HSA would like to remind healthcare professionals of the potential risk of developing serotonin syndrome in patients taking 5-hydroxytryptamine receptor agonists (triptans) and Selective Serotonin Re-uptake Inhibitors (SSRIs) or Selective Norepinephrine Re-uptake Inhibitors (SNRIs). SSRIs are known to increase serotonin levels and possibly cause serotoinin syndrome when used concomitantly with serotonergic agents such as triptans.

In July 2006, the US Food and Drug Administration alerted healthcare professionals and the public of this potentially life-threatening interaction. The FDA reviewed 27 reports of serotonin syndrome reported from 1998 to 2002 in association with concomitant SSRI or SNRI and triptan use. Two cases were life-threatening and 13 required hospitalisation. It was found that some of the cases occurred in patients who had previously used both drugs concomitantly without experiencing serotonin syndrome.

The reported signs and symptoms of serotonin syndrome were highly variable and included respiratory failure, coma, mania, hallucinations, confusion, dizziness, hyperthermia, hypertension, sweating, trembling, weakness and ataxia. In eight cases, recent dose increases or addition of another serotonergic drug to an SSRI/triptan or SNRI/triptan combination were temporally related to symptom onset. The median time to onset of symptoms was one day, with a range of ten minutes to six days.

HSA has not received any local ADR reports associated with this interaction and serotonin syndrome. However, healthcare professionals are reminded to consider the following when prescribing SSRIs/SNRIs or triptans:

1. To weigh potential risk versus benefit of prescribing concomitant SSRI/SNRI and triptan therapy and discuss the possibility of serotonin syndrome with the patient when prescribing both concomitantly;
   
   
2. To keep in mind that triptans are often used intermittently and that SSRI, SNRI or triptan may be prescribed by a different healthcare professional;
   
   
3. To be alert to the highly variable signs and symptoms of serotonin syndrome. Serotonin syndrome symptoms may include mental status changes (e.g. agitation, hallucination, coma), automatic instability (e.g. tachycardia, labile blood pressure, hyperthermia), neuromuscular aberrations (e.g. hyperreflexia, incoordination) and/or gastrointestinal symptoms (e.g. nausea, vomiting, diarrhoea);
   
   
4. To observe patient on concomitant therapy carefully, particularly during treatment initiation and dose increases.
   
   Healthcare professionals are also encouraged to report suspected adverse reaction of this nature to the Pharmacovigilance Unit of HSA.
   

1. FDA public health advisory, July 2006. http://www.fda.gov/cder/drug/advisory/SSRI_SS200607.htm
   
   
2. Information for healthcare professionals – Venlafaxine (Effexor®), July 2006.   http://www.fda.gov/cder/drug/InfoSheets/HCP/venlafaxineHCP.htm