Wellbutrin Gave Me Hives After 2 Weeks Can I Try It Again
PLoS One. 2013; 8(11): e80064.
Delayed Onset Urticaria in Depressive Patients with Bupropion Prescription: A Nationwide Population-Based Written report
Li-Yu Hu
1 Department of Psychiatry, Kaohsiung Veterans General Veterans Hospital, Kaohsiung, Taiwan,
2 Section of Psychiatry, Yuli Veterans Hospital, Yuli, Taiwan,
4 Found of Public Health, National Yang-Ming University, Taipei, Taiwan,
17 National Yang-Ming University, Taipei, Taiwan,
Chia-Jen Liu
3 Division of Hematology and Oncology, Department of Medicine, Taipei Veterans General Infirmary, Taipei, Taiwan,
4 Institute of Public Health, National Yang-Ming Academy, Taipei, Taiwan,
5 Department of Internal Medicine, National Yang-Ming University Infirmary, Yilan, Taiwan,
Ti Lu
i Department of Psychiatry, Kaohsiung Veterans General Veterans Hospital, Kaohsiung, Taiwan,
Find articles by Ti Lu
Tsung-Ming Hu
2 Section of Psychiatry, Yuli Veterans Hospital, Yuli, Taiwan,
Chia-Fen Tsai
6 Section of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan,
17 National Yang-Ming Academy, Taipei, Taiwan,
Yu-Wen Hu
4 Institute of Public Health, National Yang-Ming University, Taipei, Taiwan,
7 Cancer Middle, Taipei Veterans Full general Hospital, Taipei, Taiwan,
Cheng-Che Shen
8 Department of Psychiatry, Chiayi Co-operative, Taichung Veterans General Hospital, Chiayi, Taiwan,
17 National Yang-Ming University, Taipei, Taiwan,
Yu-Sheng Chang
4 Plant of Public Health, National Yang-Ming University, Taipei, Taiwan,
9 Division of Allergy, Immunology, and Rheumatology, Department of Internal Medicine, Shuang Ho Hospital, New Taipei City, Taiwan,
10 Taipei Medical Academy, New Taipei Urban center, Taiwan,
Mu-Hong Chen
six Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan,
Chung-Jen Teng
11 Division of Oncology and Hematology, Section of Medicine, Far Eastern Memorial Hospital, New Taipei Metropolis, Taiwan,
17 National Yang-Ming University, Taipei, Taiwan,
Huey-Ling Chiang
12 Department of Psychiatry, Far Eastern Memorial Infirmary, New Taipei Urban center, Taiwan,
13 Department of Psychiatry, National Taiwan Academy Hospital, Taipei, Taiwan,
Chiu-Mei Yeh
14 Department of Family unit Medicine, Taipei Veterans General Hospital, Taipei, Taiwan,
Vincent Yi-Fong Su
fifteen Department of Chest Medicine, Taipei Veterans General Infirmary, Taipei, Taiwan,
Wei-Shu Wang
5 Section of Internal Medicine, National Yang-Ming University Hospital, Yilan, Taiwan,
17 National Yang-Ming University, Taipei, Taiwan,
Pan-Ming Chen
16 Department of Psychiatry, Su-Ao and Yuanshan Co-operative, Taipei Veterans General Hospital, Taipei, Taiwan,
Tzeng-Ji Chen
14 Department of Family Medicine, Taipei Veterans General Hospital, Taipei, Taiwan,
17 National Yang-Ming University, Taipei, Taiwan,
Tung-Ping Su
half-dozen Department of Psychiatry, Taipei Veterans Full general Hospital, Taipei, Taiwan,
17 National Yang-Ming University, Taipei, Taiwan,
James M Wright, Editor
Received 2013 May xiv; Accepted 2013 October 8.
- Supplementary Materials
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Table S1: Scaled Schoenfeld residuals test of proportional hazards.
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GUID: AEA6FDAE-5A30-4C7E-9877-D7A9A8EAC807
Table S2: Incidence of dermatologist-diagnosed urticaria occurrence in depressive patients within beginning 4 weeks.
