PMID- 32418024
OWN - NLM
STAT- MEDLINE
DCOM- 20210422
LR  - 20210422
IS  - 1432-1041 (Electronic)
IS  - 0031-6970 (Linking)
VI  - 76
IP  - 8
DP  - 2020 Aug
TI  - Paradoxical adverse drug reactions: descriptive analysis of French reports.
PG  - 1169-1174
LID - 10.1007/s00228-020-02892-2 [doi]
AB  - INTRODUCTION: Paradoxical adverse drug reactions (ADRs) are defined as being 
      opposing reactions to the pharmacological effect of drugs in relation to its 
      pharmacodynamic properties. Their diagnosis is difficult as they are relatively 
      rare with atypical clinical presentation (with the possibility of being confused 
      with drug ineffectiveness or the worsening of the underlying disease). This kind 
      of ADR may be particularly subject to under-notification. The aim of the present 
      study is to describe paradoxical ADRs using the French PharmacoVigilance DataBase 
      (FPVDB). METHOD: We analysed all reports recorded in the FPVDB with drugs defined 
      as "suspect" and which included the term "paradoxical reaction" (PR) (according 
      to MedDRA classification) from 01/01/1984 to 12/31/2018. The drugs were 
      classified according to the Chemical Therapeutic Anatomical Classification (ATC). 
      RESULTS: We found 57 reports of PR, with half of them recorded between 2015 and 
      2018. The median age of patients was 46 years, mainly male (54%). The most 
      frequently involved drugs were immunomodulating agents (n = 28, 49%) and 
      psychotropics (n = 28, 49%). The leading paradoxical ADRs were psychiatric 
      (anxiety, sleep and behavioural disorders) and skin-related. In 19 cases (33%), 
      PR was related to benzodiazepines mainly occurring in patients in extreme ages 
      (five cases in children and patients > 70, respectively, 53%). For 
      psychotropic-induced PR (n = 28), known contributory factors (alcohol 
      consumption, underlying psychiatric diseases) were found in 18 cases (64%). 
      Paradoxical reactions with immunomodulating agents were mainly related to skin 
      ADRs (n = 25). For psychotropics, paradoxical ADRs occurred rapidly after a mean 
      delay of 1 day, predominantly following high doses. We also identified several 
      "unexpected" paradoxical reactions, such as cognitive degradation with donepezil, 
      or a return to impulsive smoking addiction with varenicline. CONCLUSION: This 
      study highlights that pharmacovigilance databases like the French database make 
      it possible to investigate the main characteristics of paradoxical reactions to 
      drugs. This ADR was mainly found in the FPVDB with psychotropic drugs and 
      immunomodulating agents. Moreover, pharmacovigilance databases enable the 
      identification of some signs of "unexpected paradoxical reactions". In order to 
      identify this type of ADR more effectively, work on awareness and harmonization 
      is required to register these reports. The addition of the term "paradoxical 
      reaction to the drug" to the list of other symptoms would facilitate their 
      identification and analysis.
FAU - Hakimi, Yan
AU  - Hakimi Y
AD  - Centre De Pharmacovigilance, De Pharmacoepidemiologie Et D'informations Sur Le 
      Medicament, Inserm UMR 1027, Faculte De Medecine, Centre Hospitalier 
      Universitaire, Toulouse, France.
FAU - Petitpain, Nadine
AU  - Petitpain N
AD  - Centre Regional De Pharmacovigilance-Service De Pharmacologie Clinique, 
      Toxicologie CHRU, De Nancy, France.
FAU - Pinzani, Veronique
AU  - Pinzani V
AD  - Departement De Pharmacologie Medicale et Toxicologie, Centre Regional De 
      Pharmacovigilance Occitanie-Est, Montpellier, France.
FAU - Montastruc, Jean-Louis
AU  - Montastruc JL
AD  - Centre De Pharmacovigilance, De Pharmacoepidemiologie Et D'informations Sur Le 
      Medicament, Inserm UMR 1027, Faculte De Medecine, Centre Hospitalier 
      Universitaire, Toulouse, France.
FAU - Bagheri, Haleh
AU  - Bagheri H
AUID- ORCID: 0000-0001-9585-9341
AD  - Centre De Pharmacovigilance, De Pharmacoepidemiologie Et D'informations Sur Le 
      Medicament, Inserm UMR 1027, Faculte De Medecine, Centre Hospitalier 
      Universitaire, Toulouse, France. haleh.bagheri@univ-tlse3.fr.
LA  - eng
PT  - Journal Article
DEP - 20200516
PL  - Germany
TA  - Eur J Clin Pharmacol
JT  - European journal of clinical pharmacology
JID - 1256165
SB  - IM
MH  - Adult
MH  - Adverse Drug Reaction Reporting Systems/statistics & numerical data
MH  - Aged
MH  - Databases, Factual
MH  - Drug-Related Side Effects and Adverse Reactions/*epidemiology
MH  - Female
MH  - France/epidemiology
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Pharmacovigilance
MH  - Young Adult
OTO - NOTNLM
OT  - Benzodiazepines
OT  - Drug safety
OT  - Immunomodulating agents
OT  - Paradoxical adverse drug reactions
OT  - Pharmacovigilance
EDAT- 2020/05/18 06:00
MHDA- 2021/04/23 06:00
CRDT- 2020/05/18 06:00
PHST- 2020/01/22 00:00 [received]
PHST- 2020/05/06 00:00 [accepted]
PHST- 2020/05/18 06:00 [pubmed]
PHST- 2021/04/23 06:00 [medline]
PHST- 2020/05/18 06:00 [entrez]
AID - 10.1007/s00228-020-02892-2 [pii]
AID - 10.1007/s00228-020-02892-2 [doi]
PST - ppublish
SO  - Eur J Clin Pharmacol. 2020 Aug;76(8):1169-1174. doi: 10.1007/s00228-020-02892-2. 
      Epub 2020 May 16.