An exploratory approach to the serotonin syndrome: an update of clinical phenomenology and revised diagnostic criteria

Med Hypotheses. 2000 Sep;55(3):218-24. doi: 10.1054/mehy.2000.1047.


Serotonin-related adverse side-effects of psychotropic drugs were first recorded in humans in 1960. However, since 1991, these related cases have been diagnosed as 'serotonin syndrome (SS)' according to the criteria reported by Sternbach. In this article, we have reviewed and further explored the validity of these criteria. The clinical profile of 24 cases of the SS published between 1991 and 1995 has been analysed in detail and compared with the symptomatology of 38 previous cases which were also further analysed. Mainly Medline and references from other reports were used to review these cases. The general concept put forward by Sternbach has been approved. On the basis of the severity of overall clinical presentation, it appeared that there is a need to further classify SS into three main groups as: (1) mild state of serotonin-related symptoms; (2) serotonin syndrome (full-blown form); (3) toxic states. Furthermore, the detailed analysis of the SS cases published so far suggests that 'the diagnostic criteria for SS' also require further revision, and these are presented here. We also review, present and discuss the guidelines for the management and treatment of SS.

MeSH terms

  • Humans
  • Practice Guidelines as Topic
  • Psychotropic Drugs / adverse effects
  • Serotonin Agents / adverse effects
  • Serotonin Syndrome / diagnosis*
  • Serotonin Syndrome / drug therapy
  • Serotonin Syndrome / physiopathology


  • Psychotropic Drugs
  • Serotonin Agents