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Migraine & Depression: The newest info about serotonin syndrome

Medical professionals and patient advocates have been educating Migraine patients for a few years now about the risk of developing a dangerous, but rare condition called serotonin syndrome. But the number of actual cases has been difficult to pin down.

Researchers at the June 2013 International Headache Congress, a joint conference of the International Headache Society and American Headache Society, presented reassuring new research about the frequency of serotonin syndrome.

Serotonin is a chemical found in the brain. Triptans, a type of medication that treat Migraine attacks, and antidepressants, which are used for management of depression and Migraine prevention, both release serotonin. Rarely, when a patient is taking both types of medications, serotonin levels can become dangerously high.

The research team that presented in June reviewed patient data collected between 2001 and 2010 in an effort to determine the true risk to patients. This data showed very few cases of serotonin syndrome among patients taking a combination of these serotonin raising medications.


By way of reference, back in July 2006, the Food & Drug Administration (FDA) issued a warning about the possibility that patients taking both a triptan and an antidepressant were at risk of experiencing serotonin syndrome. At the time the FDA asked manufacturers of triptans and antidepressants to update package labeling to warn users of this risk.

In 2010, the American Headache Society published a position paper about serotonin syndrome in the journal Headache. In this paper the AHS said there was insufficient evidence of serotonin syndrome risk to limit the use of triptans alone or triptans combined with antidepressants. The authors of this position paper reviewed both available literature and the FDA adverse events registry in forming the organization’s official position.

Current View

The researchers who presented in June said it may be unnecessary for patients using one category of medication to avoid use of the other category. Further, reinforcing the view of the 2010 AHS position paper, they said the data suggests automatic warning labels regarding serotonin syndrome may be unnecessary. Finally, these researchers believe the 2006 FDA serotonin syndrome warning should be reconsidered.

Given that Migraine patients are more likely than other people to deal with depression, Migraine patients avoiding triptans because they use an antidepressant or avoiding antidepressants because they use triptans is a very real concern. This is especially worrisome if the risk of serotonin syndrome is as low as we now believe it to be.

Use of triptans can be an import component of good Migraine disease management, which we know can prevent transformation from episodic to Chronic Migraine. Antidepressants can be an essential aspect of good depression management, too.

Empower Yourself

While serotonin syndrome is rare, it’s important to familiarize yourself with the symptoms now so you can seek immediate medical attention if you think you’re dealing with it. It’s an extremely serious condition, so the sooner you seek treatment the better. With this kind of condition, it’s definitely better to err on the side of caution by seeking medical treatment. Please don’t even worry about falling into the trap of feeling silly if you happen to be wrong.

These are some of the common symptoms of serotonin syndrome:

  • Confusion
  • Agitation
  • Blood pressure changes
  • Body temperature changes
  • Rapid pulse
  • Muscle twitches
  • Gastrointestinal issues, such as nausea, vomiting and/or diarrhea
  • Shivering
  • Sweating
  • Coordination issues

It’s also essential, as always, to let all your health care providers know about everything you’re taking, including herbs and supplements. Some herbs and supplements can raise serotonin levels, too, not just prescription medications.

What questions do you have about serotonin syndrome? Please share them in the comments.

This article represents the opinions, thoughts, and experiences of the author; none of this content has been paid for by any advertiser. The team does not recommend or endorse any products or treatments discussed herein. Learn more about how we maintain editorial integrity here.

  1. Paul Rizzoli, Rebecca Burch, Brian Wainger, Carolyn Bernstein, Elizabeth Loder. "The Risk of Serotonin Syndrome with Concomitant Use of Triptan Antimigraine Drugs and SSRI/SNRI Antidepressants: A Population-Based Surveillance Study."Cephalalgia 33(8 Supplement) 1–291. DOI: 10.1177/0333102413490487.
  2. Randolph W. Evans, Stewart J. Tepper, Robert E. Shapiro, Christina Sun-Edelstein, Gretchen E. Tietjen. "The FDA Alert on Serotonin Syndrome With Use of Triptans Combined With Selective Serotonin Reuptake Inhibitors or Selective Serotonin-Norepinephrine Reuptake Inhibitors: American Headache Society Position Paper." Headache 2010;50:1089-1099. doi: 10.1111/j.1526-4610.2010.01691.x.
  3. Serotonin Syndrome. Medline Plus. ONLINE. Available: [8 July 2012].