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GUID: 9ABFA037-A58A-4B58-AB94-53B3AA7A69E0
Table S3: Comparisons of early and delayed onset dermatologist-diagnosed urticaria occurrence.
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GUID: D4BB3B15-F833-4CD1-B3C0-78D3884380A9
Abstract
Background
Bupropion, which is widely used in patients with depressive disorder, may cause allergic reactions. However, the real prevalence of these side effects may be disregarded and underreported due to the delayed onset phenomenon.
Objective
This study aimed to approximate the real incidence of bupropion-induced urticaria and clarify the delayed onset phenomenon.
Methods
We conducted a nationwide cohort study between 2000 and 2009 using Taiwan'south National Wellness Insurance Dataset. Among 65,988 patients with depressive disorders, nosotros identified new users of bupropion with depressive disorders (bupropion cohort, northward = 2,839) and matched them at a ratio of 1:4 regarding age and sexual practice (not-bupropion matched cohort, n = 11,356). The take chances of urticaria was compared betwixt the ii cohorts.
Results
The risk of urticaria occurrence was higher in bupropion users than in matched controls within 4 weeks of starting the medication (risk ratio 1.81; 95% confidence interval 1.28–2.54; p = 0.001). The occurrence of urticaria in the bupropion cohort were more frequent on Days 15–28 than Day 1–xiv (p = 0.002). Cox proportional hazards model showed that a history of urticaria was an independent risk gene for developing bupropion-induced urticaria.
Conclusions
Of the antidepressants, bupropion may pose a higher chance of drug-induced urticaria, and this condition might be ignored due to the delayed onset miracle. Depressive patients with a history of urticaria are at higher risk of the adverse drug reaction. This report emphasizes the need for increased clinical awareness of this adverse outcome to bupropion use.
Introduction
Bupropion hydrochloride is a pop psychotropic drug that inhibits norepinephrine and dopamine reuptake with minimal effect on serotonin. It is prescribed to millions of patients worldwide for the treatment of major depressive disorders and bipolar depression. In 1997, bupropion was approved by the U.S. Food and Drug Administration (FDA) for utilize every bit a smoking cessation assistance[i,2].
The U.S. prescribing information for bupropion discloses serious allergic reactions as potential side effects, including urticaria, angioedema, erythema multiforme, Stevens-Johnson syndrome, and even anaphylactic shock. However, these allergic reactions take been rarely reported with bupropion[3]. Two large-scale studies were designed to examine the safety of bupropion as a treatment for smoking cessation in England and French republic, respectively[iv,5]; however, cess of allergic reactions was not emphasized in these studies. In addition, adverse effects of bupropion in depressive patients, which had been highly associated with urticaria[6], is rarely mentioned in the literature.
To engagement, but case reports have described bupropion-induced allergic reactions, and it is important to note that clinical features of delayed onset urticaria seems to be nowadays in nearly of these patients[7-x]. Some studies have postulated that delayed onset urticaria may be disregarded and underreported[9,11] because patients who take bupropion may receive handling for bupropion-induced delayed onset urticaria by other physicians or hospitals[ix,11].
To address these inadequacies in the literature and to assess the design of bupropion-induced urticaria, nosotros designed a nationwide population-based study to investigate the bodily incidence and timing of new onset urticaria in patients with low who receive bupropion prescriptions.
Patients and Methods
Data Sources
The Taiwan National Health Insurance (NHI) program offers a comprehensive, unified, and universal health insurance program to all citizens. The NHI plan covers more than than 96% of the country'south population and has contracted with 99% of all hospitals and clinics in Taiwan[12]. The NHI dataset covers comprehensive medical care, including complete data on outpatient visits, hospitalizations, diagnostic codes, examinations, and prescriptions. Multiple NHI databases (east.yard., NHI enrolment files, claims data, and prescription drug registry) are managed and publicly released by the National Health Research Institute, Taiwan. The Agency of National Health Insurance and the National Health Research Institute regulations guarantee patient confidentiality, and data that may have contained identifiable information were encrypted. Our study received full review by our local institutional review board (Veterans General Infirmary Institutional Review Board NO. : 2013-01-035BC) and our institutional review board has waived the demand for written informed consent from the participants.
