Possible Association Between Concomitant Use of SSRIs with NSAIDs and an Increased Risk of Adverse Events Among People with Depressive Disorders: Data Mining of FDA Adverse Event Reporting System
<b>Background</b>: Depression, a major global health issue, is commonly treated with selective serotonin reuptake inhibitors (SSRIs). Given the link between depression and inflammation, nonsteroidal anti-inflammatory drugs (NSAIDs) may have adjunctive benefits. Clinically, SSRIs and NSAI...
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2025-07-01
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| author | Yi Zhang Xiaoyu Liu Jianru Wu Xuening Zhang Fenfang Wei Limin Li Hongqiao Li Xinru Wang Bei Wang Wenyu Wu Xiang Hong |
| author_facet | Yi Zhang Xiaoyu Liu Jianru Wu Xuening Zhang Fenfang Wei Limin Li Hongqiao Li Xinru Wang Bei Wang Wenyu Wu Xiang Hong |
| author_sort | Yi Zhang |
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| description | <b>Background</b>: Depression, a major global health issue, is commonly treated with selective serotonin reuptake inhibitors (SSRIs). Given the link between depression and inflammation, nonsteroidal anti-inflammatory drugs (NSAIDs) may have adjunctive benefits. Clinically, SSRIs and NSAIDs are often co-prescribed for comorbid pain or inflammatory conditions. However, both drug classes pose risks of adverse effects, and their interaction may lead to clinically significant drug–drug interactions. <b>Objectives</b>: This study analyzed FDA Adverse Event Reporting System (FAERS) data (2004–2024) to assess gastrointestinal bleeding, thrombocytopenia, and acute kidney injury (AKI) potential risks linked to SSRIs (citalopram, escitalopram, fluoxetine, paroxetine, fluvoxamine, and sertraline) and NSAIDs (propionic/acetic/enolic acid derivatives, COX-2 inhibitors) in depression patients, alone and combined. <b>Methods</b>: Disproportionality analysis (crude reporting odds ratios, cROR) identified possible associations; drug interactions were evaluated using Ω shrinkage, additive, multiplicative, and combination risk ratio (CRR) models. <b>Results</b>: Gastrointestinal bleeding risk was potentially elevated with citalopram (cROR = 2.81), escitalopram (2.27), paroxetine (2.17), fluvoxamine (3.58), sertraline (1.69), and propionic acid NSAIDs (3.17). Thrombocytopenia showed a potential correlation with fluoxetine (2.11) and paroxetine (2.68). AKI risk may be increased with citalopram (1.39), escitalopram (1.36), fluvoxamine (3.24), and COX-2 inhibitors (2.24). DDI signal analysis suggested that citalopram in combination with propionic acid derivatives (additive model = 0.01, multiplicative model = 1.14, and CRR = 3.13) might increase the risk of bleeding. Paroxetine combined with NSAIDs (additive model = 0.014, multiplicative model = 2.65, and CRR = 2.99) could potentially increase the risk of thrombocytopenia. Sertraline combined with NSAIDs (Ω<sub>025</sub> = 0.94, multiplicative model = 2.14) might be associated with an increasing risk of AKI. Citalopram combined with propionic acid derivatives (Ω<sub>025</sub> = 1.08, multiplicative model = 2.17, and CRR = 2.42) could be associated with an increased risk of acute kidney injury. <b>Conclusions</b>: Certain combinations of SSRIs and NSAIDs might further elevate these risks of gastrointestinal bleeding, thrombocytopenia, and acute kidney injury in patients with depression. Given the potential drug–drug interactions, heightened clinical vigilance is advised when prescribing SSRIs and NSAIDs in combination to patients with depression. |
| format | Article |
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| institution | DOAJ |
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| language | English |
| publishDate | 2025-07-01 |
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| spelling | doaj-art-be008928e46247ceb8b945d700b8a1462025-08-20T03:07:55ZengMDPI AGPharmaceuticals1424-82472025-07-01187106210.3390/ph18071062Possible Association Between Concomitant Use of SSRIs with NSAIDs and an Increased Risk of Adverse Events Among People with Depressive Disorders: Data Mining of FDA Adverse Event Reporting SystemYi Zhang0Xiaoyu Liu1Jianru Wu2Xuening Zhang3Fenfang Wei4Limin Li5Hongqiao Li6Xinru Wang7Bei Wang8Wenyu Wu9Xiang Hong10Key Laboratory of Environmental Medicine and Engineering of Ministry of Education, School of Public Health, Southeast University, Nanjing 210009, ChinaShenzhen Institute of Pharmacovigilance and Risk Management, Shenzhen 518024, ChinaShenzhen Institute of Pharmacovigilance and Risk Management, Shenzhen 518024, ChinaJiangsu Health Development Research Center, Nanjing 210029, ChinaShenzhen Institute of Pharmacovigilance and Risk Management, Shenzhen 518024, ChinaShenzhen Institute of Pharmacovigilance and Risk Management, Shenzhen 518024, ChinaKey Laboratory of Environmental Medicine and Engineering of Ministry of Education, School of Public Health, Southeast University, Nanjing 210009, ChinaKey Laboratory of Environmental Medicine and Engineering of Ministry of Education, School of Public Health, Southeast