Medications and Serotonin Syndrome

Prozac, Paxil and Zoloft anti-depressant tablets, close-up
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According to the U.S. Food and Drug Administration, there is increased risk of serotonin syndrome as a result of combining selective serotonin reuptake inhibitors (SSRIs) and selective serotonin-norepinephrine reuptake inhibitors SSNRIs with migraine headache medications called triptans.

Selective Serotonin Reuptake Inhibitors (SSRIs)

It is believed that the brain contains several hundred different types of chemical messengers (neurotransmitters) that act as communication agents between different brain cells. Serotonin is a neurotransmitter that is important in regulating a variety of body functions and feelings. Low serotonin levels have been linked to depression and anxiety.

SSRIs inhibit the reuptake of serotonin in the brain. Reuptake is a process where neurotransmitters in the brain are reabsorbed and deactivated or recycled for future use. This causes an increase of serotonin levels, resulting in improved mood, decreased anxiety and inhibition of panic. SSRIs are considered the first-line treatment for panic disorder and include:

Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs)

SNRIs inhibit the reabsorption of serotonin and norepinephrine in the brain. Norepinephrine is a chemical messenger in the brain that influences sleep and alertness. It is believed to be correlated to the fight-or-flight stress response.

SNRIs include:

  • Cymbalta (duloxetine)
  • Effexor, Effexor XR (venlafaxine)


Triptans are a class of drugs commonly used to treat migraine or cluster headaches. They act on serotonin receptors in the brain, thereby affecting serotonin levels.

Examples of triptans include:

  • Amerge (naratriptan)
  • Axert (almotriptan)
  • Frova (frovatriptan)
  • Imitrex (sumatriptan)
  • Maxalt and Maxalt-MLT (rizatriptan)
  • Relpax (eletriptan)
  • Zomig and Zomig ZMT (zolmitriptan)

In addition to triptans, other classes of medications increase the risk of serotonin syndrome if used with SSRIs and SNRIs.

Tricyclic Antidepressants

Tricyclic antidepressants (TCAs) are named after the drugs’ “three-ringed” molecular structure. Prior to the introduction of SSRIs in the late 1980s, TCAs were the medication of choice for the treatment of major depressive disorder, panic disorder, and other anxiety disorders. TCAs are also used to treat certain pain syndromes and nocturnal enuresis (bedwetting). It is believed that TCAs function to increase levels of norepinephrine and serotonin in the brain.

Examples of TCAs include:

  • Elavil (amitriptyline)
  • Tofranil (imipramine)
  • Sinequan (doxepin)
  • Anafranil (clomipramine)

Monoamine Oxidase Inhibitors (MAOIs)

MAOIs are a class of antidepressants believed to increase levels of norepinephrine, serotonin, and dopamine in the brain. They are effective for the treatment of the major depressive disorder, panic disorder, and other anxiety disorders. Because of potentially dangerous interactions with certain foods, beverages, and other drugs, particularly those that influence serotonin, MAOIs are usually not considered as a first-line treatment.

Examples of MAOIs include:

  • Nardil (phenelzine)
  • Parnate (tranylcypromine)
  • Marplan ( isocarboxazid)
  • Emsam (selegiline)

Other Psychiatric Medications

  • BuSpar (buspirone)
  • Eskalith (lithium)
  • Desyrel (trazodone)

Analgesics (Pain Killers)

Antibiotic/Antiretroviral Medications

  • Zyvox (linezolid)
  • Norvir (ritonavir)

Herbal Drugs/Dietary Supplements

  • Hypericum Perforatum (St. John’s Wort)
  • Ginseng/Panax

Street Drugs

  • Amphetamines
  • Cocaine
  • LSD (lysergic acid diethylamide)

This list is not meant to be all-inclusive. To avoid increasing your risk of developing serotonin syndrome, tell your doctor about all drugs and dietary supplements you are taking. If you develop symptoms of serotonin syndrome, seek immediate medical attention.

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