Patient Population
We conducted a retrospective accomplice study from January one, 2000 to Dec 31, 2009. The presence of depressive disorders was divers as any divers in the International Classification of Diseases, 9th revision, and the clinical modification (ICD-9-CM) codes 296.2X-296.3X, 300.4, and 311.X[13,14]. We also collected information on all types of antidepressants which were available in Taiwan. Antidepressants were classified according to the World Wellness Organization (WHO) Anatomical Therapeutic Chemical (ATC) nomenclature.
For the study cohort, we identified 65,988 patients with depressive disorders who had received a first prescription for antidepressants (ATC code N06A) available in Taiwan betwixt Jan 1, 2000 and December 31, 2009. Patients with a new prescription of bupropion were assigned to the bupropion cohort. Patients who had received bupropion before 2000 or under 20 years of historic period were excluded. We used the date on which the bupropion handling was first prescribed as the alphabetize engagement. Within the same observational period, for each of the 2,839 depressive patients taking bupropion, 4 insured people in the comparison cohort with other antidepressants employ matched for age, sex, comorbidities, and alphabetize date were selected. The aforementioned exclusion criteria were applied to the matched comparing cohort. The other antidepressants used in the comparison cohort included fluoxetine, paroxetine, sertraline, citalopram, escitalopram, fluvoxamine maleate, venlafaxine, duloxetine, milnacipran, mirtazapine, trazodone, moclobemide, imipramine, amitriptyline, doxepin, maprotiline, clomipramine, dothiepin. The comparing group included 11,356 patients. In our study, the follow-up began on the index date and will finish on 4 weeks afterward.
Nosotros defined patients with an urticaria occurrence as those under ICD-nine-CM codes 708.x within four weeks of receiving a bupropion prescription. Patients with contempo urticaria inside i calendar month before receiving the new prescription of bupropion were excluded from the study. A history of urticaria was divers as urticaria occurring at least one calendar month before the alphabetize date. The medical history could be traced because the NHIRD in Taiwan was established in 1996.
Patient comorbidities at baseline were identified. Comorbidities included autoimmune diseases (ICD-9-CM code 279.10), liver diseases (ICD9-CM codes 570-573), diabetes mellitus (ICD-nine-CM codes 250), chronic kidney diseases (ICD-9-CM codes 580-593), and HIV/AIDS (ICD-9-CM code 042).
Each study patient was tracked until one of the post-obit atmospheric condition was met: a diagnosis of urticaria (ICD-nine-CM codes 708.x), follow-up was censored at the fourth dimension of loss to follow-up, death, the patient withdrew from the NHI, or the follow-up menses elapsed (iv weeks after index date).
In addition, to clarify whether other antidepressants could take the aforementioned delayed onset phenomenon on urticaria occurrence, we compared urticaria occurrence in patients receiving a new bupropion prescription with patients receiving new prescriptions for all other antidepressants available in Taiwan within the next four weeks as a farther analysis.
Statistical Analyses
Urticaria occurrence was considered as the primary outcome variable in this written report and was calculated for two different time periods afterwards the depressive patients receiving the new antidepressants prescription, i.eastward., Day 1–14 and Day 15–28. We first compared the distribution of demographic characteristics betwixt the bupropion accomplice and the comparison grouping using the Mann-Whitney U test for median age and using χ2 test for sex and baseline comorbidities. The cumulative incidence of urticaria for the two cohorts were calculated past the Kaplan-Meier method, with the log-rank test beingness used to examine differences between cohorts. Cox proportional hazards model was used to identify risk factors for urticaria occurrence in depressive patients with bupropion prescription inside 4 weeks. We implemented in both the univariate and multivariable fashion to identify risk factors for the urticaria occurrence after bupropion utilize. Variables included in the model were sex, age, comorbidities, and history of urticaria. The qualifying criterion for inclusion in the multivariate analysis was a result in the univariate-analysis with a P value of less than 0.1. In constructing Cox models, the follow-up began on the index date. The study patients who withdrew (including those who died) from the NHI plan were censored. If the patient did not leave the NHI plan and encountered no urticaria occurrence, the date of censoring was the engagement of the end of follow-upward. We validated the Cox regression model by checking whether the assumption of proportionality held. The results of Scaled Schoenfeld Reiduals test shown the proportionality of hazards assumption was met in this assay (Table S1). Finally, in social club to brand the diagnosis of urticaria more specific, the subgroup of urticaria patients diagnosed by dermatologic specialists were determined.
