Median dose (mg/day)
5.2.4 Review of the Literature
In a retrospective review of 19 patients, Bisdorff evaluated the efficacy of lamotrigine in treating patients with migraine headaches with vertigo. The dose was 100 mg/day and the patients were followed for 3–4 months. At the end of the observational period, the frequency of vertigo attacks was significantly decreased. Vertigo duration and headache frequency were also reduced, although not to a statistically significant extent. This medication was well tolerated in this group of patients .
Other studies evaluating the effect of lamotrigine on migraine aura found it to be quite effective, although no study specifically mentioned vestibular migraine. An animal study evaluating CSD in rats showed that lamotrigine was effective in reducing CSD, while valproate and riboflavin had no effect . Lampl and colleagues conducted an open longitudinal pilot study of lamotrigine on 15 patients who had migraine with aura. Dosing was started at 25 mg a day. The dose was titrated up as needed to a maximum dose of 100 mg/day to control the patient’s symptoms. All patients responded favorably to the medication with a decreased frequency and severity of their aura symptoms . A small case series showed lamotrigine to be effective in basilar migraine with aura, although no specific reference to vestibular symptoms was made . Other studies have shown an overall decrease in aura frequency, with one study showing resolution of a prolonged aura (months to years) after treatment with lamotrigine [11–13].
Although valproate has been well studied for migraine headache prophylaxis, only one study has investigated its effects on VM. Celiker et al. studied the effects of valproic acid on three groups of migraine patients: migraine with vertigo, migraine with dizziness, and migraine without vestibular symptoms. They also compared electronystagmographic findings between the groups, both before and after treatment. Two of the original 43 patients dropped out due to medication side effects. There was a significant decrease in the number of attacks in the migraine with vertigo and the migraine with dizziness group (p < 0.001). There was also a significant decrease in vestibular symptoms in patients whose symptoms were not related to the headache period. ENG findings did not change between the pretreatment and post-treatment conditions .
There have been two studies investigating topiramate as a prophylactic treatment of VM. The first consisted of a group of 10 patients who met the Neuhauser criteria. The average dose patients received was 100 mg/day. One of those patients stopped taking the medication due to side effects. The other 9 patients were without vestibular symptoms at the end of a 9-month period, with only 2 of those patients experiencing an attack over that time frame . The second was an open-label study looking at the effect of topiramate at different doses, 50 and 100 mg/day. Fifteen patients were recruited into both groups. Both efficacy and tolerability were studied. In the low-dose group, 14 of 15 patients had improvement of their vertigo symptoms, with 6 of those having complete relief of their symptoms and only 1 having no change. All patients tolerated this dose well. In the high-dose group, 12 of 15 had improvement in their dizzy symptoms, while 3 had no change. Four patients in this group could not tolerate the high dose and dropped out in the first month of the study. Overall there was no difference between the two dosing groups in regard to vertigo severity and frequency . In a study by Lampl looking at migraine aura and topiramate, the authors found that the drug improved headache symptoms, although did not statistically influence aura frequency or duration .
Similar to other migraine prophylactic medications, levetiracetam (an antiseizure medication) has inhibitory effects on neuronal calcium channels. An open-label trial consisting of 16 patients with migraine with aura were treated with levetiracetam for 6 months at a dose of 1,000 mg/day. The frequency of attacks was significantly reduced over the first month (p < 0.001). Attack frequency was further reduced in the second month (p < 0.001) and again in the third month (p < 0.001). This effect persisted over the next 3 months. Duration of the aura was decreased as well. Six of these patients had minor side effects (dizziness, nervousness, somnolence), but none stopped taking the medication .
There have been a handful of studies that compared various different prophylactic medications within one study. These medications were prescribed according to a specific treatment algorithm or in a nonstandardized fashion according to specific patient characteristics. In a series of 100 patients, Baier et al. reviewed their series of patients treated for VM. Of the 100 patients, 74 were prescribed prophylactic medications for their symptoms. These were delivered in a nonstandardized fashion. The remaining 26 patients were treated with conservative therapy consisting of dietary modifications, lifestyle changes, physical therapy, and progressive muscle relaxation. All patients treated pharmacologically showed a decrease in vertigo duration, intensity, and frequency. The conservative therapy group only showed a decrease in vertigo intensity. Of the patients treated with pharmacologic therapy, five stopped the medications due to side effects (4 beta-blocker, 1 calcium channel blocker) .
