Can You Donate a Kidney if You Take Antidepressants
Transpl Int. Author manuscript; bachelor in PMC 2022 January 16.
Published in concluding edited course equally:
PMCID: PMC6334638
NIHMSID: NIHMS890796
Antidepressant Medication Use Before and After Kidney Transplant: Implications for Outcomes
Krista L. Lentine
aEye for Abdominal Transplantation, Saint Louis Academy Schoolhouse of Medicine, St. Louis, MO, USA
bDivision of Nephrology, Section of Medicine, Saint Louis University School of Medicine, St. Louis, MO, USA
Abhijit S Naik
cSectionalization of Nephrology, Department of Medicine, Academy of Michigan, Ann Arbor, MI
Rosemary Ouseph
aCenter for Intestinal Transplantation, Saint Louis University Schoolhouse of Medicine, St. Louis, MO, USA
bDivision of Nephrology, Department of Medicine, Saint Louis University School of Medicine, St. Louis, MO, USA
Zidong Zhang
aMiddle for Abdominal Transplantation, Saint Louis University Schoolhouse of Medicine, St. Louis, MO, USA
David A. Axelrod
dPartitioning of Intestinal Transplantation, Department of Surgery, Brody Schoolhouse of Medicine, Greenville, NC, USA
Dorry 50. Segev
eSectionalization of Transplantation, Department of Surgery, Johns Hopkins Schoolhouse of Medicine, Baltimore, Doctor, U.s.
Vikas R. Dharnidharka
fTransplant Nephrology, Washington University Schoolhouse of Medicine, St. Louis, MO, The states
Daniel C. Brennan
fTransplant Nephrology, Washington Academy School of Medicine, St. Louis, MO, USA
Henry Randall
aCenter for Intestinal Transplantation, Saint Louis University Schoolhouse of Medicine, St. Louis, MO, U.s.a.
Raj Gadi
bDivision of Nephrology, Department of Medicine, Saint Louis University School of Medicine, St. Louis, MO, The states
Ngan North. Lam
1000Division of Nephrology, Academy of Alberta, Edmonton, AB, Canada
Gregory P. Hess
hSymphony Wellness, Conshohocken, PA, Usa
iLeonard Davis Plant for Wellness Economics, Academy of Pennsylvania, Philadelphia PA, USA
Bertram L. Kasiske
jPartitioning of Nephrology, Hennepin County Medical Center, Minneapolis, MN, The states
Marking A. Schnitzler
aCenter for Abdominal Transplantation, Saint Louis University School of Medicine, St. Louis, MO, USA
Abstract
Nosotros examined a novel database wherein national U.S. transplant registry identifiers were linked to records from a large pharmaceutical claims warehouse (2008 to 2015) to characterize antidepressant use before and later kidney transplantation, and associations (adjusted gamble ratio, aHR, 95% CI) with death and graft failure. Amid 72,054 recipients, 12.vi% filled antidepressant medications in the year before transplant, and use was more than common among women and patients who were white, unemployed, and had limited functional status. Pre-transplant antidepressant use was associated with 39% higher one-year bloodshed (aHR 1.39, 95% CI 1.xviii–1.64) and fifteen% higher all-cause graft loss adventure (aHR ane.15, 95% CI 1.02–one.30). More than 50% of patients who filled antidepressants pre-transplant connected apply mail-transplant. Antidepressant employ in the showtime year after transplant was associated with 2-fold higher risk of death (aHR 1.94, 95% CI 1.sixty–2.35), 38% college take a chance of decease-censored graft failure, and 61% college risk of all-cause graft failure risk in the subsequent twelvemonth. Pre-listing antidepressant use was likewise associated with increased mortality, but transplantation conferred a survival benefit regardless of pre-listing antidepressant use condition. While associations may in part reflect underlying behaviors or comorbidities, kidney transplant candidates and recipients treated with antidepressant medications should be monitored and supported to reduce the risk of adverse outcomes.
Keywords: Antidepressants, Kidney transplantation, Mortality, Pharmacy records, Registries
INTRODUCTION
Transplant candidates undergo thorough evaluation to assess suitability for transplant. Psychosocial considerations include pre-existing mental health conditions, social support, and adherence history.(i) Depression is a common mental health status, estimated to affect approximately nine% of Americans at whatever given time and ultimately 16% of the U.S. population over a lifetime.(2) The prevalence of depression is higher among patients with chronic illnesses, including chronic kidney disease.(2) Although kidney transplant has been shown to better quantity and quality of life compared with long-term dialysis,(iii) the implications of depression for kidney transplant-related outcomes are incompletely defined.