The Perl programming linguistic communication (version five.12.2) extracted and computed data. Microsoft SQL Server 2005 (Microsoft Corp., Redmond, WA, The states) was used for data linkage, processing, and control sampling. IBM SPSS (version 19.0 for Windows; IBM Corp., New York, NY, USA) and SAS statistical software (version 9.2; SAS Plant Inc., Cary, NC, United states) were used for all statistical analyses. Results of comparisons with a p value less than .05 were considered statistically significant.
Results
Written report Population Characteristics
Characteristics of patients in the bupropion and comparison cohort are shown in Table one. Of the written report population, 2,839 of 65,988 (four.3%) patients with depressive disorders had received bupropion and 11,356 of 65,988 (17.2%) patients were selected to match the bupropion cohorts based on age and sex from Jan 1, 2000 to December 31, 2009. The median age of the subjects was 41 years (interquartile range: 31–52 years). The majority of patients in both cohorts were female (sixty.16%). Liver diseases and diabetes mellitus, found in 33.3% and 20.three% of patients, respectively, were the two most common observed comorbidities. A by history of urticaria was recorded in 31.32% of patients. There were no baseline statistical differences in comorbidities and history of urticaria between the groups.
Table i
Characteristics of depressive patients with a bupropion prescription and the matched cohort.
| Characteristics | Bupropion cohort (n = 2,839) | Matched cohort (n = xi,356) | p value | |
|---|---|---|---|---|
| Full no. (%) | Total no. (%) | |||
| Median historic period (interquartile range) | 41(31–54) | 41(31–54) | ||
| 20–39 | 1,276(44.95) | 5,104(44.95) | 1.000 | |
| twoscore–59 | i,050(36.98) | 4,200(36.98) | ||
| ≥ 60 | 513(18.07) | 2,052(eighteen.07) | ||
| Sex | ||||
| Male | ane,131(39.84) | 4,524(39.84) | 1.000 | |
| Female | 1,708(60.xvi) | half-dozen,832(sixty.xvi) | ||
| Comorbidities | ||||
| Autoimmune diseases | 313 (11.03) | 1145 (x.08) | 0.139 | |
| Liver diseases | 958(33.74) | iii,724(32.79) | 0.335 | |
| Diabetes mellitus | 591(xx.82) | 2,242(19.74) | 0.200 | |
| Chronic kidney diseases | 323(11.38) | 1,368(12.05) | 0.325 | |
| AIDS | iv(0.14) | 31(0.27) | 0.204 | |
| History of urticaria | 899(31.67) | 3,517(thirty.97) | 0.474 |
Incidence of Urticaria
Figure 1 shows the cumulative incidences of urticaria occurrence across all participants. The urticaria risk inside iv weeks was significantly higher for patients in the bupropion cohort (cumulative incidence, 16.56‰) than for patients in the comparison accomplice (9.xvi‰) (gamble ratio, one.81; 95% CI one.28–2.54, p = 0.001) (Table two). We too stratified patients by age and gender and institute that bupropion use was associated with college urticaria adventure in patients under 40 years of age (risk ratio, 2.25; 95% CI 1.41–iii.60, p < 0.001), simply not in patients over twoscore years of age. The use of bupropion was associated with a college gamble of urticaria occurrence in both males and females.
