24685” was used for olecranon fixation. Patients were also required to have an associated diagnosis for elbow fracture at the time of surgery based on the International Classification of Disease, Ninth and Tenth editions (ICD-9 and ICD-10). For patients with multiple procedures on the same date, only the primary CPT code was used to avoid duplicate entries. To be included in the final analysis, patients were required to be enrolled in the database for at least 3 months pre- and post-operatively.

Patients were excluded from the study if they sustained an open elbow fracture, pathological elbow fracture, had an active osteomyelitis or septic arthritis, history of metastatic or solid cancer, or hematological bleeding disorder such as hemophilia, vitamin K deficiency, or von Willebrand disease. Patients who were on any anticoagulation or antiplatelet medications at the time of surgery were also excluded from the study. However, it is important to note that given that this study utilized a prescription claims database, patients on aspirin may not have been fully excluded from the study. Nonetheless, these exclusions were chosen to reduce potential confounding effects related to other pathologies that may independently impact bleeding or hematoma risk.

Following this, patients were then classified into 2 groups based on outpatient pharmacy prescription claims. The first group included those on an SSRI/SNRI prior to surgery (categorized into the treatment group), while the control group included those who were not on an SSRI/SNRI. To identify patients in the treatment group, the database was queried for either an SSRI (including fluoxetine, sertraline, citalopram, escitalopram, paroxetine, fluvoxamine, or vilazodone) or SNRI (including venlafaxine, duloxetine, desvenlafaxine, or levomilnacipran) prescription filled within 90 days pre-operatively. Only oral medications were considered. Patients who did not fill such a prescription within that time frame were allocated to the control group.

Cohort matching and covariate control

Baseline patient demographics and comorbidities were collected including age, sex, Charlson Comorbidity Index (CCI), diabetes mellitus, obesity (body mass index ≥30), smoking status, atrial fibrillation, major depressive disorder, and anxiety. The CCI is a comorbidity tool that is widely utilized to measure patients' burden of disease, which includes cardiovascular, neurologic, pulmonary, renal, and other chronic diseases.¹⁰

To adjust for baseline differences between cohorts, patients were propensity score matched in a 1:3 ratio using a nearest neighbor matching algorithm with a caliper of 0.01 standard deviations of the logit of the propensity score.⁵ Covariates included in the propensity model were age, sex, diabetes mellitus, obesity, smoking status, and CCI score. A 1:3 ratio was selected to preserve statistical power while ensuring balance in baseline characteristics relevant to post-operative bleeding risk. Covariate balance was assessed using standardized mean differences (SMDs), with values < 0.2 considered acceptable.⁵

Study outcomes and data analyses

Study outcomes included 30- and 90-day post-operative Surgical Site Infections (SSIs), wound dehiscence, hematoma, seroma, incision and drainage (I&D), and blood transfusions. I&D procedures were identified using CPT codes “23931,” “23930,” “10160,” and “10140”. Blood transfusions were only queried for within the 30-day period using CPT codes “36430,” “36440,” and “36455.” All other post-operative complications were identified with ICD-9 and ICD-10 diagnostic codes.

Descriptive statistics were used to compare baseline demographics and comorbidities before and after propensity-score matching. Student t-tests and chi-square tests were performed for continuous and categorical variables, as indicated. SMDs were used to confirm covariate balance after matching, with values < 0.2 considered acceptable. Multivariable logistic regression was used on the unmatched and matched cohorts to identify the association between SSRI/SNRI use and post-operative complications, adjusting for residual comorbidity imbalances. A subgroup analysis was also performed to confirm rates of 30-day and 90-day SSI between cohorts between the different anatomical sites of fixation surgery: distal humerus, radial head, and olecranon. Statistical significance was set at P < .05. The post-operative outcomes evaluated (SSI, hematoma formation, seroma, wound dehiscence, I&D , and blood transfusion) were prespecified clinical endpoints. Because these outcomes were defined a priori, formal correction for multiple comparisons was not applied. All analyses were conducted using R Studio version 2025.05.0 (Posit PBC, Boston, MA, USA).

