Department of Clinical Pharmacy and Translational Science, University of Tennessee Health Science Center College of Pharmacy, Knoxville, TN, USA.
School of Clinical Sciences, University of Louisiana Monroe, Shreveport, LA, USA.
J Pharm Pract. 2023 Dec;36(6):1523-1527. doi: 10.1177/08971900221116009. Epub 2022 Jul 15.
Kratom, an unregulated herbal supplement, has emerged as self-treatment for anxiety/depression. Kratom exhibits inhibition at multiple cytochrome P450 isozymes involved in metabolism of prescription medications, including serotonergic agents. We report a case of possible serotonin syndrome induced by kratom use in combination with prescription psychotropic medications.
A 63-year-old male presented with diaphoresis, flushing, aphasia, confusion, dysarthria, right facial droop, and oral temperature of 39.6C (103.2F), lactate 2.7 mmol/L, and creatine phosphokinase of 1507 IU/L. Initial differential diagnoses included acute ischemic stroke and bacterial meningitis. Despite partial treatment with alteplase and broad-spectrum antibiotics, symptoms persisted, and subsequent physical exam noted hyperreflexia, clonus, tremors, and temperature of 41.1C (106F). Home medications included a chronic regimen for anxiety/depression with bupropion, buspirone, desvenlafaxine, trazodone, and ziprasidone, in addition to kratom. Clinical suspicion for serotonin syndrome led to initiation of cyproheptadine, lorazepam, and cooling blankets. Aphasia, facial droop, and confusion improved after administration of cyproheptadine. Bupropion was restarted during hospitalization; remaining medications restarted at the discretion of the primary care provider.
Risk of serotonin syndrome with multiple serotonergic agents is well-known. Kratom is metabolized by cytochrome P40 isozymes 3A4, 2C9, and 2D6, and exhibits inhibition at those enzymes, in addition to 1A2. Pharmacokinetic interactions of kratom with prescription serotonergic agents metabolized through these isozymes has the potential to increase systemic exposure of serotonin, potentially leading to serotonin syndrome.
Because substances contained in kratom can inhibit metabolism of prescription serotonergic medications, clinicians must be aware of potential development of serotonin syndrome.
Kratom 是一种不受监管的草药补充剂,已成为治疗焦虑/抑郁的自我疗法。Kratom 对参与处方药物代谢的多种细胞色素 P450 同工酶表现出抑制作用,包括 5-羟色胺能药物。我们报告了一例可能由 Kratom 与处方精神药物联合使用引起的 5-羟色胺综合征病例。
一名 63 岁男性出现出汗、潮红、言语不清、意识混乱、构音障碍、右侧面瘫和口腔温度 39.6°C(103.2°F)、乳酸 2.7mmol/L 和肌酸磷酸激酶 1507IU/L。初始鉴别诊断包括急性缺血性中风和细菌性脑膜炎。尽管接受了部分阿替普酶和广谱抗生素治疗,但症状仍持续存在,随后的体格检查发现反射亢进、阵挛、震颤和体温 41.1°C(106°F)。家庭用药包括治疗焦虑/抑郁的慢性方案,包括安非他酮、丁螺环酮、去甲文拉法辛、曲唑酮和齐拉西酮,以及 Kratom。临床怀疑为 5-羟色胺综合征,导致开始使用赛庚啶、劳拉西泮和冷却毯。服用赛庚啶后,言语不清、面瘫和意识混乱得到改善。住院期间重新开始使用安非他酮;其余药物由初级保健提供者酌情重新开始使用。
使用多种 5-羟色胺能药物时,发生 5-羟色胺综合征的风险是众所周知的。Kratom 通过细胞色素 P40 同工酶 3A4、2C9 和 2D6 代谢,并在这些酶以及 1A2 上表现出抑制作用。Kratom 与通过这些同工酶代谢的处方 5-羟色胺能药物的药代动力学相互作用有可能增加 5-羟色胺的全身暴露,从而导致 5-羟色胺综合征。
由于 Kratom 中含有的物质可以抑制处方 5-羟色胺能药物的代谢,因此临床医生必须意识到可能会出现 5-羟色胺综合征。