Prior studies have examined the prevalence, correlates, and outcomes associated with depression in transplant recipients, typically based on administration of survey instruments at unmarried centers. For example, 2 studies reported lower depression rates after transplant compared with rates among patients on the waiting list.(four,5) Correlates of depression among waitlisted candidates and transplant recipients have besides been described.(four–vi) One report of billing claims amidst Medicare-insured kidney transplant recipients found that depression diagnoses were more common amidst recipients who were women, white, diabetic, and those with prolonged dialysis durations.(7) A diagnosis of depression in the showtime 3 years after transplant was associated with increased risk of graft failure and expiry with a functioning graft. College rates of post-transplant death in depressed patients have besides been reported in single-center cohort studies.(8, 9)
Currently, the national U.S. transplant registry does not collect measures of mental health comorbidity or treatments earlier or later on transplant. However, linking the transplant registry with other data sources tin can combine the value of transplant recipient status, baseline clinical characteristics, and patient and graft survival records with additional outcome and exposure information. Chemist's shop fill records offer non-obtrusive measures of prescribed health care that may serve as surrogate measures of comorbidity.(10–13) For mental health atmospheric condition such equally low, prescription data tin can identify patients with medically treated forms of the disorder.
We examined the frequency, correlates, and outcomes of antidepressant medication utilise as a measure of treated depression in a national sample identified by linking the transplant registry with chemist's shop fill records. Using this integrated data source, we assessed associations of pre-transplant and pre-listing antidepressant use with death and graft loss, persistence of pre-transplant antidepressant employ patterns after transplant, and associations of antidepressant apply in the first year post-transplant with subsequent agin events.
METHODS
Information Sources
This report used data from the Scientific Registry of Transplant Recipients (SRTR). The SRTR system includes data on all transplant candidates, recipients and donors in the United states of america, submitted by the members of the Organ Procurement and Transplantation Network (OPTN). The Health Resources and Services Administration (HRSA), US Section of Wellness and Human Services, provides oversight of the activities of the OPTN and SRTR contractors. Baseline demographic data ascertained for kidney transplant recipients at the time of transplant included historic period, sex, and race as reported by the transplant center.
Pharmacy fill data were assembled past linking SRTR records for kidney transplant recipients with billing claims from Symphony Health Solutions (SHS), a large US pharmaceutical claims data warehouse that collects prescription drug fill records including self-paid fills and those reimbursed past private and public payers. SHS comprises National Council for Prescription Drug Program format prescription claims aggregated from multiple sources including claims warehouses, retail pharmacies, and prescription benefit managers for approximately lx% of US retail chemist's transactions. Individual claim records include the engagement of a given pharmacy make full with the national drug code identifying agent and dosage. Subsequently Institutional Review Board and HRSA approvals, SHS records were linked with SRTR records for kidney transplant recipients. A deterministic de-identification strategy was applied, wherein patient identifiers (last name, first proper noun, date of birth, sex activity, and ZIP code of residence) were transformed before delivery to the Saint Louis Academy researchers with Health Data Portability and Accountability Act and HITECH-certified encryption engineering from SHS. The patient de-identification software employs multiple encryption algorithms in succession to guarantee that the resulting "token" containing encrypted patient identifiers can never exist decrypted. Notwithstanding, the algorithm yields the same results for a given ready of information elements, such that linkages by unique anonymous tokens are possible.
Sampling and Exposure Definitions
Patients selected for the primary assay had SRTR records of kidney transplantation, underwent transplant betwixt January 2008 and January 2015, and had at least ane twelvemonth of available pharmaceutical make full records before transplant. Patient clinical and demographic characteristics, likewise characteristics of the donated organ and other transplant factors, were defined by the OPTN Transplant Candidate and Recipient Registration forms (Tabular array ane). The chief exposure of interest was chemist's claims for antidepressant medications in the twelvemonth before transplant, including Selective Serotonin Reuptake Inhibitors (SSRI), tricyclic antidepressants, newer generation antidepressants, and combination pills (SDC, Tabular array one). Medications primarily indicated for bipolar disorder, such as lithium, were not included. Nosotros also quantified the months that antidepressants were dispensed to patients in the 12 calendar month period before transplant, amongst those with a least 12-months of pre-transplant chemist's shop records, every bit a metric of the intensity of exposure.(14–17) To account for concomitant employ of multiple agents, the exposure metric for any antidepressant exposure aggregated fill days from different classes even if prescription dates were over-lapping.(14–17) Split analyses quantified antidepressant apply in the year earlier waitlisting and in the first year afterwards transplantation.
Table i.
