Serotonin is a naturally occurring “messenger” protein that is found primarily in the gastrointestinal system, certain blood cells (platelets) and the central nervous system (brain and brain stem). Altered activity of this messenger protein has been implicated in both migraine and depression. Medications that modify serotonin can be effective in treating both disorders. Such medications include, for migraine, the “triptans”: eg, Sumatriptan; for depression, the selective serotonin reuptake inhibitors (SSRIs) and selective serotonin/norepinephrine reuptake inhibitors (SNRIs): eg, Fluoxetine, Citalopram, Sertraline, Paroxetine and others for the SSRIs, and Venlafaxine and others for the SNRIs.

Because migraine can often overlap with depression – each disorder occurs more frequently in individuals afflicted by the other condition than it does in the general population – many patients may be prescribed both a triptan (for acute migraine treatment) and an SSRI or SNRI (for chronic treatment of depression). The simultaneous administration of two drugs that promote serotonin’s activity theoretically could produce an acute overabundance of the protein and a constellation of symptoms termed “serotonin syndrome.”

This potential risk is something which will be flagged up by electronic prescribing systems, such as those used by GPs, as well as formulary such as the British National Formulary and Medicines Complete. However, clinically significant serotonin syndrome from simultaneous use of these medications appears to be extremely rare and many in the field believe that the evidence shows that this interaction is not even caused by the triptans at all. The benefit of adequate treatment for both migraine and depression appears to far outweigh the exceedingly low risk of dangerous “serotonin overload.”

The position statement from the National Migraine Centre is that if you are taking an antidepressant medication and your GP or specialist recommends a triptan medication (or vice versa) – this is a safe and widely used combination of medications and it’s not necessary to either change your antidepressant or choose a different type of medication for migraine pain relief.


This information is provided as a general guide only and is not a comprehensive overview of prescribing information. If you have any queries or concerns about your headaches or medications please discuss them with your GP or the doctor you see at the National Migraine Centre.