Results

After application of inclusion and exclusion criteria, a total of 6,359 patients in the unmatched cohort and 3,479 patients in the matched cohort were included in the final analysis. Patients on SSRIs and SNRIs were older (52 vs. 45 year old; P < .001), more likely to be female (72.6% vs. 45.9%; P < .001), have diabetes (17.1% vs. 9.3%; P < .001), obesity (24.0% vs. 12.5%; P < .001), and use tobacco (18.8% vs. 14.5%; P < .001). Patients on SSRIs/SNRIs had an overall higher CCI profile (1.2 vs. 0.6 CCI score; P < .001; Table I) and had a higher distribution of radial head surgery (20.4% vs. 14.6%; P < .001). After propensity matching, age and sex had no significant differences between cohorts. However, there was still a significant difference in diabetes, obesity, and average CCI, though the effect sizes were closer (Table I). Furthermore, despite the statistical differences in comorbidities between the control and treatment cohorts, Figure 1 shows that the absolute SMDs between the cohorts were appropriately balanced for age, sex, diabetes, obesity, tobacco use, and CCI profile.

Table I.

SSRI and SNRI use by patient demographics and comorbidities: unmatched and matched cohorts.

Characteristic	Unmatched cohort			Matched cohort
	Elbow surgery + SSRI/SNRI	Elbow surgery - SSRI/SNRI	P value	Elbow surgery + SSRI/SNRI	Elbow surgery - SSRI/SNRI	P value
	N = 1,065	N = 5,294		N = 985	N = 2,494
Mean age, yr (SD)	51.9 (12.2)	44.7 (14.9)	<.001	51.1 (12.2)	50.2 (12.7)	.04
Sex (%)
Male	292 (27.4)	2,866 (54.1)	<.001	290 (29.4)	821 (32.9)	.06
Female	773 (72.6)	2,428 (45.9)		692 (70.5)	1,680 (67.1)
Procedure (%)			<.001			.05
Distal humerus	474 (44.5)	2,526 (47.7)		445 (45.2)	1,162 (46.6)
Olecranon	374 (35.1)	1,993 (37.6)		342 (34.7)	919 (36.8)
Radial head	217 (20.4)	775 (14.6)		198 (20.1)	413 (16.6)
Diabetes mellitus (%)	182 (17.1)	491 (9.3)	<.001	141 (14.3)	306 (12.3)	.10
Obesity (%)	256 (24.0)	660 (12.5)	<.001	205 (20.8)	414 (16.6)	.01
Tobacco use (%)	200 (18.8)	766 (14.5)	<.001	165 (16.7)	356 (14.3)	.06
MDD∗ (%)	619 (58.1)	466 (8.8)	<.001	561 (56.9)	250 (10.0)	<.001
Anxiety (%)	311 (29.2)	246 (4.6)	<.001	281 (28.5)	129 (5.2)	<.001
Atrial fibrillation (%)	41 (3.8)	114 (2.1)	.001	27 (2.7)	71 (2.8)	.86
Prior DVT/PE∗ (%)	13 (1.2)	23 (0.4)	.002	12 (1.2)	13 (0.6)	.03
Mean CCI∗ score (SD)	1.2 (1.8)	0.6 (1.2)	<.001	0.9 (1.4)	0.7 (1.3)	.001

SSRI, selective serotonin re-uptake inhibitor; SNRI, serotonin-norepinephrine re-uptake inhibitor; SD, standard deviation; MDD, major depressive disorder; DVT, deep vein thrombosis; PE, pulmonary embolism; CCI, Charlson Comorbidity Index.

Values are given as number of patients, with the percentage in parentheses, except for age and CCI, which is given as the mean and the standard deviation. Bold signifies a P-value <.05.

Figure 1.

Absolute mean differences for covariates included in propensity-score matching between unmatched and matched datasets. CCI, Charlson Comorbidity Index.

As seen in Table II, multivariable analyses for the unmatched cohorts revealed a significant difference in the odds of developing a post-operative SSI at both 30 days (3.5% vs. 2.7%; odds ratio [OR]: 1.6; P = .02) and 90 days (5.8% vs. 3.9%; OR: 1.6; P = .01) for patients on an SSRI/SNRI. This significant difference was also seen in the matched cohorts (Table III) at 30 days (3.4% vs. 2.2%; OR: 1.5; P = .04) and 90 days (5.4% vs. 3.3%; OR: 1.7; P = .01).

Table II.

Multivariable analyses of complications - SSRI and SNRI vs. No SSRI/SNRI – unmatched cohorts.