Distributions of clinical traits in the written report sample co-ordinate to pretransplant antidepressant employ level, and propensity of using antidepressants before and after transplant.
| Traits by Pretransplant Use | Propensity Model Associations | |||
|---|---|---|---|---|
| No Use (N=62974) | Some Employ (Due north=9080) | Pretransplant use | Posttransplant Employ | |
| % | % | Adapted Odds Ratio (95% CI) | Adjusted Odds Ratio (95% CI) | |
| Recipient Factors | ||||
| Age, yrs. | ‡ | |||
| <eighteen | 5.1 | 2.five | 0.32 (0.25–0.41) ‡ | 0.57 (0.44–0.73) ‡ |
| xviii to xxx | 7.7 | 10.three | Reference | Reference |
| 31 to 45 | xix.5 | 21.3 | 0.91 (0.81–1.02) | 1.04 (0.91–1.20) |
| 46 to 60 | 36.half-dozen | 38.0 | 0.83 (0.74–0.93) † | one.00 (0.87–1.14) |
| >60 | 31.2 | 27.9 | 0.63 (0.56–0.71) ‡ | 0.89 (0.77–one.02) |
| Female | 38.8 | 43.vii‡ | 1.23 (one.16–ane.31) ‡ | 1.xxx (i.21–1.40) ‡ |
| Recipient Race | ‡ | |||
| White | 52.5 | 61.2 | 1.59 (one.47–1.73) ‡ | 1.47 (1.34–one.61) ‡ |
| Black | 26.seven | 21.0 | Reference | Reference |
| Hispanic | xiv.ane | 13.half-dozen | 1.21 (1.09–1.34) † | 1.00 (0.88–1.13) |
| Other | 6.vii | 4.3 | 0.82 (0.lxx–0.96) * | 0.66 (0.55–0.80) ‡ |
| Body mass index, kg/m2 | * | |||
| <18.5 | 4.2 | 3.three | one.01 (0.84–1.21) | 0.82 (0.66–1.01) |
| xviii.5 to 25 | 28.7 | 28.5 | Reference | Reference |
| 25 to 30 | 31.v | 31.iv | 1.02 (0.94–1.ten) | 0.97 (0.89–1.06) |
| >thirty | 33.2 | 33.9 | ane.00 (0.92–ane.08) | ane.01 (0.93–1.ten) |
| Missing | 2.5 | 3.0 | ane.23 (1.02–1.48) * | 0.99 (0.81–1.22) |
| Cause of ESRD | ‡ | |||
| Diabetes | 23.4 | 25.8 | 1.ten (0.95–1.26) | i.07 (0.91–1.26) |
| Glomerulonephritis | 23.1 | 25.5 | 1.10 (one.00–one.21) | 0.98 (0.88–1.09) |
| Hypertension | 25.five | 21.eight | 0.92 (0.83–ane.02) | 0.90 (0.80–1.01) |
| Polycystic kidney affliction | nine.9 | 9.4 | 0.97 (0.86–ane.10) | 1.00 (0.87–1.14) |
| Other | xviii.i | 17.5 | Reference | Reference |
| ESRD duration, mos. | ‡ | |||
| None (pre-emptive) | xviii.0 | 12.seven | 0.59 (0.53–0.65) ‡ | 0.95 (0.86–1.05) |
| >0 to 24 | 29.iii | 36.vii | Reference | Reference |
| 25 to 60 | 31.1 | 32.4 | 0.82 (0.76–0.88) ‡ | 0.96 (0.87–1.05) |
| >60 | twenty.8 | 17.five | 0.68 (0.62–0.75) ‡ | 1.05 (0.94–ane.17) |
| Missing | 0.8 | 0.vii | 0.70 (0.50–1.00) * | 1.21 (0.88–ane.66) |
| Recipient comorbidities | ||||
| Diabetes | 32.0 | 34.1* | 1.03 (0.92–1.15) | 1.05 (0.93–1.xx) |
| Coronary disease/angina | five.7 | half-dozen.v* | 1.05 (0.97–ane.14) | one.00 (0.92,1.10) |
| COPD | 1.2 | one.seven† | i.07 (0.89–one.29) | ane.01 (0.81–1.24) |
| Hypertension | 78.four | 78.seven | 0.92 (0.78–1.08) | 1.08 (0.ninety,ane.29) |
| Cognitive vascular disease | 2.3 | 2.seven | one.32 (one.05–1.67) * | 0.99 (0.72,1.35) |
| Peripheral vascular disease | iii.4 | 3.seven | i.09 (0.96–1.23) | 1.01 (0.88,1.17) |
| Highest Level of Education | † | |||
| College/Graduate School | 47.1 | 45.vii | Reference | Reference |
| High School or lower | 43.7 | 46.3 | one.09(one.02–one.17) * | 1.08 (1.00–1.16) * |
| Unknown | 9.1 | eight.0 | 0.96(0.85–one.08) | 0.94 (0.83–1.07) |
| Employment Status | ‡ | |||
| Working | 30.3 | 24.9 | Reference | Reference |
| Not Working | 57.4 | 64.half-dozen | 1.40 (i.29–1.51) ‡ | one.18 (one.08–1.28) † |
| Unknown | 12.3 | 10.5 | 1.39 (i.23–1.57) ‡ | 1.16 (i.01–one.33) * |
| Recipient physical capacity | ‡ | |||
| No Limit | 65.0 | 63.5 | Reference | Reference |
| Limited | half dozen.half dozen | 9.0 | one.25 (ane.12–ane.39) ‡ | 1.14 (1.01–one.thirty) * |
| Unknown | 28.five | 27.v | 1.08 (one.00–i.16) * | 0.98 (0.91–1.07) |
| Insurance Type | † | |||
