The U.S. Food and Drug Administration (FDA) in 2006 issued a public health advisory warning that a life-threatening condition called serotonin syndrome may result when a class of headache medications called triptans is used together with a selective serotonin and norepinephrine reuptake inhibitor (SSNRI) or a selective serotonin reuptake inhibitor (SSRI). The condition involves excessive amounts of the brain chemical serotonin.  However, research indicates that this very rarely occurs.

Other substances that may contribute to serotonin syndrome include monoamine oxidase inhibitors (MAOIs), meperidine (an opioid painkiller), dextromethorphan (cough medicine) or illegal drugs such as ecstasy or LSD, according to the National Institutes of Health (NIH). There are also reports that St. John’s wort, an herbal supplement taken by some people to relieve depression, may contribute to serotonin syndrome.

Symptoms of serotonin syndrome can include restlessness, hallucinations, incoordination, fast heartbeat (tachycardia), rapid changes in blood pressure, increased body temperature, overactive reflexes, nausea, vomiting and diarrhea. The FDA advises that patients consult their physician before stopping their medications. People experiencing serotonin syndrome should be hospitalized under close observation for at least 24 hours, according to the NIH.

Patients should consult their physician before taking any additional prescriptions, over-the-counter medications, supplements or herbal substances, especially St. John’s wort.

Of particular concern to individuals taking tricyclic antidepressants (TCAs), which have the longest history of use in pain management among antidepressants, are:

• Allergy, asthma, hay fever or cold medications, including antihistamines, bronchodilators and decongestants
  
  
• Amphetamines or other diet pills
  
  
• Antihypertensives including clonidine, guanadrel, guanethidine, methyldopa, metyrosine and rauwolfia alkaloids
  
  
• Antipsychotics
  
  
• Central nervous system depressants
  
  
• MAOIs or SSNRIs
  
  
• Thyroid medications
  
  
• Cimetidine (antiulcer drug)
  
  
• Metoclopramide (antiemetic and gastrointestinal stimulant)
  
  
• Pemoline (central nervous system stimulant)
  
  
• Pimozide (Tourette’s syndrome medication)

With SSNRIs, a major drug interaction of concern besides triptans is MAOIs. In patients taking an SSNRI and an MAOI, there have been reports of serious and sometimes fatal reactions including hyperthermia, rigidity, myoclonus (muscle twitches and jerking), changes in autonomic functions such as blood pressure and heart rate, and changes in mental status such as severe agitation worsening to coma.

Other potential drug interactions with SSNRIs include TCAs, SSRIs, quinolone antibiotics and certain antiarrhythmics.