The cumulative incidences of urticaria in depressive patients with and without bupropion prescription.
Follow-up(days) =0 indicates the initiation of antidepressants use.
Table two
Incidence of urticaria occurrence in depressive patients inside the kickoff 4 weeks of taking the antidepressants.
| Bupropion cohort | Matched accomplice | Risk ratio | p value | |
|---|---|---|---|---|
| n (‰) | n (‰) | (95% CI) | ||
| Full | 47(16.56) | 104(9.16) | 1.81 (one.28–2.54) | 0.001 |
| Age | ||||
| 20–39 | 27(21.16) | 48(9.40) | 2.25(ane.41–three.60) | < 0.001 |
| xl–59 | 15(14.29) | 39(9.29) | 1.54(0.85–2.78) | 0.151 |
| ≥ 60 | 5(9.75) | 17(8.28) | ane.18(0.44–iii.17) | 0.748 |
| Sexual activity | ||||
| Male | 16(xiv.fifteen) | 33(7.29) | i.94 (one.07–iii.51) | 0.026 |
| Female person | 31(18.15) | 71(ten.39) | 1.75 (1.15–2.65) | 0.008 |
Early on and Delayed Onset Urticaria
Equally shown in Tabular array three, we compared the cumulative incidences of urticaria occurrence in the Day one–14 and the Day 15–28 between bupropion and matched cohorts. The results indicated that delayed onset urticaria occurred more frequently for patients in the bupropion cohort (cumulative incidence, 11.98‰) than for patients in the non-bupropion cohort (5.11‰) (risk ratio, 2.34; 95% CI 1.54–3.57, p < 0.001).
Table 3
Comparisons of early and delayed onset urticaria occurrence.
| Bupropion cohort | Matched cohort | Run a risk ratio | p value | |
|---|---|---|---|---|
| n (‰) | n (‰) | (95% CI) | ||
| Total | 47(16.56) | 104(9.16) | 1.81 (i.28–2.54) | 0.001 |
| Early onset (Day 1–14) | 13(four.58) | 46(four.05) | ane.thirteen(0.61-2.09) | 0.696 |
| Delayed onset (Day fifteen–28) | 34(eleven.98) | 58(v.11) | two.34(1.54-3.57) | <0.001 |
Risks Factors for Urticaria
Nosotros next performed univariate and multivariable analyses to predict urticaria evolution in the bupropion accomplice (Table 4). We found that a history of urticaria (HR iii.03, 95% CI 1.7–5.4, p < 0.001) was the only contained adventure factor for urticaria occurrence following bupropion utilise.
Tabular array 4
Analyses of risk factors for urticaria in depressive patients after bupropion employ.
| Variables | Univariate analysis | Multivariable assay | ||||
|---|---|---|---|---|---|---|
| 60 minutes | 95% CI | p value | HR | 95% CI | p value | |
| Historic period | 0.98 | 0.96–1.00 | 0.101 | 0.99 | 0.97–1.01 | 0.367 |
| Male sex | 0.78 | 0.43–1.43 | 0.424 | |||
| Comorbidities | ||||||
| Autoimmune diseases | 0.75 | 0.27–2.09 | 0.580 | |||
| Liver diseases | 0.74 | 0.39–1.twoscore | 0.358 | |||
| Diabetes mellitus | 0.35 | 0.13–0.98 | 0.046 | 0.38 | 0.xiii–1.ten | 0.075 |
| Chronic kidney disease | ane.59 | 0.74–3.twoscore | 0.232 | |||
| AIDS | 0.05 | 0.00–2.12x10thirteen | 0.861 | |||
| History of urticaria | 2.94 | 1.65–5.24 | < 0.001 | 3.02 | i.69–5.39 | <0.001 |
Delayed onset Urticaria in depressive patients with all types of newly antidepressants prescription
To clarify whether other antidepressants could have the same delayed onset phenomenon on urticaria occurrence, nosotros compared the cumulative incidences of urticaria in depressive patients with patients receiving all other types of new antidepressant prescriptions in Taiwan (Tabular array 5). Bupropion-associated urticaria occurred more ofttimes on 24-hour interval fifteen–28 (11.98‰) than on 24-hour interval one–14 (4.58‰) (risk ratio, 2.62, 95% CI 1.38–4.95, p = 0.002). Amid all antidepressants, the delayed-onset phenomenon was simply observed in bupropion users.