| Individual | 36.0 | 33.7 | Reference | Reference |
| Public | 64.0 | 66.iii | 0.90(0.83–0.97) * | 0.98 (0.xc–ane.07) |
| Previous transplant | xiii.5 | 14.8* | Not applicable to pretransplant use | 0.87 (0.78–0.97) * |
| PRA level (nearly recent) | † | |||
| < 10 | 69.iii | 67.four | Reference | |
| ten to 79 | 18.4 | 18.7 | one.07 (0.98–ane.17) | |
| ≥80 | half-dozen.7 | 8.2 | ane.04 (0.90–one.twenty) | |
| Missing | 5.7 | 5.7 | 0.91 (0.76–i.10) | |
| Transplant & Donor Factors | ||||
| HLA mismatches | * | |||
| Zippo A, B, and DR | 7.8 | 9.2 | 1.03 (0.92–1.xvi) | |
| Nothing DR | xi.3 | xi.iii | one.02 (0.91–1.thirteen) | |
| Other | lxxx.nine | 79.v | Reference | |
| Donor Type | * | |||
| Living | 36.0 | 38.4 | 1.03 (0.94–one.12) | |
| Standard Criteria Deceased | 44.6 | 42.ix | Reference | |
| Expanded Criteria Deceased | 9.4 | 8.9 | one.02 (0.90–1.sixteen) | |
| Donation after Cardiac Expiry | x.0 | ix.8 | 1.21 (1.07–1.36) † | |
| Twelvemonth of transplant | ‡ | |||
| 2007–2009 | 19.5 | 22.6 | Reference | Reference |
| 2010–2012 | 46.4 | 47.viii | 0.90 (0.84–0.97) * | 0.74 (0.69–0.79) ‡ |
| 2013–2015 | 34.0 | 29.6 | 0.77 (0.71–0.84) ‡ | 0.lxx (0.63–0.77) ‡ |
Decease and Graft Failure
Mortality was defined as death from any crusade. Graft failure was defined as return to maintenance dialysis or "pre-emptive" re-transplantation. All-crusade graft failure included graft loss due to patient death. Ascertainment time for outcomes in the kickoff-twelvemonth post-transplant was censored at day 365 after transplantation or study end (Jan 31, 2015). To appraise the implications of antidepressant use in the showtime year of transplant, we examined clinical outcomes from >1 to two years post-transplant or terminate of written report. Finally, to frame post-transplant outcomes in the context of survival on the waiting list, we examined associations of pre-listing antidepressant employ with death after list, censored at transplantation.
Statistical Analyses
Datasets were merged and analyzed with SAS (Statistical Analysis Software) version 9.4 (SAS Institute Inc., Cary, NC). Distributions of clinical and demographic traits amid recipients with each level of antidepressant exposure, compared with no antidepressant utilise, were compared by the χ2 test. Propensity models for the likelihood of whatever antidepressant utilize in the pre-transplant menses and the starting time year post-transplant were synthetic past multivariable logistic regression.(10, 11)
The log-rank examination was used to assess the statistical significance of differences in unadjusted incidence of patient death and graft loss according to pre-transplant antidepressant use, and differences in these outcomes after the first transplant anniversary co-ordinate to first year antidepressant utilise. Adjusted associations of antidepressant utilise with graft failure and death (adjusted hazards ratio, aHR) were quantified by multivariable Cox regression including adjustment for recipient, donor, and transplant clinical factors as listed in Table one. Outcome models were also stratified by quintile of propensity for pre-transplant antidepressant use as previously described in like studies of medication use and post-transplant outcomes, to minimize the effect of confounding by indication.(x, 11) Nosotros also examined associations of transplantation with death on the waitlist among those who did and did not fill antidepressants before listing past modeling transplant as a time-varying predictor of post-list mortality, including adjustment for baseline candidate demographic and clinical traits.
