Department of Neurology, University Hospital of Schleswig-Holstein, Lübeck, Germany.
Institute of Social Medicine and Epidemiology, University of Lübeck, Lübeck, Germany.
Eur J Neurol. 2021 Jul;28(7):2349-2356. doi: 10.1111/ene.14773. Epub 2021 Mar 1.
Many drugs can worsen myasthenia symptoms. The clinician usually relies on cautionary lists compiled according to case reports. We intended to provide a quantitative basis for a risk comparison within the groups of antiepileptic, antidepressant, neuroleptic, and sedative drugs.
We extracted adverse drug reaction (ADR) counts (total and myasthenia related) for drugs from these groups and calculated the reporting odds ratio (ROR) within the drug groups from the World Health Organization pharmacovigilance database. For a given drug, the ROR was increased above 1 if the proportion of myasthenia-related ADRs for this drug was larger than the same proportion for the rest of drugs in that same group. If the 95% confidence interval of ROR was >1, this was taken as a signal for a higher risk of the given drug as compared to the average of the respective group.
Gabapentin, sertraline, citalopram, lithium, and amisulpride had a signal for the ROR to be increased above 1 within their respective groups. Bupropion, desvenlafaxine, duloxetine, escitalopram, and paroxetine had ROR values <1. For all other drugs, 1 was within the ROR confidence interval.
For gabapentin and lithium, the analysis of RORs confirmed case reports and cautionary lists. For a number of antidepressant drugs associated with a higher-than-average risk, no case reports exist substantiating our results. For these drugs, special attention should be paid to this risk. The remarkable difference between citalopram and escitalopram could prompt experimental work to confirm differential influence of the two preparations on neuromuscular transmission.
许多药物可使重症肌无力症状恶化。临床医生通常依赖于根据病例报告编制的警示清单。我们旨在为抗癫痫药、抗抑郁药、抗精神病药和镇静药这几组药物的风险比较提供定量依据。
我们从世界卫生组织药物警戒数据库中提取了这些组内药物的不良反应(ADR)计数(总数和与重症肌无力相关的计数),并计算了药物组内的报告比值比(ROR)。对于给定药物,如果该药与重症肌无力相关的 ADR 比例大于同一组中其他药物的相同比例,则该药物的 ROR 会增加超过 1。如果 ROR 的 95%置信区间>1,则认为该药物的风险高于相应组的平均值。
加巴喷丁、舍曲林、西酞普兰、锂和氨磺必利在各自的组内均存在 ROR 增加的信号。安非他酮、去甲文拉法辛、度洛西汀、依西酞普兰和帕罗西汀的 ROR 值<1。对于其他所有药物,1 在 ROR 置信区间内。
对于加巴喷丁和锂,ROR 分析证实了病例报告和警示清单。对于一些与平均风险较高相关的抗抑郁药,没有病例报告证实我们的结果。对于这些药物,应特别注意这一风险。西酞普兰和艾司西酞普兰之间的显著差异可能会促使进行实验工作以确认两种制剂对神经肌肉传递的不同影响。