Desvenlafaxine overdose and the occurrence of serotonin toxicity, seizures and cardiovascular effects

<b>Context:</b> Desvenlafaxine is used to treat major depression. Desvenlafaxine is also the active metabolite of venlafaxine. Venlafaxine overdose can cause serotonin toxicity, seizures and cardiovascular effects, but there is limited information on desvenlafaxine overdose. <b>Objective:</b> We aimed at investigating the clinical effects and complications from desvenlafaxine overdose. <b>Materials and methods:</b> This was a retrospective observational study of desvenlafaxine overdoses over a six-year period. Demographic details, dose and timing of the overdose, together with clinical effects, treatment and complications were extracted from a local hospital network database or the medical records of patients following hospital admission with a desvenlafaxine overdose. <b>Results:</b> There were 182 cases of desvenlafaxine overdose included in the study. From the 182 cases, 75 were desvenlafaxine (± alcohol) only ingestions and 107 included one or more co-ingested drugs. In single-agent desvenlafaxine ingestions, median age was 25 years (range: 13–68 years) with a median ingested dose of 800 mg (range: 250–3500 mg; interquartile range (IQR): 600–1400 mg), and 54/75 (72%) were female. The Glasgow Coma Score (GCS) was 15 in 68/74 (92%) patients, 13–14 in 5/74 (7%), and was seven in one patient following aspiration. Mild hypertension (systolic blood pressure [BP] &gt; 140–180 mmHg) occurred in 23/71 patients (32%), and tachycardia occurred in 29/74 (39%) patients. There were no abnormal QT intervals and no QRS &gt;120 m s. Serotonin toxicity was diagnosed by the treating physician in 7/75 (9%) patients, but only one of these met the Hunter Serotonin Toxicity Criteria. None of the 75 patients who took desvenlafaxine only (± alcohol) had seizures, were admitted to intensive care or died. In comparison, the 107 patients taking desvenlafaxine in overdose with other medications developed more pronounced toxicity. Generalised seizures occurred in 5/107 (5%), but in three of these cases co-ingestants were possible proconvulsants. Fifteen patients had a GCS ≤9 and none had an abnormal QT or QRS. Severe effects appeared to be associated with coingestants. <b>Conclusion:</b> Desvenlafaxine overdose causes minor effects with mild hypertension and tachycardia. The risk of seizures or serotonin toxicity is low.

<b>背景:</b> 去甲文拉法辛（desvenlafaxine）用于治疗重度抑郁症，同时也是文拉法辛（venlafaxine）的活性代谢产物。文拉法辛过量可引发5-羟色胺毒性（serotonin toxicity）、癫痫发作及心血管不良反应，但目前关于去甲文拉法辛过量的相关研究资料仍较为有限。<b>研究目的:</b> 本研究旨在探讨去甲文拉法辛过量服用后的临床效应与并发症情况。<b>材料与方法:</b> 本研究为一项回顾性观察性研究，纳入了6年间收录的去甲文拉法辛过量服用病例。研究人员从当地医院网络数据库或因去甲文拉法辛过量入院患者的病历中，提取了患者人口学特征、服药剂量与服药时间、临床效应、治疗方案及并发症等相关数据。<b>研究结果:</b> 本研究共纳入182例去甲文拉法辛过量服用病例。其中75例为仅服用去甲文拉法辛（±酒精）的单一用药过量病例，剩余107例为同时服用1种及以上其他药物的合并用药过量病例。在单一去甲文拉法辛（±酒精）用药过量组中，患者年龄中位数为25岁（范围：13~68岁），服药剂量中位数为800mg（范围：250~3500mg；四分位间距（interquartile range，IQR）：600~1400mg），其中女性患者54例，占比72%（54/75）。74例患者的格拉斯哥昏迷评分（Glasgow Coma Score，GCS）为15分，5例为13~14分，另有1例因误吸导致GCS为7分。23例患者出现轻度高血压（收缩压[BP]＞140~180mmHg），占该组可获取血压数据患者的32%（23/71）；29例患者出现心动过速，占比39%（29/74）。未观察到QT间期异常及QRS波群宽度＞120ms的情况。经接诊医师诊断，7例患者（9%，7/75）出现5-羟色胺毒性，但仅1例符合亨特5-羟色胺毒性诊断标准。该75例单一用药（±酒精）过量患者均未出现癫痫发作、入住重症监护病房或死亡的情况。相较而言，107例合并其他药物服用去甲文拉法辛过量的患者，其毒性反应更为显著。其中5例患者（5%，5/107）出现全面性癫痫发作，其中3例的合并用药可能具有致惊厥作用。15例患者的GCS≤9分，未出现QT间期异常或QRS波群异常的情况。研究观察到严重不良反应与合并用药存在关联。<b>研究结论:</b> 去甲文拉法辛过量服用仅会引发轻度不良反应，主要表现为轻度高血压与心动过速，癫痫发作或5-羟色胺毒性的发生风险较低。