When talking about triptans used for migraines such as Zolimitriptan, such drugs are selective serotonin receptor agonists.

SSRIs, as their function states, are Selective Serotonin Reuptake Inhibitors.

The British National Formulary doesn't say so, but I am wondering if triptans can affect the efficacy of SSRIs. If so, how?

From the way I understand it, triptans could help boost the efficacy of SSRIs due to the fact that

  1. the SSRIs are blocking ("inhibiting") reuptake of serotonin, meaning more serotonin is available to pass further messages between nearby nerve cells.


  1. the triptans activate serotonin receptors being that they are an agonist (a chemical that binds to a receptor and activates the receptor to produce a biological response).

Am I correct?


1 Answer 1


triptans could help boost the efficacy of SSRIs

There is minimal evidence for this Chris. One of the reasons for that is that there is a limit to how much serotonin is released for the nerve cell. So more of the same isn't going to make much difference. edit: So in terms of reuptake inhibitors, triptans are agonists. So increased agonism seems unlikely to make a significant difference.

Theoretically there is a risk of serotonin syndrome. There has been many case reports and a black label FDA warning has been issued in the 1990s.However the data for that severe reaction seems to be patchy and the rates of co-prescription of SSRIs and triptans have not reduced or changed in any meaningful way.


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    $\begingroup$ "there is a limit to how much serotonin is released for the nerve cell" - SSRIs don't directly affect serotonin release, they prevent reuptake (so it just lingers in the extracellular space in and around the synapse). Similarly, triptans don't boost release of serotonin, they are themselves agonists at serotonin receptors, binding the same place as serotonin. So, one would expect that both would be competing for available receptors. Their effects likely sum, but from mechanism you wouldn't expect synergy. It gets complicated and hard to predict due to changes in receptor expression, however. $\endgroup$
    – Bryan Krause
    Commented Nov 21, 2019 at 17:06

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