Taking Effexor XR (Venlafaxine) With Tramadol

In our latest question and answer, the pharmacist discusses the potential interaction between Effexor XR (venlafaxine) and tramadol.

Dec 28, 2017

Chuck asked

Can you take Effexor XR (venlafaxine) 300mg with tramadol 50mg together?


There is an interaction between Effexor XR (venlafaxine) and tramadol. Caution is advised when combining the two medications and the combination is generally recommended to be avoided. Most sources list the interaction at moderate to major. Below, we discuss the interaction in detail.

Effexor - Tramadol Interaction

Both Effexor (venlafaxine) and tramadol can cause an increase in the neurotransmitter serotonin, increasing the risk of a rare, but serious condition known as serotonin syndrome. Serotonin syndrome is characterized by a variety of symptoms including:

  • Hyperthermia
  • Muscle rigidity/spasm
  • Mental status changes
  • High blood pressure
  • Agitation
  • Confusion

Serotonin syndrome is uncommon, but if it occurs, is a serious medical emergency that needs to be treated immediately. There are many medications on the market that affect serotonin, including some available over the counter (e.g. the cough suppressant dextromethorphan). The more medications you take that can potentially increase serotonin, the greater the risk.

In addition to the information described above, the combination of Effexor and tramadol may have a slightly higher risk of serotonin syndrome than other drug combinations.

Effexor may inhibit a metabolizing enzyme in the body known as CYP2D6. This enzyme is responsible for the metabolism of a large number of medications, including tramadol. Inhibition of this metabolizing enzyme may theoretically increase levels of tramadol in the blood, thus increasing serotonin activity more than usual. 

Effexor Mechanism Of Action

Effexor is classified as an SNRI (Serotonin Norepinephrine Reuptake Inhibitor). It works by increasing the amount of serotonin and norepinephrine available in the brain, two neurotransmitters that are thought to be important in the development of depressive symptoms.

Tramadol Mechanism Of Action

Tramadol has a complex mechanism of action, working in a variety of ways. It is thought to work by stimulating opioid receptors, as well as increasing the neurotransmitters serotonin and norepinephrine. It is thought that serotonin activity is more affected with higher doses.


As both tramadol and Effexor increase levels of serotonin, caution is advised when using both together. If the combination is necessary, it is important for your doctor and pharmacist to know your entire medication list to avoid use of other medications that affect serotonin. In addition, it is good to know what to look out for in regard to serotonin syndrome symptoms, even though it is a rare occurrence. 

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