PharmD Candidate, College of Pharmacy, University of Minnesota, Minneapolis, MN, USA.
Ann Pharmacother. 2012 Dec;46(12):1712-6. doi: 10.1345/aph.1Q748. Epub 2012 Dec 4.
To investigate the nature of the interaction between selective serotonin reuptake inhibitors (SSRIs) and tramadol to mitigate or avoid serotonin syndrome.
PubMed, Ovid MEDLINE, and International Pharmaceutical Abstracts from January 1990 to August 2012 were searched. Key words used were tramadol, antidepressive agents, antidepressants, drug interactions, selective serotonin uptake inhibitors, and serotonin syndrome.
Only English-language studies were included. No randomized controlled trials were identified. Review articles, case reports, and 1 case series that identified the scope of interaction between tramadol and SSRIs were evaluated. Review articles evaluating the role of pharmacogenetics in the use of tramadol, SSRIs, and serotonin syndrome were also reviewed.
Published documentation describing the interaction between tramadol and SSRIs and its relevance to serotonin syndrome is limited to a few case reports and 1 case series. While both tramadol and SSRIs increase the amount of serotonin in the brain, the interaction is much more complicated. Tramadol is metabolized through CYP2D6 enzymes and all SSRIs are inhibitors of these enzymes. Inhibitors of CYP2D6 can increase the concentration of tramadol in the blood and thus increase its effects on serotonin in the brain, contributing to the development of serotonin syndrome. CYP2D6 poor metabolizers are at a greater risk of serotonin syndrome and an inadequate analgesic effect.
Coadministration of tramadol and SSRIs has caused serotonin syndrome. An attempt should be made to identify individuals who are poor metabolizers of CYP2D6 and avoid this combination in those patients. When SSRIs and tramadol must be used in combination, it is critical that patients be aware of the signs and symptoms of serotonin syndrome, should they occur.
研究选择性 5-羟色胺再摄取抑制剂（SSRIs）与曲马多相互作用的性质，以减轻或避免 5-羟色胺综合征。
检索了 1990 年 1 月至 2012 年 8 月的 PubMed、Ovid MEDLINE 和国际药学文摘。使用的关键词有曲马多、抗抑郁药、抗抑郁药、药物相互作用、选择性 5-羟色胺摄取抑制剂和 5-羟色胺综合征。
仅纳入英语文献。未发现随机对照试验。评估了评价曲马多与 SSRIs 相互作用范围的综述文章、病例报告和 1 例病例系列，以及评价药物遗传学在曲马多、SSRIs 和 5-羟色胺综合征应用中的作用的综述文章。
描述曲马多与 SSRIs 相互作用及其与 5-羟色胺综合征相关性的已发表文献仅限于少数病例报告和 1 例病例系列。虽然曲马多和 SSRIs 都能增加大脑中 5-羟色胺的含量，但相互作用要复杂得多。曲马多通过 CYP2D6 酶代谢，所有 SSRIs 都是这些酶的抑制剂。CYP2D6 抑制剂可增加曲马多在血液中的浓度，从而增加其对大脑中 5-羟色胺的作用，导致 5-羟色胺综合征的发生。CYP2D6 弱代谢者发生 5-羟色胺综合征和镇痛作用不足的风险更大。
曲马多与 SSRIs 合用可引起 5-羟色胺综合征。应努力识别 CYP2D6 弱代谢者，并避免在这些患者中使用这种组合。当必须联合使用 SSRIs 和曲马多时，关键是让患者了解 5-羟色胺综合征的体征和症状，如果发生，应立即告知医生。