Characteristics	Elbow surgery + SSRI/SNRI	Elbow surgery - SSRI/SNRI	Odds ratio∗ (95% CI)	P value
	N = 1,065	N = 5,294
30-d complications (%)
Surgical Site Infection (SSI)	3.5	2.7	1.6 (1.1-2.4)	.02
Wound dehiscence	0.7	1.1	0.8 (0.3-1.7)	.49
Hematoma	0.7	0.9	1.0 (0.4-2.3)	.97
Seroma	0.3	0.1	2.1 (0.5-10.0)	.34
Incision and drainage (I&D)	0.7	0.8	0.9 (0.4-2.2)	.91
Blood transfusion	0.2	0.1	2.6 (0.4-16.5)	.32
90-d complications (%)
Surgical Site Infection (SSI)	5.8	3.9	1.6 (1.2-2.2)	.01
Wound dehiscence	1.6	1.6	1.1 (0.6-1.9)	.81
Hematoma	1.3	1.0	2.0 (1.0-3.7)	.03
Seroma	0.5	0.1	2.9 (0.9-9.6)	.09
Incision and drainage (I&D)	0.8	0.9	1.0 (0.5-2.2)	.99

SSRI, selective serotonin re-uptake inhibitor; SNRI, serotonin-norepinephrine re-uptake inhibitor; CI, confidence interval.

Bold signifies a P-value <.05.

^∗Values are given as the odds ratio for the SSRI/SNRI group, with the 95% CI in parentheses.

Table III.

Multivariable analyses of complications - SSRI and SNRI vs. no SSRI/SNRI – matched cohorts.

Characteristics	Elbow surgery + SSRI/SNRI	Elbow surgery - SSRI/SNRI	Odds ratio∗ (95% CI)	P value
	N = 985	N = 2,494
30-d Ccomplications (%)
Surgical Site Infection (SSI)	3.4	2.2	1.5 (1.0-2.4)	.04
Wound dehiscence	0.5	0.8	0.7 (0.3-1.8)	.44
Hematoma	0.6	0.5	1.3 (0.5-3.5)	.60
Seroma	0.3	0.2	1.8 (0.4-8.1)	.61
Incision and drainage (I&D)	0.6	0.7	0.9 (0.3-2.2)	.74
Blood transfusion	0.2	0.1	2.6 (0.4-18.9)	.34
90-d complications (%)
Surgical Site Infection (SSI)	5.4	3.3	1.7 (1.2-2.4)	.01
Wound dehiscence	1.0	1.4	0.7 (0.4-1.5)	.42
Hematoma	1.2	0.6	2.2 (1.0-4.7)	.04
Seroma	0.5	0.3	1.8 (0.6-5.8)	.31
Incision and drainage (I&D)	0.7	0.8	0.9 (0.4-2.1)	.81

SSRI, selective serotonin re-uptake inhibitor; SNRI, Serotonin-Norepinephrine Re-uptake Inhibitor; CI, confidence interval.

Bold signifies a P-value <.05.

^∗Values are given as the odds ratio for the SSRI/SNRI group, with the 95% CI in parentheses.

While there was no difference in the odds of developing a hematoma at 30 days regardless of matching, there was a difference in hematoma development at 90 days for both unmatched (1.3% vs. 1.0%; OR: 2.0; P = .03; Table II) and matched analyses (1.2% vs. 0.6%; OR: 2.2; P = .04; Table III). There was no difference in the odds of developing a wound dehiscence, seroma formation, need for I&D procedures, or blood transfusion requirements at either the 30- or 90-day time points in both the unmatched and matched cohorts. There was only 1 patient out of 7 from the SSRI/SNRI cohort who had a hematoma initially that subsequently developed an SSI within 90 days (14.3%). In the control group, there were 7 patients out of 44 who had an initial hematoma that later developed an SSI (15.9%).

The incidence of SSI following elbow fixation varied by primary anatomical location, with distal humerus fractures demonstrating the highest overall average rates regardless of SSRI/SNRI usage at both 30 days (3.2%) and 90 days (4.6%). This was followed by olecranon fractures (2.5% and 4.2%, respectively) and radial head fractures, which exhibited the lowest SSI rates at 30 days (2.1%) and 90 days (3.2%). As shown in the subgroup analysis from Table IV, when stratified by perioperative SSRI or SNRI use, patients undergoing olecranon fixation who were on these medications demonstrated significantly higher rates of SSI at both 30 days (5.3% vs. 2.0%, P = .01) and 90 days (8.8% vs. 3.4%, P = .01) compared with those not taking SSRIs/SNRIs. In contrast, no significant differences in SSI rates were observed for distal humerus or radial head fixation at either post-operative time point between patients on SSRI/SNRIs vs. those who were not.

Table IV.

Subgroup analysis: rates of 30-day and 90-day SSI grouped by SSRI/SNRI vs. no SSRI/SNRI and elbow fracture surgery.