    6 years ago

    I am grateful to see an article here on serotonin syndrome. I have suffered from horrid headaches… Not migraines… When I am given certain medications after they wear off. While I also take 6-7 meds for chronic migraines, I also have MS and take a few more for that fun issue too,… plus I have been on/off antidepressants. (Funny, I have a difficult time finding one since most new ones give me these headaches! Now I know why!).
    However I have learned that meds with codeine or any powerful narcotic-type additive will give me a worse head afterwards for weeks than any pain it was intended to help. (The first drug they offered after my 4 knee surgeries!). Some ergots do also. I take Imitrex often and need that to be a priority med. So any new med that the Imitrex doesn’t like, gets dumped.
    I keep a running list of these meds along with my usual allergic list and the pre-typed arm-length one of all meds I currently take! Whew!

  • lauren
    6 years ago

    How does Topamax figure into this? Like many of us, I take a whole pharmacopia of drugs, and we keep trying to cut back dosages to see how I do.

    At one point, just before I went in for hand surgery in October, my blood pressure went up and would not come down–couldn’t affect it with meditation as I had before–though it never had gotten very high anyway. The day I went in for surgery, however, it was fine. After that we started titrating down the Topamax (for other reasons) and I haven’t had trouble since.

    There must be many paths to migraines–antidepressants never seemed to prevent them for me. But then how is one to know?

  • Ninotores
    6 years ago

    Yeah, I don’t take any medications for my migraines and the symptoms of serotonin syndrome sound like a typical migraine prodrome to me. Are migraines brought on by spikes in serotonin levels followed by an abrupt drop? Is that why triptans work to alleviate the headaches and antidepressants help to prevent them?

  • zippy36
    6 years ago

    I was taking Cymbalta which was fine until I started receiving a higher dosage. It landed me in the emergency room with a severe migraine and out of control blood pressure. I have never had high blood pressure before!! It was believed I had serotonin syndrome.

  • tucker
    6 years ago

    There are more interactions than just the triptans and antidepressants. I take a ridiculous amount of medications and if there is a new pharmacist subbing in, I always have to talk to them about something I get refilled. The biggest ones that come up for me are generic reglan with anything, but the imitrex injection or maxalt tabs/mirtazipine came up once (and believe me – that mirtazapine turned my migraines around so I’ll take my chances!) I think tramadol is another kicker as well as ondansetron? The regular pharmacists know that my PCP is a good doc and the neuro is keeping up with my cardiology stuff and I try to look everything up too. I’m just praying for the day I can stop all this stuff!

  • mountainiris
    6 years ago

    This was a very interesting article, but naturally I’m full of questions now! Can a person, specifically a migraine patient, suffer from serotonin syndrome without having used the triptans? Meaning, is it possible to have your serotonin levels out of whack JUST from antidepressant medications or from antidepressants and other types of medications? I have not been able to used triptans since Imitrex first came on the market as a self-injectable many years ago. It was a “wonder drug” for me at first but eventually the side effects (chest pressure, rapid pulse, throat tightness, breathing difficulty, etc.) became worse than the migraine itself! So, I have avoided all triptans ever since and am too scared to try any variation.

    After reading this article this morning, I have so many of the “symptoms” listed for the serotonin syndrome, that now I’m wondering why my doctors haven’t picked up on this previously. I see my general practitioner on about a monthly basis, I see my neurologist about every 6 weeks, and I have a pain specialist that I see every 2-3 months. I have fibromyalgia and have had a rough year medically which has kept me from working for the past 9 months. I will be mentioning this to them on my next visits, but I’m afraid that what I mention will be taken lightly and not really considered. Any advice?

  • shine4him
    6 years ago

    My mom has the same reaction to Imitrex, but we’ve started cutting our pills in half and it still works, but cuts back on the side effects. Maybe talk with your doctor about dosage levels if you want to try other triptans. It may be just the amount you got that was causing such a rough reaction.

  • Melissa Ravens
    6 years ago

    I too have the same reaction to Imetrex. I can’t take it under any circumstance. However, I have no problems with the other triptans, such as Frova, Maxalt and Relpax. You may want to ask your Neuro. for samples. Or just bring it up to him and see what he thinks.

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