RESULTS
Clinical Correlates of Antidepressant Use Before and After Transplant
Between January 2008 and Jan 2015, 80,849 developed recipients of kidney-merely transplants were recorded in the SRTR database. Of these, 72,054 had linked pharmacy claims 1-twelvemonth before transplant. Among the eligible sample, 12.6% filled an antidepressant in the year before transplant; distribution of elapsing of use was: <two months, n=3,026; 2 to 5 months, n=iii,186; >5 months, due north=2,868. The almost common class of antidepressant filled before transplant was SSRIs (61.7%), followed by newer-generation antidepressants (25.3%) and tricyclic antidepressant therapy (12.9%); combination therapies accounted for only 0.1% of overall utilise.
Distributions of baseline clinical traits according to pre-transplant antidepressant use are shown in Table 1. Compared with transplant recipients who did not make full antidepressants before transplant, those who used antidepressants were more unremarkably aged xviii–30 years, women, white, unemployed, accept limited functional capacity, and were more than probable to have chronic obstructive pulmonary disease (COPD). Considered in terms of any fills and adjusted for other baseline factors, pre-transplant antidepressant use was 59% more than likely among white versus black patients (adapted odds ratio (OR), i.59, 95% CI 1.47–1.73), 22% more than likely among women than among men (aOR 1.23, 95% CI 1.16 –1.31), and xl% more than likely among unemployed than among employed recipients (aOR 1.40, 95% CI 1.29–1.51) (Table 1). Recipients who filled antidepressants before transplant were less likely to undergo preemptive transplant, and antidepressant use declined amid transplant recipients in more recent years. Similarly, the strongest correlates of antidepressant use in the twelvemonth afterward transplant were white race (aOR 1.47, 95% CI 1.34–ane.61) and female sex (aOR 1.30, 95% CI 1.21–1.twoscore); other patterns for utilise in the yr after transplant were like only attenuated compared with associations with pre-transplant antidepressant employ (Tabular array 1).
Patient and Graft Survival Co-ordinate to Antidepressant Medication Utilize
Over the first year post-transplant, unadjusted patient death was higher for recipients who used antidepressants in the year before transplant than for those who did not (two.5% vs 3.5%; P< 0.0001) (Figure 1). After multivariate adjustment for recipient, donor, and transplant factors, and for propensity for the likelihood of pre-transplant antidepressant fills (Tabular array one), recipients who filled antidepressants in the year earlier transplant had 39% higher adventure of death (aHR ane.39, 95% CI 1.18–1.64) over the outset yr than non-users ( Figure ii; SDC, Table 2). Pre-transplant antidepressant utilise was likewise independently associated with increased hazard of all-cause graft loss (aHR 1.15, 95% CI one.02–1.30), although the association was driven by death, and antidepressant medication use before transplant was not associated with death-censored graft failure over the kickoff yr (aHR 0.97, 95% CI 0.82–one.15). Outcomes did not differ according to course of antidepressant medication, or with duration.
. Death and graft failure according to antidepressant apply before and after kidney transplant. P-values: * p<0.05–0.002; † p=0.00 –0.0001; ‡ p<0.0001, for differences in 1yr outcomes in those who filled antidepressants compared to no use. ACGF, all-cause graft failure; DCGF, decease-censored graft failure; KTx, kidney transplant
Adjusted associations of antidepressant use before and after kidney transplant with subsequent death and graft failure. Adjusted for recipient, donor, and transplant clinical factors equally listed in Tabular array 1 (SDC, Table 3). ACGF, all-crusade graft failure; DCGF, death-censored graft failure; KTx, kidney transplant
Patient decease (3.four% vs. one.7%; P <0.0001), death-censored graft failure (2.5% vs. 1.9%; P = 0.0006), and all-cause graft loss (5.iii% vs. iii.ii%; P <0.0001) from year one to 2 were all higher amid patients who filled antidepressants in the year after transplant than for non-users ( Figure 1). After multivariate and propensity adjustment, antidepressant apply in the first year subsequently transplant was associated with well-nigh twice the risk of death (aHR one.94, 9%% CI 1.lx–2.35), 36% higher death-censored graft failure risk (aHR i.36, one.08–one.lxx), and 61% college all-cause graft failure hazard (aHR ane.60, 95% CI ane.37–1.88) ( Figure two; SDC, Table iii).
Among candidates with 1-year of prelisting chemist's make full records, 12% filled antidepressants in the twelvemonth earlier list. Similar to the associations of anti-depressant utilize with post-transplant expiry risk, compared to those who did non fill up antidepressants, patients who used antidepressants in the twelvemonth earlier list had college rates of 1-yr transplant-censored bloodshed (aHR 1.65, 95% CI 1.48 –1.76). Importantly, transplantation was associated with approximately 60% reductions in the risk death after listing among patients who filled antidepressants before listing (aHR 0.42, 95% CI 0.38–0.46) as among those without prelisting antidepressant medication fills (aHR 0.43, 95% CI 0.41–0.45). We did not observe interactions between antidepressant utilize and baseline factors on study outcomes.
