Triptans, SSRIs and Serotonin Syndrome

In 2006, the US Food and Drug Administration (FDA) a warning regarding a possible life-threatening risk of serotonin syndrome when triptans are used in combination with a selective serotonin reuptake inhibitor (SSRI) or a selective serotonin/norepinephrine reuptake inhibitor ( SNRI) can be used (1). These are two groups of special antidepressants. This warning was based on 29 case reports. In addition, 11 further case reports of patients with serotonin syndrome who were treated with monotherapy with selective SSRIs and one case report in which serotoninergic agents were combined were published (2-9). The case reports are purely observations for which there were no controls regarding the causal relationship. A causal connection between combination therapy and the possible occurrence of serotonin syndrome cannot therefore be proven based on the data. Of the 29 cases the FDA based its warning on, only 10 actually met the diagnostic criteria for serotonin syndrome. However, none of the patients met the criteria for serotonin toxicity. Based on this database, Evans et al. 2010 (5) concluded that there were no adequate data to determine a possible risk of serotonin syndrome from the combination of a triptan with an SSRI/SNRI or with triptan monotherapy. The current data does not justify a limitation on the use of a triptan together with an SSRI or an SNRI or even triptan monotherapy. However, physicians should generally be alert to possible symptoms of serotonin syndrome given the seriousness of this complication (5).

A recent study examined the combined use of triptans and SSRIs or SNRIs (6). US data for the period 2007 to 2008 and for the period 2003 to 2004 were compared. In the period 2007 to 2008, an average of 5,256,958 patients were prescribed a triptan annually. In 2003 to 2004, an average of 3,874,367 received a triptan. There was an increase in prescriptions of 35.7%. On average, 68,603,600 patients received a prescription for an SSRI or an SNRI in the years 2007 to 2008. On average, 50,402,149 patients were prescribed a corresponding medication in the years 2003 to 2004. This represents an increase in prescriptions of 36.1%. On average, 1,319,763 patients received a triptan together with an SSRI or an SNRI between 2007 and 2008. Corresponding prescriptions were prescribed for an average of 694,276 patients between 2003 and 2004. This represents a 90.1% increase in prescriptions.

Experts have criticized the decision of the FDA with regard to the warning of a joint use of a tripan and a SSRI or a Snri (2-9). As explained above, this criticism is based on a very small case series of 29 patients, in whom only 10 had the criteria of serotonin syndrome and, in no way, the criteria of serotonin toxication could not be validated. The currently published figures for the combined use of triptans and SSRI or Snri show that doctors consider the risk of serotonin syndrome to be negligible by combining a tripan with an antidepressant. To date, there is no reliable figures about the possible formation of serotonin syndrome due to the joint use of triptans and SSRI or Snri.

It can be concluded that a possible risk of serotonin syndrome if triptans are used in combination with a selective serotonin-reuptake inhibitor (SSRI) or a selective serotonin/norepinephrin reuptake inhibitor (SNRI) not to be proven or quantified with scientific data. From our own experience for the use of triptans over a period of more than 20 years, it can be found that in no way a serotonin syndrome has been observed in any case with the use of triptans or antidepressants. The same also applies to the use of a tripan as monotherapy.

1.FDA