title: Dependence and withdrawal reactions to benzodiazepines and selective serotonin reuptake inhibitors. How did the health authorities react?
abstract: OBJECTIVE
  Our objective was to explore communications from drug agencies about benzodiazepine dependence and selective serotonin reuptake inhibitors (SSRIs) withdrawal reactions over time.
  
  
  METHODS
  Documentary study. We searched the web-sites of the European Medicines Agency and the drug agencies in USA, UK, and Denmark for documents mentioning benzodiazepines or SSRIs. We supplemented with other relevant literature that could contribute to our study. The searches were performed in 2009 in PubMed, Google, BMJ and JAMA.
  
  
  RESULTS
  It took many years before the drug regulators acknowledged benzodiazepine dependence and SSRI withdrawal reactions and before the prescribers and the public were informed. Drug regulators relied mainly on the definitions of dependence and withdrawal reactions from the diagnostic psychiatric manuals, which contributed to the idea that SSRIs do not cause dependence, although it is difficult for many patients to stop treatment. In the perspective of a precautionary principle, drug agencies have failed to acknowledge that SSRIs can cause dependence and have minimised the problem with regard to its frequency and severity. In the perspective of a risk management principle, the drug agencies have reacted in concordance with the slowly growing knowledge of adverse drug reactions and have sharpened the information to the prescribers and the public over time. However, solely relying on spontaneous reporting of adverse effects leads to underestimation and delayed information about the problems.
  
  
  CONCLUSIONS
  Given the experience with the benzodiazepines, we believe the regulatory bodies should have required studies from the manufacturers that could have elucidated the dependence potential of the SSRIs before marketing authorization was granted.
authors.affiliation: The Nordic Cochrane Centre, Department 7811, Rigshospitalet, Blegdamsvej, Copenhagen, Denmark.
authors.forename: Margrethe
authors.initials: M
authors.lastname: Nielsen
authors.forename: Ebba Holme
authors.initials: EH
authors.lastname: Hansen
authors.forename: Peter C
authors.initials: PC
authors.lastname: Gøtzsche
mesh_terms: D001569:Benzodiazepines / Q000009:adverse effects* / Q000266:history; D005062:European Union; D049673:History, 20th Century; D006801:Humans; D007880:Legislation, Drug; D017367:Selective Serotonin Reuptake Inhibitors / Q000009:adverse effects* / Q000266:history; D013375:Substance Withdrawal Syndrome / Q000209:etiology* / Q000266:history / Q000523:psychology; D019966:Substance-Related Disorders / Q000209:etiology*; D014481:United States
chemical_list: D001569:Benzodiazepines; D017367:Selective Serotonin Reuptake Inhibitors