Table 5
The risk of urticaria occurrence among all antidepressant classes.
| Antidepressant classes | Total new prescriptions | Urticaria occurrence on Day one-14 n (‰) | Urticaria occurrence on Day fifteen-28 n (‰) | Risk ratio (95% CI) | p-value |
|---|---|---|---|---|---|
| Norepinephrine-Dopamine Reuptake Inhibitors | |||||
| Bupropion | 2,839 | thirteen(four.58) | 34(11.98) | two.62 (1.38–four.95) | 0.002 |
| Serotonin-Norepinephrine Reuptake Inhibitors | |||||
| Venlafaxine | 7,240 | 24(3.31) | 35(4.83) | i.46 (0.87–2.45) | 0.151 |
| Duloxetine | 1,752 | 7(four.00) | 5(2.85) | 0.71 (0.23–ii.25) | 0.563 |
| Milnacipran | 658 | 5(7.60) | 2(iii.04) | 0.4 (0.08–2.05) | 0.452 |
| Selective Serotonin Reuptake Inhibitors | |||||
| Fluoxetine | xiii,207 | 54(iv.09) | 61(four.62) | one.13 (0.78–1.63) | 0.513 |
| Paroxetine | viii,454 | 34(4.02) | 32(3.79) | 0.94 (0.58–1.52) | 0.805 |
| Sertraline | x,747 | 39(3.63) | 33(3.07) | 0.85 (0.53–one.34) | 0.479 |
| Citalopram | v,973 | 23(iii.85) | 21(iii.52) | 0.91 (0.51–ane.65) | 0.763 |
| Escitalopram | iii,817 | 13(three.41) | 13(3.41) | 1 (0.46–ii.fifteen) | 1.000 |
| Fluvoxamine Maleate | three,057 | x(iii.27) | 12(3.93) | i.2 (0.52–two.77) | 0.669 |
| Tricyclics | |||||
| Imipramine | 8,296 | 46(5.54) | 34(four.10) | 0.74 (0.48–1.15) | 0.179 |
| Amitriptyline | iii,426 | 20(5.84) | 11(3.21) | 0.105 | |
| Doxepin | 4,018 | 33(viii.21) | fourteen(3.48) | 0.42 (0.23–0.79) | 0.005 |
| Maprotiline | 919 | 6(half dozen.53) | 1(1.09) | 0.17 (0.02–1.38) | 0.124 |
| Clomipramine | 667 | four(vi.00) | 3(4.50) | 0.75 (0.17–3.34) | 1.000 |
| Dothiepin | 286 | 1(three.50) | two(6.99) | 2 (0.xviii–21.93) | ane.000 |
| Monoamine Oxidase Inhibitors | |||||
| Moclobemide | 3653 | 11(3.01) | thirteen(3.56) | one.18 (0.53–2.63) | 0.683 |
| Others | |||||
| Mirtazapine | 5164 | 15(2.ninety) | 14(ii.71) | 0.93 (0.45–1.93) | 0.853 |
| Trazodone | 14961 | 66(4.41) | 44(2.94) | 0.67 (0.46–0.98) | 0.036 |
Urticaria patients among both cohorts diagnosed by dermatologic specialists
In this subgroup of dermatologist-diagnosed urtiacria amid both cohorts, the higher risk for overall urticaria occurrence was like to the results of the urtiacria patients diagnosed by general practitioners in the bupropion cohort. The bupropion use was yet associated with higher urticaria adventure in patients under forty years of age (take chances ratio, 2.95; 95% CI 1.48–5.86, p = 0.001), just not in patients over twoscore years of age. The higher run a risk of urticaria occurrence in the bupropion accomplice was meaning in males but not in females (take chances ratio, 1.47; 95% CI 0.74–2.92, p = 0.273). In addition, the delayed onset trend of urticaria occurrence was still institute in this subanalysis (take a chance ratio, 2.73; 95% CI 1.42–5.25, p = 0.002). Detailed results are shown in the Tables S2-S3.
