Clinical Overview: Evidence Surrounding the Use of Venlafaxine for Vestibular Migraine

In 2012, migraine was ranked as the seventh highest cause of disability worldwide.¹ A survey conducted in 2020 found that 22% of those suffering from migraine in the United States missed work and 60% worked while impaired, which demonstrates the significant burden migraine can have on a patient's quality of life.²

Furthermore, it is estimated that out of the 11.9% of the general US population who experiences dizziness, nearly 25% of those suffer from vestibular migraine (VM).³ VM patients experience vestibular symptoms, including spontaneous vertigo, head motion intolerance, oscillopsia, directional pulsion, and unsteadiness that can sometimes last for days.^4,5

Because of these debilitating symptoms, psychiatric disorders such as anxiety and depression are often observed as secondary comorbidities.⁶ Migraines are common yet misunderstood, therefore it is important that various treatment options be examined and offered to this patient population.

The purpose of this article is to provide insight into an often underdiagnosed subtype of migraine and the promising evidence surrounding its prevention and treatment with venlafaxine, a commonly used serotonin and norepinephrine reuptake inhibitor. Although no set pattern or combination of symptoms are specific to VM, the diagnostic criteria according to the International Classification of Headache Disorders (ICHD) include 5 or more episodes of vestibular symptoms that can last between 5 minutes and 72 hours plus 1 or more migraine features (headache, sensitivity to sound, sensitivity to light, or visual aura) during at least half of the vestibular episodes, plus a current or previous migraine diagnosis.⁷

In more than 66% of patients who experience VM, the vestibular symptoms are often accompanied by aural symptoms, such as tinnitus, ear pressure or pain, and muffled hearing.⁵ Contrary to what is experienced with traditional migraines, it is not uncommon for VM to be headache-free, leading to it commonly being misdiagnosed or underdiagnosed.⁸

It is essential for clinicians to exercise caution when establishing a diagnosis of VM, as misdiagnosis often occurs due to overlapping symptoms between VM and Meniere disease (MD), another vestibular disorder.⁹ It is estimated that more than 50% of patients with VM received a previous, incorrect diagnosis of MD.

Symptoms commonly observed in both conditions include vertigo, cochlear symptoms, nausea, vomiting, and photo- and phonophobia. Though there are no specific symptoms that aid in differentiating between VM and MD, some symptoms more commonly seen with VM are migraine headache attacks that last from seconds to days, a history of motion sickness, and a family history of migraine (Table 1⁹).

Table 1. Differentiating Symptoms of VM and MD⁹

VM more commonly affects females, whereas MD more commonly affects males. The average age of onset for VM is the early 40s, whereas MD typically presents in the late 40s. Patients with VM are also more likely to experience cognitive symptoms, such as wariness and brain fog.

The inclusion of these cognitive effects could explain the comorbid psychiatric conditions often experienced in someone with VM.⁹ 

There are many studies that show the link between various neurotransmitters including serotonin, norepinephrine, and dopamine, and the role they play in migraines.¹⁰ For this reason, medications typically used to augment mood are also beneficial in preventing and treating symptoms associated with migraines.

Currently no antidepressants are FDA-approved for migraine prevention, but their off-label use for this is widely practiced. It is thought that selective serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants (TCAs) commonly used to prevent migraine work through their interaction with serotonin and norepinephrine receptors.^1,11

Triptans, a drug class frequently used for its abortive effects during acute migraine attacks, work as agonists at 5-HT_1B/1D receptors on intracranial blood vessels and nerves within the trigeminal system causing vessel constriction and inhibition of proinflammatory neuropeptide release.¹³ This constriction/inhibition leads to increased levels of circulating serotonin.

Thus, the justification for using these medications is that in patients with migraines, serotonin levels are chronically low but transiently increase during migraine attacks.¹³ By maintaining more consistent levels of serotonin, these medications may help prevent attacks.

Traditionally, the treatment for VM has been based on evidence obtained from observational studies and expert experience.¹⁴ Prophylactic pharmacotherapy is recommended when VM attacks occur multiple times per month, last for several weeks, or severely impact a patient’s lifestyle.

Medications used as prophylactic treatment include beta blockers, TCAs, SSRIs, topiramate, valproic acid, and flunarizine.⁸ Commonly reported adverse effects that can limit their use include orthostatic hypotension, bradycardia, sedation, appetite suppression, weight gain, depression, and anticholinergic effects, such as dry mouth and urinary retention.¹⁴

A meta-analysis performed by Wang and colleagues sought to review the evidence surrounding venlafaxine against frequently used prophylactic agents (Table 2).¹⁵ Compared to TCAs and SSRIs, venlafaxine showed comparable effects in terms of decreasing migraine duration, intensity, and frequency.

Table 2. Details of Studies Included in Meta-analysis^8,15,17-20

Of the 5 trials analyzed, 2 of them assessed efficacy using the dizziness handicap inventory (DHI) scoring method, which scores patients’ symptoms based on the number of “yes,” “sometimes,” and “no” responses to specific questions. The DHI scoring criteria include functional (restrictions, difficulties, avoidances), emotional (feelings of frustration, anger, embarrassment, etc.), and physical (which activities exacerbate the problem) domains. The criteria that compose this scoring can be found by clicking here.

In trials that compared venlafaxine to propranolol, flunarizine, and valproic acid specifically for VM prevention, they found that there was no significant difference between venlafaxine and the others in terms of decreasing the physical or functional portions of the DHI score, but there was a significant decrease in the emotional domain of the DHI score. This suggests that it could be an appropriate medication to consider in those suffering with VM and comorbid depression.¹⁵ 

As some of the most accessible health care providers, it is important that pharmacists keep VM in mind as a differential diagnosis in their patients experiencing dizziness. It is often mistaken for other vestibular, neurologic, or psychiatric conditions because of the commonly associated comorbid conditions.

There are many medications approved for the prevention and abortion of migraine headache, however, the ideal candidate for these therapies is not always clear. A patient eligible for venlafaxine might be an adult with reliable medication adherence, a previous diagnosis of dizziness, motion sickness, depression or anxiety, and migraine headaches that can sometimes last for days.

Though not completely understood, there is a link between serotonin and migraine. Other antidepressants have proven efficacious in limiting the severity of migraine symptoms; however, of those studied in the setting of VM, only venlafaxine was able to significantly combat the emotional symptoms associated with this condition in addition to easing migraine burden. Because of the effects venlafaxine has on serotonin in the brain, it can be useful for both mood elevation and VM symptom prevention.

About the Author

Emilie Parkman, PharmD candidate 2023, Medical University of South Carolina College.

References

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