Drug Interactions: Antidepressants and Tramadol.

Q: There is a warning associated with antidepressants and its concomitant use with tramadol. Which of the following antidepressant have least risk of this drug interaction with tramadol (compared with other antidepressants)?

 


 

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Tramadol is indicated for the management of moderate to moderately severe pain in adults.

 

Mechanism of action:

  • μ-opioid receptors agonist

  • weak inhibition of re-uptake of norepinephrine and serotonin.

 

Note that tramadol have low binding affinity to μ-opioid receptors, but it’s metabolite (O-desmethyltramadol) have higher binding affinity for μ-opioid receptors. 

 


Two important warnings are mentioned in tramadol’s package insert:

1. SEIZURES

2. SEROTONIN SYNDROME

 

The risk for both conditions increases with co-administration of antidepressants.

 


TRAMADOL’S INTERACTIONS WITH ANTIDEPRESSANTS:

 

SEVERE (CONTRAINDICATION): DO NOT USE TOGETHER.

  1. Monoamine oxidase inhibitors

 

MAJOR: MONITOR PATIENT CLOSELY.

  1. SSRIs

  2. Bupropion

  3. Duloxetine

  4. Venlafaxine

  5. Nefazodone

 

MODERATE (LIMITED EFFECTS):

  1. Mirtazapine

  2. TCAs

  3. Maprotiline

 

CONCLUSION: Tramadol is only contraindicated in combination with MAOIs but not other antidepressants.

 

This above classifcation is from: Psychiatry (Edgmont). 2009 Apr; 6(4): 17–21.

 


ADDITIONAL FACTORS INCREASING THIS RISK:

 

  1. Increased age

  2. Higher dosages

  3. use of concomitant potent cytochrome P450 2D6 inhibitors

 


CYP2D6 INHIBITORS

 

In addition to above information, consider CYP450 status of medications.

Tramadol is 2D6 substrate –> these inhibitors may reduce metabolic clearance of tramadol –> increasing the risk for serious adverse events including seizures and serotonin syndrome.

 

Among antidepressants avoid followings if possible:

  1. Fluoxetine (strong 2D6 inhibitor)

  2. Paroxetine (strong 2D6 inhibitor)

  3. Bupropion (strong 2D6 inhibitor)

  4. Duloxetine (moderate 2D6 inhibitor)

  5. Sertraline (moderate 2D6 inhibitor)

  6. Amitriptyline (according to package insert, but amitriptyline is a 2D6 substrate like tramadol)

 


Source:

  1. Tramadol package insert.
  2. Psychiatry (Edgmont). 2009 Apr; 6(4): 17–21.
  3. The Flockhart Table™, Indiana University.
  4. J Pharm Pract. 2014 Feb;27(1):71-8.

Please do post your questions or comments below. 


Dr. Harvinder Singh, M.D. (Admin)


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