Discussion
To the best of our knowledge, the present report is possibly the largest study to analyze urticaria risk in patients with low after starting a bupropion prescription. At that place are several important findings from the nationwide study. First, the unexpected high chance for urticaria occurrence was observed in patients with low who received bupropion, especially in patients under 40 years of age. Second, the adventure of urticaria occurrence in bupropion accomplice were significantly higher in 24-hour interval 15–28 than Twenty-four hours ane–14 and the delayed onset trend was not observed in other antidepressants users in our study. Finally, a history of urticaria may be an of import predictor of urticaria development subsequently taking bupropion. The findings may arouse public interest regarding safety issues in bupropion use.
In order to examine the safety of bupropion utilise, two large-scale studies were previously conducted to quantify the incidence of events reported for patients who were prescribed bupropion and to identify whatsoever previously unrecognized adverse drug reactions in England and French republic[4,5]. In the report conducted in England, data were derived from questionnaires sent to general practitioners at to the lowest degree half dozen months following the first prescription. Nonetheless, the study accomplished a response charge per unit of only 48.i% in the patients prescribed bupropion, and therefore a recall and option bias could not be avoided. In the French report, the safety profile of bupropion use was monitored through a spontaneous report system; thus, the results may be underestimated. The design of those previous studies may explicate why the incidence of bupropion-induced urticaria was much lower than that establish in our written report. Although those studies provide insight into the clan between bupropion administered for smoking abeyance and urticaria, the clan betwixt bupropion administered for low and unitcaria is rarely mentioned in the literature, and importantly low has been shown to be strongly associated with urticaria[6]. In addition, our study relied on a claim-based dataset, and therefore the data related to the medical charge, such as antidepressant utilise, were precise. A diagnosis of urticaria would non be omitted even if the patients had received treatment at different hospitals or times.
Several smaller reports accept shown that nearly all of the antidepressants seemed to be associated with an onset of urticaria, including fluoxetine[15], paroxetine[16], sertraline[17], escitalopram[17], venlafaxine[18], bupropion[5,7,9,x,19-25], mirtazapine[18], and tricyclic antidepressants[26]. Nonetheless, very few attempts take been fabricated to compare the occurrence of urticaria among the various antidepressants. In our study, the results showed that bupropion utilize was associated with the highest risk of urticaria development and the delayed onset miracle of urticaria occurrence was only shown in the bupropion users compared with all other antidepressant prescriptions in Taiwan assessed.
In improver to bupropion-induced urticaria[21-23], many smaller studies take described a human relationship between bupropion use and allergic reactions, including angioedema[20], erythema multiform[24], Stevens-Johnson syndrome[27], and serum sickness-like reactions[7-eleven,25]. Moreover, near of the studies noticed delayed onset characteristics of these allergic reactions. Although some researchers had presumed that the bupropion-induced urticaria may be underestimated[ix,11], unanswered reasons still remain. According to our results, nosotros hypothesized that the reason of underestimation may be related to the delayed onset miracle of bupropion-induced urticaria. In improver, bupropion-induced urticaria seldom develops alone and is sometimes accompanied with other more serious allergic reactions, including angioedema[19,twenty], arthralgia[viii], serum sickness-similar reaction[7,9-eleven], or symptoms of anaphylaxis, which may indicate a medical emergency. Therefore, if medical personnel practise not recognize the agin drug reaction, then patients could be put at risk for more than astringent drug hazards.
