PMID- 35462924
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20221128
IS  - 1663-9812 (Print)
IS  - 1663-9812 (Electronic)
IS  - 1663-9812 (Linking)
VI  - 13
DP  - 2022
TI  - Neurological Adverse Events Associated With Esketamine: A Disproportionality 
      Analysis for Signal Detection Leveraging the FDA Adverse Event Reporting System.
PG  - 849758
LID - 10.3389/fphar.2022.849758 [doi]
LID - 849758
AB  - Esketamine was approved for the treatment of treatment-resistant depression in 
      2019. After the approval of esketamine, numerous concerns have been raised 
      regarding its long-term safety and tolerability. A previous systematic 
      pharmacovigilance study on esketamine-related adverse events (AEs) was published 
      in 2020; however, it has not been updated 2 years later. The primary aim of this 
      study was to detect and characterize neurological safety signals of esketamine to 
      partially update the knowledge in this field using the FDA pharmacovigilance 
      database. Reporting odds ratio (ROR) was calculated for esketamine-related 
      neurological AEs from 2019 to 2021 with a signal considered when the lower limit 
      of the 95% confidence interval (CI) of ROR (ROR(025)) exceeded one. Severe and 
      non-severe cases were compared using an independent samples t-test or chi-squared 
      (chi2) test, and a rating scale was used to prioritize the signals. The database 
      contained 720 cases of esketamine-associated neurological AEs, with 21 signals 
      detected, ranging from a ROR(025) of 1.05 (disturbance in attention) to 204.00 
      (sedation). 16 latest neurological AEs emerged in the second year of marketing 
      approval of esketamine, with eight signals detected. The associations between 
      esketamine and nervous system disorders persisted when stratifying by sex, age, 
      and reporter type, whereas the spectrum of neurological AEs differed in 
      stratification regimens. Esketamine dosage, antidepressant polypharmacy, or 
      co-prescription with benzodiazepines affected AEs severity (t = 2.41, p = 0.017; 
      chi2 = 6.75, p = 0.009; and chi2 = 4.10, p = 0.043; respectively), while age and sex 
      did not (p = 0.053 and p = 0.397, respectively). Three signals were categorized 
      as moderate clinical priority [i.e., sedation, dizziness, and dysgeusia (priority 
      points 7, 5, and 5, respectively)], showing the same early failure type profiles. 
      Notably, seven detected disproportionality signals were not previously detected 
      in clinical trials. Although the majority of results were in line with those 
      obtained in the previous study, there were discrepancies in the spectrum of 
      neurological AEs and the effects of several risk factors on AEs severity among 
      the two studies that should be recognized and managed early in clinical 
      treatments.
CI  - Copyright (c) 2022 Guo, Wang, Yuan, Wu, Liu, He and Wang.
FAU - Guo, Haoning
AU  - Guo H
AD  - Division of Psychopharmacology, Department of Pharmacy, The Third People's 
      Hospital of Mianyang, Sichuan Mental Health Center, Mianyang, China.
FAU - Wang, Bin
AU  - Wang B
AD  - Clinical Experimental Center, Jiangmen Central Hospital, Affiliated Jiangmen 
      Hospital of Sun Yat-sen University, Jiangmen, China.
FAU - Yuan, Shuying
AU  - Yuan S
AD  - Division of Psychopharmacology, Department of Pharmacy, The Third People's 
      Hospital of Mianyang, Sichuan Mental Health Center, Mianyang, China.
FAU - Wu, Silin
AU  - Wu S
AD  - Division of Psychopharmacology, Department of Pharmacy, The Third People's 
      Hospital of Mianyang, Sichuan Mental Health Center, Mianyang, China.
FAU - Liu, Jing
AU  - Liu J
AD  - Department of Pathology, The Third People's Hospital of Mianyang, Sichuan Mental 
      Health Center, Mianyang, China.
FAU - He, Miaoquan
AU  - He M
AD  - Division of Psychopharmacology, Department of Pharmacy, The Third People's 
      Hospital of Mianyang, Sichuan Mental Health Center, Mianyang, China.
FAU - Wang, Jisheng
AU  - Wang J
AD  - Division of Psychopharmacology, Department of Pharmacy, The Third People's 
      Hospital of Mianyang, Sichuan Mental Health Center, Mianyang, China.
LA  - eng
PT  - Journal Article
DEP - 20220408
PL  - Switzerland
TA  - Front Pharmacol
JT  - Frontiers in pharmacology
JID - 101548923
EIN - Front Pharmacol. 2022 Nov 09;13:1075966. PMID: 36438806
PMC - PMC9023790
OTO - NOTNLM
OT  - FAERS
OT  - disproportionality analysis
OT  - esketamine
OT  - neurological adverse events
OT  - pharmacovigilance
OT  - signal
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2022/04/26 06:00
MHDA- 2022/04/26 06:01
PMCR- 2022/04/08
CRDT- 2022/04/25 05:13
PHST- 2022/01/06 00:00 [received]
PHST- 2022/03/21 00:00 [accepted]
PHST- 2022/04/25 05:13 [entrez]
PHST- 2022/04/26 06:00 [pubmed]
PHST- 2022/04/26 06:01 [medline]
PHST- 2022/04/08 00:00 [pmc-release]
AID - 849758 [pii]
AID - 10.3389/fphar.2022.849758 [doi]
PST - epublish
SO  - Front Pharmacol. 2022 Apr 8;13:849758. doi: 10.3389/fphar.2022.849758. 
      eCollection 2022.