Daily and prolonged intake of high doses of triptan medications (sumatriptan, or Imitrex, rizatriptan, or Maxalt, eletriptan, or Relpax and 4 others) has been shown to be safe in at least three clinical reports. I also have a few patients who have good control of their headaches and no side effects after many years of taking high doses of triptans daily. (I am not suggesting that it is healthy to take any medicine daily for years, but some people have no other choice because without this treatment they are disabled). A report just published in The Journal of Clinical Pharmacy and Therapeutics describes a patient who also was taking high doses of triptans daily (zolmitriptan or Zomig and frovatriptan or Frova tablets and sumatriptan injections), but who developed severe depression on two occasions when the triptans were stopped suddenly. The first bout of depression was very difficult to treat despite trials of several antidepressant drugs (amitriptyline, or Elavil, mirtazapine, or Remeron, and duloxetine, or Cymbalta, with addition of quetiapine, or Seroquel). All these antidepressants work through the serotonin system. His second bout of depression responded very well to bupropion (Wellbutrin), an antidepressant that works on norepinephrine and dopamine, rather than serotonin. This report suggests that while it may be safe to take triptans daily for a long time, they can affect the serotonin mechanisms in the brain and that they should never be stopped suddenly. Another important lesson is that if depression does develop after stopping daily triptans, the preferred drug may be bupropion.