University, Nanjing 210009, ChinaKey Laboratory of Environmental Medicine and Engineering of Ministry of Education, School of Public Health, Southeast University, Nanjing 210009, ChinaShenzhen Institute of Pharmacovigilance and Risk Management, Shenzhen 518024, ChinaKey Laboratory of Environmental Medicine and Engineering of Ministry of Education, School of Public Health, Southeast University, Nanjing 210009, China<b>Background</b>: Depression, a major global health issue, is commonly treated with selective serotonin reuptake inhibitors (SSRIs). Given the link between depression and inflammation, nonsteroidal anti-inflammatory drugs (NSAIDs) may have adjunctive benefits. Clinically, SSRIs and NSAIDs are often co-prescribed for comorbid pain or inflammatory conditions. However, both drug classes pose risks of adverse effects, and their interaction may lead to clinically significant drug–drug interactions. <b>Objectives</b>: This study analyzed FDA Adverse Event Reporting System (FAERS) data (2004–2024) to assess gastrointestinal bleeding, thrombocytopenia, and acute kidney injury (AKI) potential risks linked to SSRIs (citalopram, escitalopram, fluoxetine, paroxetine, fluvoxamine, and sertraline) and NSAIDs (propionic/acetic/enolic acid derivatives, COX-2 inhibitors) in depression patients, alone and combined. <b>Methods</b>: Disproportionality analysis (crude reporting odds ratios, cROR) identified possible associations; drug interactions were evaluated using Ω shrinkage, additive, multiplicative, and combination risk ratio (CRR) models. <b>Results</b>: Gastrointestinal bleeding risk was potentially elevated with citalopram (cROR = 2.81), escitalopram (2.27), paroxetine (2.17), fluvoxamine (3.58), sertraline (1.69), and propionic acid NSAIDs (3.17). Thrombocytopenia showed a potential correlation with fluoxetine (2.11) and paroxetine (2.68). AKI risk may be increased with citalopram (1.39), escitalopram (1.36), fluvoxamine (3.24), and COX-2 inhibitors (2.24). DDI signal analysis suggested that citalopram in combination with propionic acid derivatives (additive model = 0.01, multiplicative model = 1.14, and CRR = 3.13) might increase the risk of bleeding. Paroxetine combined with NSAIDs (additive model = 0.014, multiplicative model = 2.65, and CRR = 2.99) could potentially increase the risk of thrombocytopenia. Sertraline combined with NSAIDs (Ω<sub>025</sub> = 0.94, multiplicative model = 2.14) might be associated with an increasing risk of AKI. Citalopram combined with propionic acid derivatives (Ω<sub>025</sub> = 1.08, multiplicative model = 2.17, and CRR = 2.42) could be associated with an increased risk of acute kidney injury. <b>Conclusions</b>: Certain combinations of SSRIs and NSAIDs might further elevate these risks of gastrointestinal bleeding, thrombocytopenia, and acute kidney injury in patients with depression. Given the potential drug–drug interactions, heightened clinical vigilance is advised when prescribing SSRIs and NSAIDs in combination to patients with depression.https://www.mdpi.com/1424-8247/18/7/1062drug–drug interactionsadverse eventAdverse Event Reporting SystemFAERS databasedata mining |
| spellingShingle | Yi Zhang Xiaoyu Liu Jianru Wu Xuening Zhang Fenfang Wei Limin Li Hongqiao Li Xinru Wang Bei Wang Wenyu Wu Xiang Hong Possible Association Between Concomitant Use of SSRIs with NSAIDs and an Increased Risk of Adverse Events Among People with Depressive Disorders: Data Mining of FDA Adverse Event Reporting System Pharmaceuticals drug–drug interactions adverse event Adverse Event Reporting System FAERS database data mining |
| title | Possible Association Between Concomitant Use of SSRIs with NSAIDs and an Increased Risk of Adverse Events Among People with Depressive Disorders: Data Mining of FDA Adverse Event Reporting System |
| title_full | Possible Association Between Concomitant Use of SSRIs with NSAIDs and an Increased Risk of Adverse Events Among People with Depressive Disorders: Data Mining of FDA Adverse Event Reporting System |
| title_fullStr | Possible Association Between Concomitant Use of SSRIs with NSAIDs and an Increased Risk of Adverse Events Among People with Depressive Disorders: Data Mining of FDA Adverse Event Reporting System |
| title_full_unstemmed | Possible Association Between Concomitant Use of SSRIs with NSAIDs and an Increased Risk of Adverse Events Among People with Depressive Disorders: Data Mining of FDA Adverse Event Reporting System |
| title_short | Possible Association Between Concomitant Use of SSRIs with NSAIDs and an Increased Risk of Adverse Events Among People with Depressive Disorders: Data Mining of FDA Adverse Event Reporting System |
| title_sort | possible association between concomitant use of ssris with nsaids and an increased risk of adverse events among people with depressive disorders data mining of fda adverse event reporting system |
| topic | drug–drug interactions adverse event Adverse Event Reporting System FAERS database data mining |
| url | https://www.mdpi.com/1424-8247/18/7/1062 |
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