The mechanisms of urticaria are thought to be associated with histamine and other mediators being released from mast cells and basophils. The college occurrence of bupropion-induced urticaria in younger patients could be explained by immunosenescence, which is an age-related reject in immune functions. It has been reported that mast prison cell development declines through the aging procedure[28], and the number of dermal mast cells decreases with historic period in human subjects[29]. However, the mechanism of bupropion-induced urticaria is currently unknown. We hypothesize that the adverse drug reaction may be linked to the structure of bupropion, which is chemically similar to amfepramone. Amfepramone is considered a selective norepinephrine releasing agent, and norepinephrine may play an important role in adrenergic urticaria, which is considered to be a form of neurogenic reaction that is mainly triggered by stress. Moreover, in recent years, bupropion has been suggested to accept effects every bit an anti-inflammatory agent by downward-regulating tumor necrosis factor synthesis, which may slow the course of some inflammatory processes[30,31]. Therefore, we hypothesized that the anti-inflammation issue may delay the allergic reaction and lead to delayed onset urticaria.
While urticaria may be confused with a variety of other dermatologic diseases that are similar in advent and are too pruritic, it is possible that other urticaria-like pare reactions may have been misclassified under the code based on claims information. In order to make the diagnosis more specific, subgroup of the urtiacria diagnosed by dermatologic specialists in our written report grouping were further analyzed and the higher chance for overall urticaria occurrence and delayed onset tendency were like to the results of the urtiacria patients diagnosed by general practitioners in the bupropion cohort.
Several limitations inherent in using claims databases as well need to be taken into consideration. Beginning, because patients' identifications were blocked for protection of privacy, we accept no style to assess for bodily intake of prescribed antidepressants. However, such a limitation usually leads toward an under-interpretation of adventure. Also, although no show has shown that the departure of drug compliance between bupropion and other antidepressants, it is reasonable to assume that the higher take a chance of delayed onset urticaria in the bupropion cohort may exist associated with the influence of drug compliance. Second, drugs which may cause were non adjusted for. Although urticaria is actually ofttimes acquired by the many drugs including antibiotics and anticonvulsants use in our clinical experience. All the same, these drugs were non selected for adjustment in this study because the antibiotics and anticonvulsants were less common co-medications used by our written report subjects (patients with depressive disorders). Also, the frequency of antibiotics and anticonvulsants co-prescriptions with antidepressants is relatively low during a short follow-up menstruum (4 weeks) in our study. Third, a number of other potential confounding factors that might affect urticaria hazard were not available in the reimbursement data used in this report, such as psychosocial stresses, foods, family unit history of urticaria, recent travel history, exposure to environmental stimulants and smoking[32]. {Stockli, 2007 #51}Among these non-observable confounders, for the reason that the employ of bupropion may be helpful to depressive patients who smoke[33], therefore, smoking may be an of import non-observable confounder in our written report. Finally, farther investigations are needed to explore such associations in different populations and ethnic groups.
In decision, our study has found that patients with depressive disorders who received bupropion were at an unusually higher risk for delayed onset urticaria. Based upon our data, nosotros advise that more attending should be focused on the bupropion-induced urticaria in patients with depressive disorders and urge circumspection over the delayed onset phenomenon, especially in patients under xl years of historic period and with past history of urticaria, in social club to avoid more severe drug allergies as a outcome of prescribing the same drugs. Although more research is needed, this article serves to broaden physicians' noesis base when prescribing bupropion.
Supporting Information
Tabular array S1
Scaled Schoenfeld residuals test of proportional hazards.
(DOC)
Table S2
Incidence of dermatologist-diagnosed urticaria occurrence in depressive patients within first four weeks.
(Md)
Table S3
Comparisons of early and delayed onset dermatologist-diagnosed urticaria occurrence.
(DOC)
Acknowledgments
Nosotros thank Huei-Sing Chang and Cheng-Fang Hong for technical support.
Funding Argument
This study was supported past grants from Taipei Veterans Full general Hospital (V102D-001-1 and V102D-001-2) and Yuli Veterans Infirmary (VHYL-102-08). The funders had no function in study design, information collection and analysis, decision to publish, or preparation of the manuscript.
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Source: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3828225/
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