Surgical procedure	30-d SSI		90-d SSI
	SSRI/SNRI	No SSRI/SNRI	SSRI/SNRI	No SSRI/SNRI
Distal humerus	3.4%	2.5%	4.8%	3.8%
Olecranon∗†	5.3%	2.0%	8.8%	3.4%
Radial head	2.3%	2.2%	5.1%	2.7%

SSRI, selective serotonin re-uptake inhibitor; SNRI, serotonin-norepinephrine re-uptake inhibitor; SSI, Surgical Site Infection.

^∗P = .01 at 30 d.

^†Indicates P = .01 at 90 d.

Discussion

Given that SSRIs and SNRIs are among the most prescribed medications worldwide,²² understanding their association with perioperative bleeding and complications in traumatic elbow surgery is essential for anticipating risks and optimizing patient outcomes. Our study suggests that SSRI/SNRI usage was associated with a significant increase in both 30- and 90-day infection rates and 90-day hematoma rates in both matched and unmatched analyses. This study addresses a previously unexplored area by examining the relationship between SSRI/SNRI use and post-operative bleeding risks across a broad spectrum of elbow fixation surgeries, providing insights into potential perioperative risk factors.

Our findings were consistent with current literature. For example, Adelstein et al¹ showed that the use of serotonergic antidepressants was associated with higher rates of hematoma following anterior cervical spine surgery. Ruggiero et al³² also showed increased rates of post-operative hematoma in patients following proximal femur fracture fixation. The biologic plausibility of these associations has been well supported. Platelets play a crucial role in hemostasis, requiring serotonin for activation and aggregation.^{4,15,19,26,30,31} They acquire serotonin from plasma via serotonin transporter proteins,¹⁵ which SSRIs and SNRIs mechanistically block, leading to significantly reduced serotonin levels within platelets and subsequently impairing platelet aggregation.¹⁵ One study showed that SSRIs can even reduce intraplatelet serotonin concentrations by up to 80%.²⁵

While the effect size in hematoma rates between our 2 study cohorts are relatively small, the cumulative evidence supports a consistent association between SSRI/SNRI impairment on perioperative hemostasis. Notably, however, this difference reached statistical significance only within the 90-day post-operative period and thus warrants cautious interpretation. Hematomas identified between 30 and 90 days may not reflect the same biological process as early post-operative bleeding, but rather delayed detection, ongoing symptoms, follow-up evaluation, or variability in coding within administrative datasets. While less likely, it may also be possible that this temporal pattern may also suggest delayed recognition, potentially related to post-operative immobilization in splints or casts following elbow fracture surgery,³⁷ though this remains speculative and should not be interpreted as true delayed hematoma formation. Nevertheless, these findings highlight the importance of maintaining vigilance for hematoma-related complications in this population, particularly among patients with complex fracture patterns, prolonged operative times, or significant comorbidities. Post-operative hematoma formation has been associated with several serious sequelae, including peri-implant infection^11,21 and neurovascular compromise due to uncontrolled expansion.^8,12,27 In addition, hematomas may contribute to delayed bone healing and hardware displacement, ultimately resulting in malunion, nonunion, and the need for revision surgery.^9,29,33

Our study also demonstrated an association between SSRI/SNRI use and increased rates of 30-day and 90-day SSI following elbow fracture surgery. This association is likely multifactorial. Prior literature has shown that psychiatric comorbidities are associated with increased infection rates,^2,13 potentially due to immune modulation^17,23 as well as differences in self-care or adherence to post-operative instructions.¹⁴ It is also possible that post-operative swelling or fluid collections may be variably coded as hematoma or infection in administrative datasets, contributing to differences in reported SSI rates. Hematoma formation has been proposed as a potential mediator of infection, as hematomas may serve as a nidus for bacterial growth.²¹ However, this relationship was not clearly supported in our cohort. Only a small proportion of patients with hematoma subsequently developed SSI, and the proportion was similar between cohorts. This suggests that the increased SSI rates observed among patients taking SSRIs/SNRIs may reflect diagnostic overlap, coding variability, or residual confounding rather than a sole biologic effect of SSRI/SNRI use. While future research is needed to understand the association between SSRIs/SNRIs and infection rates, it is important for both orthopedic surgeons and patients to be aware of the observed correlation. As a result, surgeons may need to schedule closer follow-up with patients.