Antidepressant Use Patterns Before and Later Transplant
To assess the persistence of pre-transplant antidepressant use patterns postal service-transplant, we examined a subgroup of recipients with chemist's shop database activeness extending from i twelvemonth pre-transplant to 1 twelvemonth post-transplant (north=64,453). Overall, 51.8% of patients who filled an antidepressant therapy pre-transplant connected to use post-transplant, while thirteen.2% of patients with no history of antidepressant medication use initiated antidepressant therapy in the offset yr post-transplant (Figure iii).
Mail-transplant antidepressant filling patterns co-ordinate to pre-transplant antidepressant use.
A graded blueprint of antidepressant use was noted based on the elapsing of pre-transplant utilize. Recipients with more than than v months of pre-transplant antidepressant use continued to use antidepressants mail-transplant; 58.4% filled for more than v months and only 20.9% filled none in this period (Effigy 4). In contrast, only 7.three% of recipients who did not use antidepressants pre-transplant used for more than 5 months in the starting time yr mail service-transplant; ii.five% filled for ii–5 months, and three.4% for less than 2 months. Clinical correlates of new antidepressant initiation after transplant included factors associated with pre-transplant use such as female sex, white race, diabetes, COPD, lower teaching level, unemployment, and limited functional condition. Additional factors associated with new initiation of antidepressant therapy after transplant included obesity, coronary avenue illness, cerebrovascular disease, previous transplant, and, in contrast to any pre-transplant use, more recent year of transplant (SDC, Table four).
DISCUSSION
We examined a linkage of national transplant registry information with outpatient prescription fill records from a pharmaceutical claims warehouse to examined apply of antidepressant medications before and after kidney transplantation, and observed several key findings. 1) Overall, 12.half dozen% of recipients filled antidepressant medications in the twelvemonth before transplant, and employ was more mutual among recipients who were women, white, unemployed, and those with limited functional condition. 2) More than l% of patients who filled antidepressants pre-transplant connected use after transplant, and continued use was more common among those with more sustained pre-transplant antidepressant employ. 3) Xiii percent of recipients who did not utilise antidepressants before transplant initiated treatment in the first year later transplant. Correlates of new antidepressant initiation too included obesity, coronary avenue disease, cerebrovascular disease, and previous transplantation. 4) Pre-transplant antidepressant use was associated with 40% higher adjusted bloodshed risk and twenty% higher all-cause graft loss take a chance in the showtime year after transplant. v) Antidepressant use in the first yr later on transplantation had of import prognostic implications, predicting twice the take chances of death, 38% higher decease-censored graft failure risk, and 61% higher all-cause graft loss hazard over the next year compared to no use. six) Pre-listing antidepressant use was also associated with increased mortality compared to no use, but transplantation conferred a survival benefit regardless of pre-listing antidepressant use status.
Prior studies have examined the prevalence of depression among samples of transplant recipients defined by cocky-reported symptoms using assessment scales such every bit the Brook Depression Inventory, the Hospital Anxiety and Depression Scale (HADS), the Center for Epidemiologic Studies Depression Scale (CES-D), the Zung Self Rating Depression Scale, and the Taiwanese Depression Questionnaire.(iv, v, 9, 18–22) These studies differ in sampling and design, and were performed in diverse locations including Turkey, Iran, Hungary, Taiwan, Japan, kingdom of the netherlands, and the United Kingdom every bit well every bit the United States. A recent meta-analysis of studies from 2004 to 2022 included six studies (iv cross-sectional, ii instance-control) found that low symptoms among transplant recipients ranged from fourteen.8% to 41%, just rates were consistently lower than in dialysis patients.(23) Our design differs in examining medication-treated low, a measure that requires a patient to report symptoms to a care provider and take pharmacotherapy. Dobbels et al. used billing claims, a study measure that besides requires patients to come up to clinical attention for depressive symptoms, to identify depression in Medicare-insured Usa kidney transplant recipients (1995–2003), and identified depression diagnoses in 5% by 1 year post-transplant.(seven) Administrative data including pharmacy fill records offering an additional perspective on transplant-related mental health outcomes diagnosed in existent practise that can complement and extend observations obtained through surveys, interviews, and case reports in smaller samples. In interpreting our results, however, it is important to note that antidepressant medications may exist used for other conditions including anxiety, obsessive compulsive disorders and neuropathic pain, or off-label uses.
