The Association of Serotonin Toxicity with Combination Linezolid–Serotonergic Agent Therapy: A Systematic Review and Meta-Analysis
Linezolid (LZD) has a longstanding reported association with the onset of serotonin toxicity (ST), secondary to drug–drug interactions with serotoninergic agents. There have been no conclusive data supporting the incidence or contributing risk factors to date. The study evaluated the incidence of ST...
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| Format: | Article |
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MDPI AG
2023-11-01
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| Series: | Pharmacy |
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| Online Access: | https://www.mdpi.com/2226-4787/11/6/182 |
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| author | Savanna SanFilippo Jacques Turgeon Veronique Michaud Ronald G. Nahass Luigi Brunetti |
| author_facet | Savanna SanFilippo Jacques Turgeon Veronique Michaud Ronald G. Nahass Luigi Brunetti |
| author_sort | Savanna SanFilippo |
| collection | DOAJ |
| description | Linezolid (LZD) has a longstanding reported association with the onset of serotonin toxicity (ST), secondary to drug–drug interactions with serotoninergic agents. There have been no conclusive data supporting the incidence or contributing risk factors to date. The study evaluated the incidence of ST in patients treated with LZD and serotonergic agents concomitantly versus LZD alone. The secondary objectives included a comparison of ST incidence in patients treated with one serotonergic agent + LZD versus two or more serotonergic agents + LZD. The studies used for this meta-analysis were retrieved from PubMed, Scopus, and Google Scholar. All studies including a comparison between LZD alone and LZD + a serotonergic agent published between 1 January 2000 and 1 October 2023 and meeting the quality standards were considered for inclusion. Fourteen studies were identified, with five meeting all inclusion and exclusion criteria with no significant heterogeneity. For the analysis of LZD monotherapy vs. SA combination therapy, four studies with 6025 patients total were analyzed and yielded an odds ratio of 1.78 (CI [1.04, 3.02]; I<sup>2</sup> = 49%; GRADE certainty: low). Four studies and 2501 patients were included in the analysis of one versus more than one SA with an odds ratio of 5.18 (CI [1.05, 25.49]; I<sup>2</sup> = 44.87; GRADE certainty: moderate). The Newcastle–Ottawa score, visual inspection of the funnel plot, and Egger’s statistic were used to evaluate quality and heterogeneity. The Peto method was used to calculate the summary odds ratios. All analyses were performed using Comprehensive Meta-Analysis version 3.0 and R, while GRADE was used to evaluate the quality of the final recommendation. The number of concomitant serotonergic agents may play a role in the development of serotonin toxicity in patients prescribed linezolid. In patients requiring linezolid therapy and serotonergic agents, risk versus benefit analysis should pay attention to the number of interacting drugs. |
| first_indexed | 2024-03-08T20:25:54Z |
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| institution | Directory Open Access Journal |
| issn | 2226-4787 |
| language | English |
| last_indexed | 2024-03-08T20:25:54Z |
| publishDate | 2023-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmacy |
| spelling | doaj.art-4581ff22d08f4a3d889d30b6335361682023-12-22T14:32:27ZengMDPI AGPharmacy2226-47872023-11-0111618210.3390/pharmacy11060182The Association of Serotonin Toxicity with Combination Linezolid–Serotonergic Agent Therapy: A Systematic Review and Meta-AnalysisSavanna SanFilippo0Jacques Turgeon1Veronique Michaud2Ronald G. Nahass3Luigi Brunetti4Robert Wood Johnson University Hospital Somerset, Somerville, NJ 08876, USAGalenus Rx, Orlando, FL 32789, USAGalenus Rx, Orlando, FL 32789, USAIDCare, Hillsborough, NJ 08844, USARobert Wood Johnson University Hospital Somerset, Somerville, NJ 08876, USALinezolid (LZD) has a longstanding reported association with the onset of serotonin toxicity (ST), secondary to drug–drug interactions with serotoninergic agents. There have been no conclusive data supporting the incidence or contributing risk factors to date. The study evaluated the incidence of ST in patients treated with LZD and serotonergic agents concomitantly versus LZD alone. The secondary objectives included a comparison of ST incidence in patients treated with one serotonergic agent + LZD versus two or more serotonergic agents + LZD. The studies used for this meta-analysis were retrieved from PubMed, Scopus, and Google Scholar. All studies including a comparison between LZD alone and LZD + a serotonergic agent published between 1 January 2000 and 1 October 2023 and meeting the quality standards were considered for inclusion. Fourteen studies were identified, with five meeting all inclusion and exclusion criteria with no significant heterogeneity. For the analysis of LZD monotherapy vs. SA combination therapy, four studies with 6025 patients total were analyzed and yielded an odds ratio of 1.78 (CI [1.04, 3.02]; I<sup>2</sup> = 49%; GRADE certainty: low). Four studies and 2501 patients were included in the analysis of one versus more than one SA with an odds ratio of 5.18 (CI [1.05, 25.49]; I<sup>2</sup> = 44.87; GRADE certainty: moderate). The Newcastle–Ottawa score, visual inspection of the funnel plot, and Egger’s statistic were used to evaluate quality and heterogeneity. The Peto method was used to calculate the summary odds ratios. All analyses were performed using Comprehensive Meta-Analysis version 3.0 and R, while GRADE was used to evaluate the quality of the final recommendation. The number of concomitant serotonergic agents may play a role in the development of serotonin toxicity in patients prescribed linezolid. In patients requiring linezolid therapy and serotonergic agents, risk versus benefit analysis should pay attention to the number of interacting drugs.https://www.mdpi.com/2226-4787/11/6/182linezolidserotonin syndromeserotonin toxicityserotonin agonistsdrug interaction |
| spellingShingle | Savanna SanFilippo Jacques Turgeon Veronique Michaud Ronald G. Nahass Luigi Brunetti The Association of Serotonin Toxicity with Combination Linezolid–Serotonergic Agent Therapy: A Systematic Review and Meta-Analysis Pharmacy linezolid serotonin syndrome serotonin toxicity serotonin agonists drug interaction |
| title | The Association of Serotonin Toxicity with Combination Linezolid–Serotonergic Agent Therapy: A Systematic Review and Meta-Analysis |
| title_full | The Association of Serotonin Toxicity with Combination Linezolid–Serotonergic Agent Therapy: A Systematic Review and Meta-Analysis |
| title_fullStr | The Association of Serotonin Toxicity with Combination Linezolid–Serotonergic Agent Therapy: A Systematic Review and Meta-Analysis |
| title_full_unstemmed | The Association of Serotonin Toxicity with Combination Linezolid–Serotonergic Agent Therapy: A Systematic Review and Meta-Analysis |
| title_short | The Association of Serotonin Toxicity with Combination Linezolid–Serotonergic Agent Therapy: A Systematic Review and Meta-Analysis |
| title_sort | association of serotonin toxicity with combination linezolid serotonergic agent therapy a systematic review and meta analysis |
| topic | linezolid serotonin syndrome serotonin toxicity serotonin agonists drug interaction |
| url | https://www.mdpi.com/2226-4787/11/6/182 |
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