Interestingly, there was no difference in I&D requirements or blood transfusions between the 2 cohorts. Prior studies in hip, knee, and spine surgery have reported increased transfusion and reoperation rates among patients taking serotonergic antidepressants.^1,28 However, elbow surgery generally involves smaller operative fields and lower blood loss compared with larger orthopedic procedures. In addition, post-operative hematomas in the elbow may often resolve with conservative management or aspiration rather than requiring operative evacuation.³⁹

When stratified by surgical location, surgical fixation of the olecranon was associated with higher rates of 30-and 90-day SSI for patients on SSRIs/SNRIs, whereas those with fractures of the radial head or distal humerus showed no statistical difference in infection rates. This may be due to the anatomic positioning of the olecranon, which has relatively less overlying skin and soft-tissue coverage comparatively.³ This predisposes the region to a higher likelihood of damage to the surrounding skin, associated soft-tissue pressure necrosis, and subsequent infection, though future prospective studies would be needed to fully delineate this subgroup analysis.

There are several limitations to this study. First, the retrospective observational design allows for identification of associations but does not permit causal inference between SSRI/SNRI use and post-operative complications. In addition, there is the possibility of selection bias and confounding. Although propensity score matching was used to account for measured confounders, unmeasured variables may still influence outcomes. Patients prescribed SSRIs or SNRIs may differ systematically from those not receiving these medications in ways not fully captured by claims data. Factors such as psychiatric disease severity, alcohol use, frailty, nutritional status, health care utilization, and adherence to post-operative care may independently affect complication risk and detection. Although major depressive disorder and anxiety were included as baseline variables and adjusted for in regression analyses, these diagnoses may not fully reflect the severity or chronicity of psychiatric illness. As such, SSRI/SNRI use may serve as a proxy for underlying patient characteristics rather than a direct driver of post-operative complications. In addition, while propensity score matching aimed to create balanced cohorts, residual differences in certain comorbidities remained, as shown in Table I, which may have influenced outcomes.

Importantly, aspirin use could not be reliably excluded, as it is available over the counter and not consistently captured in prescription claims data, introducing potential residual confounding related to unmeasured antiplatelet use. Furthermore, claims data lack detailed clinical metrics such as hemoglobin levels or platelet function, which may provide additional context for bleeding risk.

Finally, multiple post-operative outcomes were evaluated across different time points and analytic models, which increases the risk of Type I error. Although these outcomes were prespecified and a formal correction for multiple comparisons was not applied, some statistically significant findings, particularly those with marginal P values, may represent spurious associations. These results should therefore be interpreted with caution.

A second limitation is that the reliance on commercial-claims data poses inherent challenges. Our study may have an underrepresentation of patients who were on Medicare, Medicaid, or were uninsured, creating a possible selection bias in the results. Diagnosis and procedure coding (ICD/CPT) may be inaccurate or incomplete. Hematoma formation, for instance, may be underreported unless severe enough to require clinical evaluation. Furthermore, at an early post-operative period, hematoma formation may potentially present similarly to an SSI, leading to disproportionately higher numbers of SSI being diagnosed rather than a hematoma. Similarly, medication claims do not confirm patient adherence; some patients may not have taken their prescribed SSRIs or SNRIs.

Third, the database does not provide sufficient granularity to reliably evaluate individual SSRI or SNRI agents or assess medication dosing. As a result, we were unable to determine whether specific medications or potential dose–response relationships influence post-operative bleeding or infection risk. Because of this, the potential differences in bleeding or infection risk among fluoxetine, sertraline, duloxetine, and other agents remain unexplored.

Conclusion

In this retrospective claims-based analysis, preo-perative SSRI/SNRI use was associated with higher odds of 90-day hematoma formation and SSI following elbow fracture surgery. These findings are consistent with existing biologic and clinical evidence suggesting a relationship between serotonergic medications and perioperative bleeding risk. While the observational design and potential for residual confounding warrant cautious interpretation, this study contributes to a growing body of literature on perioperative risk associated with SSRI/SNRI use. In addition to utilizing intraoperative techniques that promote effective local hemostasis, orthopedic surgeons should ensure closer follow-up of these patients and educate them about the potential increased risks suggested by our findings. Further prospective studies are needed to better understand this phenomenon and guide perioperative management of patients on SSRIs or SNRIs to optimize patient outcomes.

Disclaimers:

Funding: No funding was disclosed by the authors.

Conflicts of interest: The authors, their immediate families, and any research foundations with which they are affiliated have not received any financial payments or other benefits from any commercial entity related to the subject of this article.