Consistent with prior studies,(seven) nosotros plant that female person transplant recipients more commonly received pharmacotherapy for depression than male recipients. Gender-based variation in the frequency of reported depression is well established in the general population. For example, a nationally representative face-to-face household survey in 48 states estimated that the lifetime odds of low for American women are one.7-times the odds for men (95% CI one.5–2.0).(24) Nosotros previously observed that depression diagnoses were more than twice as mutual in female than in male living kidney donors, and that this pattern was consistent among not-donor beneficiaries of the same insurer.(25) In the current study, women were more likely to fill antidepressant medications earlier transplant and in the year later transplant, and were 70% more than likely than men to start new antidepressant therapy after transplant.
We also constitute that white recipients were more likely to fill antidepressant medications before transplant and after transplant, and were more than twice every bit likely every bit African Americans to outset new antidepressant therapy after transplant. Significantly lower lifetime prevalence of major depressive disorder was identified among African Americans (adapted odds ratio 0.51) and Hispanics (adapted odds ratio 0.38) compared with white participants in the National Health and Nutrition Examination Survey (NHANES) III.(26) The machinery of lower frequencies of clinically detected depression among persons of not-white racial and ethnic backgrounds appears to be in part due to reluctance on the part of members of minority groups to seek mental wellness intendance and indirect, or "culture jump." presentations. An investigation of the symptomatology of depressed Chinese Americans plant that 42% of those with major low initially presented with concrete complaints, while none reported complaints of mood alteration.(27) Manifestation of depression with somatic, rather than mental or emotional, symptoms has been identified in Hispanic and Asian Indian populations.(28, 29) Reduced admission to adequate treatment for acute depression, defined past specialty provider encounters and use of antidepressant therapy, has been reported among African Americans and Asians with depression.(xxx) Notably, transplant recipients receive illness-specific Medicare entitlement for the kickoff 3 years post-transplant and have regular follow-up visits under monitoring protocols, supporting that access barriers are non the primary determinant of racial differences in low intendance afterwards transplant. Future inquiry should investigate whether demographic differences in measures of depression, including utilize of antidepressant medications, reverberate care seeking, clinical observation, or true differences in disease burden.
We also found that use of antidepressant therapy before transplant was independently associated with increased take a chance of death and graft loss in the first year later on transplant, and that recipients who filled antidepressants in the first yr after transplant had almost twice the take a chance of subsequent death and 38% higher death-censored graft failure risk compared with those who did not crave antidepressants. These observations are consistent with a study of 527 kidney transplant recipients in the netherlands that identified associations of depression divers by a symptom checklist with twice the risk of cardiovascular and all-cause mortality over an average of 7 years of follow-upwardly.(nine) Similarly, in a cohort of 840 kidney transplant recipients in Republic of hungary, bloodshed was higher among those with versus without depressive symptoms defined by the CES-D scale (21% vs. thirteen% over a mean 58 months).(8) Symptoms of depression may be a manifestation of underlying medical weather condition, and depression has been implicated equally a risk factor for mortality among patients with a diverseness of chronic health conditions including heart failure,(31) coronary artery illness,(32) rheumatoid arthritis,(33) lupus,(34) COPD,(35) and diabetes,(36) among others. While the association of depression with mortality may reflect confounding from other comorbid atmospheric condition, various causal mechanisms take also been proposed. Patients who are depressed may take increased non-adherence,(37, 38) less physical activeness, poor eating habits, or substance use behaviors including smoking and alcohol employ.(39) Other proposed bio-behavioral mechanisms include autonomic dysregulation,(twoscore) increased platelet aggregation,(41) underlying inflammation,(42) and fifty-fifty reduced cellular immunity.(43) For transplant recipients, compliance with medical care is of particular concern and includes the demand to attach to immunosuppression therapy and other transplant-related medications, perform regular lab testing, and attend follow-up appointments.(44, 45) Non-adherence among transplant recipients is often difficult to diagnose, but when recognized, has been shown to correlate strongly with preventable allograft loss and poor patient outcomes.(46, 47) Future studies should examine possible connections betwixt measures of low including pharmacological treatment, care adherence, other behaviors including substance use, and outcomes amid transplant recipients.
Regardless of the mechanisms of association, identification of novel markers of mail-transplant outcomes is timely and can help transplant programs assess and manage risk at a programmatic level. Transplantation in the US is an increasingly regulated field with a high level of public reporting. Transplant centers are graded for recipient and graft survival using risk-adjusted equations adult by SRTR to predict expected 1-year and three-yr postal service-transplant patient and graft survival.(48) Importantly, SRTR equations practise non adjust for mental health atmospheric condition or medication use history as hazard factors for post-transplant death or graft loss. Thus, centers performing transplants in patients who require antidepressant therapies before and subsequently transplant should be aware of united nations-identified risk that will not be recognized by SRTR, and should consider extra monitoring and focused post-transplant care of these recipients.
