What is the difference between dependence and withdrawal reactions? A comparison of benzodiazepines and selective serotonin re-uptake inhibitors

Addiction. 2012 May;107(5):900-8. doi: 10.1111/j.1360-0443.2011.03686.x. Epub 2012 Jan 23.


Aims: To explore the rationale for claiming that benzodiazepines cause dependence while selective serotonin re-uptake inhibitors (SSRIs) do not.

Methods: We analysed the definitions of dependence and withdrawal reactions as they had appeared over time in the Diagnostic Statistical Manual of Mental Diseases (DSM) and the International Classification of Diseases (ICD). We also compared the discontinuation symptoms described for the two drug groups in a systematic review.

Results: The definition of substance dependence has changed over time in both the DSM and ICD. In the most recent classifications several criteria, including behavioural, physiological and cognitive manifestations, must be fulfilled. This change was published with the revision of the DSM-III revision in 1987 (DSM-IIIR), after the recognition of benzodiazepine dependence and just before the SSRIs were marketed in 1987-88. We found that discontinuation symptoms were described with similar terms for benzodiazepines and SSRIs and were very similar for 37 of 42 identified symptoms described as withdrawal reactions.

Conclusions: Withdrawal reactions to selective serotonin re-uptake inhibitors appear to be similar to those for benzodiazepines; referring to these reactions as part of a dependence syndrome in the case of benzodiazepines, but not selective serotonin re-uptake inhibitors, does not seem rational.

Publication types

  • Comparative Study
  • Review
  • Systematic Review

MeSH terms

  • Benzodiazepines / adverse effects*
  • Diagnosis, Differential
  • Diagnostic and Statistical Manual of Mental Disorders
  • Humans
  • International Classification of Diseases
  • Selective Serotonin Reuptake Inhibitors / adverse effects*
  • Substance Withdrawal Syndrome / diagnosis
  • Substance Withdrawal Syndrome / etiology
  • Substance-Related Disorders / diagnosis
  • Substance-Related Disorders / etiology*
  • World Health Organization


  • Serotonin Uptake Inhibitors
  • Benzodiazepines