Chepke Craig, Shelton Richard, Sanacora Gerard, Doherty Teodora, Tsytsik Palina, Parker Nancy
Sandra & Leon Levine Psychiatry Residency Program at Atrium Health, Charlotte, North Carolina, USA.
Excel Psychiatric Associates, Huntersville, North Carolina, USA.
Int J Neuropsychopharmacol. 2024 Dec 1;27(12). doi: 10.1093/ijnp/pyae058.
Esketamine nasal spray (ESK) is approved, in conjunction with an oral antidepressant, for the treatment of treatment-resistant depression in adults and for the treatment of depressive symptoms in adults with major depressive disorder with acute suicidal ideation or behavior. No adverse events (AEs) of respiratory depression were reported in ESK phase 3 clinical trials; however, postmarketing incidents of respiratory depression associated with ESK use have been observed.
The Janssen Global Medical Safety (GMS) database was reviewed for cases meeting the criteria for respiratory depression with ESK using 47 months of postapproval data, based on the Standardized Medical Dictionary for Regulatory Activities (MedDRA) Query (SMQ) acute central respiratory depression (broad). FDA Adverse Event Reporting System (FAERS), EudraVigilance, and literature searches were performed to identify reports of respiratory depression related to ESK use.
Fifty cases, representing 50 patients, in the GMS database met the case definition for respiratory depression; 8 of these had a stronger association with ESK use. The MedDRA preferred term (PT) hypopnea met the threshold for disproportionality with ESK in FAERS. The MedDRA PTs asphyxia, oxygen saturation decreased, respiratory depression, and apnea met the threshold for disproportionality with ESK in EudraVigilance.
Despite extensive soliciting of AEs for ESK with the US Risk Evaluation and Mitigation Strategy program, respiratory depression is infrequently observed with ESK treatment in the postmarketing setting (estimated incidence: 1 case per 20 000 treatment sessions). Symptoms are manageable and resolve with minor supportive measures. Monitoring for symptoms of respiratory depression, including pulse oximetry, is recommended within the postdose observation period.
艾氯胺酮鼻喷雾剂（ESK）已获批与口服抗抑郁药联合使用，用于治疗成人难治性抑郁症以及治疗伴有急性自杀意念或行为的重度抑郁症成人患者的抑郁症状。在ESK的3期临床试验中未报告呼吸抑制的不良事件；然而，已观察到上市后与使用ESK相关的呼吸抑制事件。
使用47个月的批准后数据，基于监管活动标准化医学词典（MedDRA）查询（SMQ）急性中枢性呼吸抑制（广义），对杨森全球医学安全（GMS）数据库中符合ESK呼吸抑制标准的病例进行审查。进行了美国食品药品监督管理局不良事件报告系统（FAERS）、欧洲药品管理局药物警戒系统（EudraVigilance）检索以及文献检索，以识别与使用ESK相关的呼吸抑制报告。
GMS数据库中有50例病例（代表50名患者）符合呼吸抑制的病例定义；其中8例与ESK使用的关联性更强。MedDRA首选术语（PT）呼吸浅慢在FAERS中达到了与ESK不成比例的阈值。MedDRA PTs窒息、血氧饱和度降低、呼吸抑制和呼吸暂停在EudraVigilance中达到了与ESK不成比例的阈值。
尽管通过美国风险评估和缓解策略计划广泛征集了ESK的不良事件，但在上市后环境中，ESK治疗很少观察到呼吸抑制（估计发生率：每20000次治疗疗程1例）。症状可控，通过轻微的支持措施即可缓解。建议在给药后观察期内监测呼吸抑制症状，包括脉搏血氧饱和度监测。
