Duloxetine (Cymbalta): A Potential Off-Label Treatment for Migraine

Duloxetine (Cymbalta): A Potential Off-Label Treatment for Migraine

Click for the full list of the 50 uncommon migraine preventives

What is Duloxetine?

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

SNRIs mechanism of action | Download Scientific Diagram

As you can see in this picture, blocking the reuptake (termed reabsorption in the picture) of serotonin and norepinephrine will increase their concentration in the synapses and, therefore, the brain. 

Duloxetine is a prescription medication that is FDA-approved for the treatment of major depressive disorder (MDD), generalized anxiety disorder (GAD), diabetic peripheral neuropathic pain (DPNP), fibromyalgia (FM), and chronic musculoskeletal pain. It is also sometimes used off-label for migraine prevention. Many of the aforementioned conditions are also comorbid conditions of migraine and hence why this medication may be more appealing for those patients. 

How Does Duloxetine Work?

As we stated earlier, duloxetine works by inhibiting the reuptake of serotonin and norepinephrine thereby increasing their levels in the brain. It is important to note that SNRIs are more effective than SSRIs for migraine prevention although they are both used off-label. 

Duloxetine as a Potential Treatment Option for Migraine

There are no randomized controlled trials for duloxetine, but smaller studies are available. 

In one study, there was efficacy of duloxetine in patients with coexisting depression and medication overuse due to chronic migraine. 


In another study, it was found that migraine prophylactic treatment with high-dose duloxetine may be effective in a nondepressed individual.  


Potential Side Effects of Duloxetine

Common side effects of duloxetine 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 duloxetine as it carries an ncreased risk of suicidal thinking and behavior in children, adolescents, and young adults taking antidepressants for major depressive disorder (MDD) and other psychiatric disorders. Duloxetine is not approved for use in pediatric patients

Other Considerations for Duloxetine

Duloxetine is generally prescribed to those patients that cannot be prescribed venlafaxine. 

It is important to talk to your neurologist when planning on stopping this medication. 

Do not use duloxetine 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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