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 brainstem). The altered activity of this messenger protein has been implicated in both migraine and depression. 

Medicines that modify serotonin levels can be effective in treating both disorders. Such medication for migraine includes, “triptans”: e.g., Sumatriptan (Armstrong, S.C. and Cozza, K.L., 2002).

For depression drug belong to category of the selective serotonin reuptake inhibitors (SSRIs) and selective serotonin/norepinephrine reuptake inhibitors (SNRIs); e.g., Fluoxetine, Citalopram, Paroxetine for the SSRIs, and Venlafaxine for the SNRIs (Homberg, J.R., Schubert, D. and Gaspar, P., 2010).

Since migraine can overlap with depression as both the mental issues occur frequently in the individuals. So, one can think of prescribing these two medicines in combination. But is this combined therapy safe to administer?

Is Combined Therapy Of Sumatriptan And Fluoxetine Safe?

Migraine headaches are very common in people suffering from anxiety and depression and vice-versa. That means there are millions of people who suffer from both the conditions.

In these conditions, doctors may prescribe SNRIs, SSRIs with triptans and Otc medication such as Sumatriptan with Naproxen or Sumatriptan with Tylenol.  Similar therapy of drugs includes the combination of sumatriptan and fluoxetine.

Both of these drugs cause an increase in serotonin level because of which the potential of their interaction is considerable. It is observed that the combination of these two drugs lead to a rare but serious condition called serotonin syndrome (Wenzel, R.G., Tepper, S., Korab, W.E. and Freitag, F., 2008).

This syndrome is caused due to the transmission of excess serotonin in the brain. In case of    any symptoms of syndrome observed, seek immediate medical attention as it can be treated with prompt diagnosis and treatment but It could become fatal if left untreated.

As per the reports from different researchers, it is concluded that the risk of serotonin syndrome is very rare in people who undergo this combined therapy or in other co-prescribed triptans and SSRI or SNRI antidepressants i.e. it ranges from 0-4 cases per 10,000 person-years.

It can be therefore concluded that the combined use of sumatriptan and fluoxetine may be  safe, if taken under supervision of a doctor and in a prescribed manner.

Signs And Symptoms Of Serotonin Syndrome

One of the causes of the occurrence of Serotonin syndrome is intake of medication or combination of medications that boost the serotonin level to a greater extent.

This can be treated with prompt diagnosis and treatment. There is no such laboratory test for this syndrome but can be identified through medical history and physical symptoms, which are-

  1. Hyperthermia
  2. Rhabdomyolysis
  3. Kidney failure
  4. Breathing difficulty/ failure
  5. Seizures
  6. Metabolic acidosis
  7. Blood clots
  8. Seizures
  9. Change in blood pressure
  10. Tachycardia
  11. Hallucination
  12. Shivering, shaking
  13. Confusion
  14. Restlessness
  15. Vomiting, diarrhea

The outlook of some symptoms could be fatal/ life-threatening, which usually happens within 24 hours. In mild cases of syndrome, doctors may advise to stop the medication which was causing the problem but in case of severe symptoms, you will have to visit the hospital and seek surveillance from the healthcare professional (Bodner, R.A., Lynch, T., Lewis, L. and Kahn, D., 1995).

Who Should Not Try Sumatriptan With Fluoxetine?

Sumatriptan and fluoxetine both are well-tolerated drugs when taken alone but in case of combined therapy, FDA has warned the possibility of serotonin syndrome when the triptans and SNRIs and SSRIs are taken in combination. 

In 2006 FDA received 27 reports of serotonin syndrome in patients who were consuming the combination of sumatriptan and fluoxetine (SSRI and SNRI). This combination treatment has potential adverse reactions which might not be tolerated by an individual who is suffering from renal disorder or has difficulty in breathing, increased heart rate or balance disorder.

This combination should only be taken after consulting with the medical professional as he would recommend therapy on the basis of medication history and physical symptoms. 


Sumatriptan is a well-known drug specifically for migraine headache and fluoxetine is prescribed in depression and anxiety. Both these disorders are associated with each other, thus, doctors can prescribe SNRIs and SSRIs with triptans. 

This drug combination can cause a rare but serious disease serotonin syndrome which is a type of poisoning as its outcome could be fatal, symptoms of which are usually seen within 24 hours of administration.

If a person does not experience any symptom after 6-8 hours of drug exposure, then this combination is considered safe but prescription should be mandatorily presented. As this combination can give you a small but life long side effect.



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