Another large series of 89 patients compared outcomes for treatment of VM. Of the 89 patients, 59 (66 %) were treated with dietary changes, 7 % were treated with lifestyle changes, and balance physical therapy is used in 27 %. Prophylactic medications were used in 79 of those 89 patients, and the initial drug of choice was tailored to the specific patient based on the medical history. Benzodiazepines were the most commonly prescribed medication, alone or in combination, at 90 % (clonazepam most often). TCAs were used in 42 % of patients, and beta-blockers were used in 33 % of patients. SSRIs and calcium channel blockers were used, but to a lesser degree. In this series of patients, 44 % of patients only needed a single medication, with 33 % requiring two medications, either alone or in combination. Likewise, 15 % used three medications, with the rest using four or more medications (again, alone or in combination) to achieve symptom control. At the time of symptom control, 67 % required only one medication and 25 % needed two medications, with the rest of the patients requiring three or more medications for symptom control. All 10 patients treated with non-pharmacologic measures were continuing this treatment at follow-up. Out of the 79 patients treated with medications, 60 were still taking their medications. Of the 19 that stopped the medication, 8 stopped due to symptom control, 7 had symptoms under satisfactory control, 3 had significant side effects, and 1 stopped due to lack of control of symptoms. Of the patients with episodic vertigo, 92 % had either a complete response or had significant improvement in their symptoms. This same degree of improvement was achieved in 89 % of patients with positional vertigo and 86 % with non-vertiginous dizziness. Although the majority of patients were treated with medications, outcomes were not reported in regard to medical therapy versus dietary/lifestyle modification or a combination thereof .
Maione reported on his series of 53 patients with VM. Again, medications were chosen in a nonrandomized fashion based on the patient’s characteristics, drug properties, and side effects. The most common medications used were beta-blockers, benzodiazepines, and calcium channel blockers, in that order. Eight patients needed to have their medication changed due to side effects, inefficacy, or a contraindication based on a new diagnosis. Some females underwent estrogenic management as well (2 patients). No mention of dietary or lifestyles changes was made. The outcomes in these patients were as follows: 28 % had complete control of symptoms, 42 % had substantial control, 20 % moderate control, and 11 % had minimal or no control of their symptoms. Of those with recurrent vertigo spells, complete resolution of their spells occurred in 58 %, a >50 % reduction of attacks in 24 %, <50 % reduction of attacks in 15 %, and no reduction in 3 % .
Alternatively, some centers base therapy on a treatment algorithm. In a series of 81 patients, Reploeg and Goebel treated patients in a stepwise fashion. First-line treatment was dietary modification. If symptoms were not controlled on dietary modification alone, patients were started on 10 or 25 mg of nortriptyline and titrated up to 50 mg for symptom control. If this did not result in symptom control, atenolol was prescribed at 25 mg and was titrated up to 50 mg if necessary, usually as monotherapy, but occasionally atenolol was used in addition to nortriptyline. For symptoms that persisted beyond this, a neurology consultation was obtained. Overall, 72 % had complete or greater than 75 % reduction of the frequency of their symptoms. Thirteen of the 81 patients responded to dietary modifications alone. Those who needed nortriptyline along with dietary modifications had an overall 78 % response rate to this treatment. The response rate of diet plus beta-blocker/other drugs (SSRI, CCB, valproic acid, carbamazepine, and gabapentin) was 57 %. Of those prescribed nortriptyline, 3 of 68 could not tolerate the medication due to side effects, with 1 of 19 stopping their beta-blocker for the same reason .
A similar approach was used by Mikulec and colleagues. In patients with VM, a caffeine cessation trial was instituted for the first 4–6 weeks of treatment. They were then assigned to receive nortriptyline or topiramate. Of those patients who did not respond favorably to the medication, some were switched with the other study drug (i.e., nortriptyline nonresponders were prescribed topiramate and vice versa). Five out of the 34 (15 %) patients treated with caffeine restriction alone had some response to reduction in their caffeine intake, although all went on to be treated with medications. The response in patients receiving nortriptyline was 57 %, while the response rate for topiramate as 17 %. Overall success rate for diet modification with or without medications was 75 % .
In 2005, Furman and colleagues proposed a new disorder, migraine-anxiety-related dizziness, or MARD, citing overlap between migraine, anxiety, and balance disorders as well as a high incidence of psychiatric comorbidities in patients with migraine. In this population of patients where vestibular symptoms predominated, prophylactic therapy with an antidepressant (imipramine/sertraline) plus benzodiazepine (clonazepam/diazepam) was recommended. In those patients where anxiety predominated, an SSRI such as paroxetine was recommended; benzodiazepines were used as a supplementary medication for those with significant anxiety and balance symptoms .
Acetazolamide has been shown to be useful in treating familial hemiplegic migraine with essential tremor. Baloh published a series of five patients, all from the same family, who had a reduction in their vertigo spells in addition to decreased severity of migraine headaches and tremor .