Our study has limitations. Observational designs tin can make up one's mind associations but cannot evidence causation. The available information do not include detailed clinical information that may explain indications for or contraindications to antidepressant medications or describe mental wellness or adherence behaviors. Chiefly, antidepressant medications may be used for other conditions including feet, obsessive compulsive disorders and neuropathic hurting, or given off-label to treat eating disorders, Tourette syndrome and fibromyalgia. Antidepressant medication utilise is also afflicted by patient willingness to seek care and study symptoms,(26, 28, 29) and prescription records exercise not offering severity information that can exist obtained through surveys and interviews.(49) Our study sample was limited to patients who passed a transplant evaluation and were accounted suitable to undergo transplant, and the severity and outcome implications of depression likely differ in the broader population of patients with end-stage renal illness or waitlisted candidates who never undergo transplant. Futurity projects linking the transplant registry and pharmacy fill records with electronic medical records or surveys may be useful in defining relationships of antidepressant utilize, low symptoms, and outcomes amongst transplant candidates and recipients. Antidepressant employ in the current study was divers in the years before and after transplant, and in the yr earlier listing; boosted studies should examine the bear upon of antidepressant fills over other fourth dimension windows.
In conclusion, based on integration of pharmacy fill records with transplant registry data for a national U.S. sample, we plant that use of antidepressant medications before and later on kidney transplant is more common among women, recipients of white race and those with functional limitations, and has important prognostic implications for patient and allograft survival. Importantly, while pre-listing antidepressant use was also associated with increased mortality compared to no use, transplantation conferred a survival benefit regardless of pre-listing antidepressant employ status. Although the study design and available information are inherently affected by patient-provider communication, these data offer an boosted perspective on treated mental wellness conditions among transplant recipients that complements data obtained through surveys and interviews. Further piece of work including granular measures of patient beliefs, adherence to transplant-related care regimens, and possible bio-behavioral pathways is needed to define the mechanisms of these associations. For now, these data suggest that transplant candidates and recipients who crave antidepressant therapy warrant careful evaluation and management, maybe by a multidisciplinary team including sustained social worker, psychologist and/or psychiatrist support, likewise as focused monitoring of clinical status afterward transplantation.
Supplementary Material
Supp TableS1–four
ACKNOWLEDGEMENTS
This piece of work was conducted under the auspices of the Minneapolis Medical Enquiry Foundation (MMRF), contractor for the Scientific Registry of Transplant Recipients (SRTR), as a deliverable nether contract no. HHSH250201000018C (U.South. Department of Wellness and Human being Services, Health Resources and Services Assistants, Healthcare Systems Agency, Sectionalization of Transplantation). Equally a U.S. Regime-sponsored work, there are no restrictions on its use. The estimation and reporting of these data are the responsibleness of the author(southward) and in no style should be seen as an official policy of or interpretation by the SRTR or the U.South. Authorities. K.50.L., D.A., D.Fifty.South., V.R.D. and D.C.B. receive back up from a grant from the National Institutes of Health (NIH)/National Plant of Diabetes and Digestive and Kidney Diseases (NIDDK) R01- R01DK102981. Northward.N.L. is supported past a KRESCENT New Investigator Award. The opinions, results, and conclusions reported in this article are those of the authors and are independent of the funding sources. The authors thank SRTR colleague Nan Booth, MSW, MPH, ELS, for manuscript editing. An abstract describing this work was accepted for oral presentation at the American Transplant Congress, May 2017, Chicago, IL.
DISCLOSURES
This work was supported past a grant from the National Institutes of Health (NIH)/National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) R01-DK102981. NNL was supported by a KRESCENT New Investigator Award
ABBREVIATIONS:
| aHR | adapted hazard ratio |
| aOR | adjusted odds ratio |
| CES-D | Center for Epidemiologic Studies Depression Scale |
| COPD | chronic obstructive pulmonary disease |
| HADS | Hospital Anxiety and Depression Scale |
| NHANES | National Wellness and Nutrition Exam Survey |
| OPTN | Organ Procurement Transplant Network |
| SAS | Statistical Analysis Software |
| SHS | Symphony Health Solutions |
| SRTR | Scientific Registry of Transplant Recipients |
| SSRI | Selective Serotonin Reuptake Inhibitors. |
Footnotes
Institution at which work was performed: Saint Louis Academy, St. Louis, MO, USA
CONFLICTS OF Interest: The authors written report no conflicts of interest.
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Source: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6334638/
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