Desvenlafaxine (Pristiq): A Potential Off-Label Treatment for Migraine

Desvenlafaxine (Pristiq): A Potential Off-Label Treatment for Migraine

Click for the full list of the 50 uncommon migraine preventives

What is Desvenlafaxine?

Desvenlafaxine is a serotonin-norepinephrine reuptake inhibitor (SNRI). Therefore, it inhibits the reuptake of serotonin and norepinephrine.

Desvenlafaxine is also a metabolite of venlafaxine, another SNRI, which we talked about previously and is also on the list of uncommon migraine preventives. So what is the difference between the two? Desvenlafaxine is more potent than venlafaxine. 

Desvenlafaxine is a prescription medication that is FDA-approved to treatment of major depressive disorder (MDD). It is sometimes used as an off-label migraine preventive as an alternative to venlaxafine. 

How Does Desvenlafaxine Work?

Desvenlafaxine works by inhibiting the reuptake of serotonin and norepinephrine thereby increasing their levels in the brain. Desvenlafaxine has more affinity to the norepinephrine reuptake inhibitor and, thus, allows for an increased concentration of norepinephrine than serotonin. We do not know if this benefits migraine patients yet because there are no studies. 

Desvenlafaxine as a Potential Treatment Option for Migraine

There is currently no research available for desvenlafaxine and migraine prevention, but because it is a potent metabolite of venlafaxine, we assume that the studies for venlafaxine may be applied. 

In one study published in the Journal of Head and Face Pain, venlafaxine was found to be more effective than placebo and safe as a migraine preventive. 


In a randomized, double-blind, crossover study, venlafaxine was found to have similar efficacy and less adverse effects when compared to a common firs-line migraien preventive amitriptyline


Potential Side Effects of Desvenlafaxine

Common side effects of desvenlafaxine include nausea, headache, dry mouth, insomnia, and constipation. If you experience any severe side effects or have concerns about taking this medication, it is important to speak with your healthcare provider.

There is an FDA black box warning against desvenlafaxine as it can increase suicidality, cause depression exacerbation, hypomania/mania, and serotonin/neuroleptic malignant syndrome.

Other Considerations for Desvenlafaxine

Desvenlafaxine comes in a tablet that is 50 mg or 100 mg. It cannot be split so one cannot titrate up or wean off. It is also more expensive than venlafaxine. 

Do not use desvenlafaxine if you have used an MAO inhibitor in the past 14 days.

Risk of serotonin syndrome if used with triptans, but unlikely. Speak to your healthcare provider.

This is a cursory understanding of uncommon migraine medications. This is only to be used as a resource to go to your neurologist with. 

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