Does Dextromethorphan interact with venlafaxine? (yes)

In this article, we will discuss whether you can take dextromethorphan with venlafaxine or not. This article also discusses the potential side effects of concomitant use of both drugs.

Does Dextromethorphan interact with venlafaxine?

Yes, dextromethorphan and venlafaxine can interact when given together. The clinical data suggests that concomitant administration of dextromethorphan with venlafaxine can lead to side effects. Always consult your healthcare provider before taking these two medications together.

Venlafaxine increases the effect of dextromethorphan by altering its metabolism through the CYP2D6 enzyme. As both drugs inhibit the reuptake of serotonin, the coadministration of venlafaxine and dextromethorphan can increase the occurrence of serotonin syndrome. 

Excessive serotonin causes serotonin toxicity or syndrome, the severity of which is detrimental to the amount of excess serotonin. The three primary features are: 

  • Autonomic hyperactivity
  • Neuromuscular hyperactivity, and
  • Altered mental state (1).

How does dexamethorphan interact with venlafaxine?

Opioids like dexamethorphan have an analgesic effect that is mediated by the mu, delta, and kappa opioid receptors. Nonetheless, numerous opioids also act on different targets, such as inhibiting N-methyl-aspartate (NMDA) receptors and the reuptake of noradrenaline and serotonin. These effects happen in the peripheral and central nervous system, and they could be advantageous or detrimental (2).

The serotonin transporter is a crucial component of the numerous processes that tightly regulate serotonin in the neuronal synapse. A subset of opioids inhibits the serotonin transporter, increasing synaptic cleft serotonin concentration and consequently postsynaptic serotonin signalling (3).

How does dextromethorphan with venlafaxine cause serotonin syndrome?

Venlafaxine is a selective serotonin and norepinephrine reuptake inhibitor. Through the specific inhibition of the 5-HT transporter, they prevent serotonin from being reabsorbed at brain synapses. It functions by restoring the brain’s neurotransmitter equilibrium, which has an impact on emotions and mood. 

Even at therapeutic doses, serotonergic opioids often cause serotonin syndrome when taken with other serotogenic medication, such as venlafaxine. Both drugs have the potential to increase the concentration of serotonin, which might lead to serotonin syndrome.

Additionally, dextromethorphan may increase the chances of experiencing side effects related to antidepressants. For instance, using cold medicines while taking antidepressants may make your headache worsen or increase nausea.

What are the side effects caused by concomitant administration?

Combining dextromethorphan with venlafaxine may raise your risk of developing serotonin syndrome, a rare but dangerous condition that can cause

  • confusion,
  • hallucination,
  • seizures,
  • severe blood pressure fluctuations,
  • excessive perspiration,
  • elevated heart rate, fever,
  • trembling,
  • blurred vision,
  • spasms and stiffness,
  • incoordination,
  • nausea, vomiting,
  • cramping, and
  • diarrhoea.

Serious instances may cause coma or even death.

When to consult the physician?

It is generally considered acceptable to use antidepressants along with cold medications. However, when used with SNRIs, dextromethorphan-containing clod/flu drugs may raise the risk of an uncommon side effect known as serotonin syndrome.

Not only should the patient disclose other prescription medicines, but also report any vitamins and herbal medicines as well. When using venlafaxine, do not exceed the recommended dose. Stay away from mentally demanding activities like driving, cycling, and operating heavy machinery.

For patients and their caregivers, pharmacists should be the main source of pharmacological knowledge about the possible drug interactions between dexamethorphan and venlafaxine. Additionally, pharmacists can help prescribers by offering advice on proper off-label drug use.

It could be advisable to take a few days off from venlafaxine if the patient becomes ill while taking them with cold and flu. Take a sick day, get some exercise, eat healthfully, and drink plenty of water.

Planned or unplanned co-administration of dextromethorphan with venlafaxine is not uncommon. Consult the physician before taking dextromethorphan and venlafaxine together. Regular evaluation of the danger of serotonin syndrome is necessary.

Make sure your doctor is aware of any allergies or medical issues especially if the patient is pregnant or breast-feeding. These factors might influence how you ought to take the prescribed drugs.

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Isbister GK, Buckley NA, Whyte IM. Serotonin toxicity: a practical approach to diagnosis and treatment. Medical Journal of Australia. 2007 Sep;187(6):361-5.


Volpi-Abadie J, Kaye AM, Kaye AD. Serotonin syndrome. Ochsner Journal. 2013 Dec 21;13(4):533-40.


Rickli A, Liakoni E, Hoener MC, Liechti ME. Opioid‐induced inhibition of the human 5‐HT and noradrenaline transporters in vitro: link to clinical reports of serotonin syndrome. British journal of pharmacology. 2018 Feb;175(3):532-43.

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