vertigo treatment: antihistamines better than benzos

 A recent systematic review and meta-analysis found that antihistamines provided greater vertigo relief than benzodiazepines (see vertigo antihistamine better than benzo jamaneurol2022 in dropbox, or doi:10.1001/jamaneurol.2022.1858) 

 

Details:

-- 17 RCTs were identified with a total of 1586 participants

-- diazepam was the major benzodiazepine studied, though lorazepam was used in one study

-- antihistamines used included: betahistidine (2 studies), cinnarizine (4 studies), dimenhydrinate (7 studies, this is OTC generic of dramamine), flunarizine (2 studies), meclizine (1 study), and promethazine (2 studies)

-- antihistamines were compared with benzodiazepines in 3 studies, with placebo or no treatment in 7 studies, and with other active controls in 6 studies (including methylprednisolone, various repositioning maneuvers, and some others)

-- primary outcome: change in 10- or 100-point vertigo or dizziness visual analog scale (VAS) at 2 hours after treatment with either an antihistamine or benzodiazepine (the "2-hr" time-span was from 30 minutes to 4 hours)

-- secondary outcomes: change in nausea VAS at 2 hours, use of rescue medications at 2 hours, and improvement of resolution of vertigo at one week or one month

 

Results:

-- 7 trials with 802 participants evaluated the primary outcome:

    -- single-dose antihistamines resulted in significantly more improvement in the 100-point VAS scores as compared to benzodiazepines, difference 16.1 (7.2-25.0), in 3 trials with a low risk of bias

    -- assessing all 7 studies, antihistamines were not associated with a statistically significant improvement over other comparators, difference 7.4 (-1.1 to 15.8), a strong trend to antihistamine benefit

        -- including 2 additional studies that did not publish standard deviations (and making some assumptions), point-estimate results of the sensitivity analysis (now with 1152 patients) were nearly identical to the primary analysis, with a difference of 7.5 (0.8-9.2), though now statistically significant

-- 2-hour nausea VAS: one study finding antihistamines were superior to benzos, mean difference 5.90 (2.15-9.65), but no difference between antihistamines and non-benzodiazepine active controls

-- need for rescue medications: antihistamines were better than benzodiazepines (1 study): risk ratio 3.00 (1.49-6.02), no difference between antihistamines and non-benzodiazepine controls

-- improvement at one week:

    -- benign positional paroxysmal vertigo, BPPV (3 studies): marginal benefit of antihistamines, risk ratio 1.10 (1.00-1.21)

    -- non-BPPV (3 studies): antihistamines better than placebo or no medication, risk ratio 1.66 (1.06-2.59)

-- resolution at one week: no difference for BPPV or non-BPPV, comparing antihistamines to placebo or no medication

-- either improvement or resolution at one month: neither  outcome showed benefit of antihistamines over control

-- one high-quality small trial (20 patients) did find that benzodiazepines had inferior results to placebo for acute vertigo

-- benzodiazepines did not reduce or improve nystagmus compared to placebo, though antihistamines did

 

-- adverse events: no significant difference between antihistamines versus benzodiazepines, antihistamines versus placebo or no medications, or antihistamines versus non-benzodiazepine active controls

  

Commentary:

-- vertigo is quite common, affecting 20% of adults, with a higher incidence in women and older individuals

-- repositioning techniques (e.g. Epley maneuver) are the preferred treatment for BPPV, the most common vertiginous condition

    -- however, medications are often prescribed, perhaps in the event of recurring symptoms after the repositioning maneuvers, with prescriptions typically for antihistamines and benzodiazepines

-- the study found moderately strong evidence that single-dose antihistamines resulted in greater improvement in vertigo at two hours then single-dose benzodiazepines

 

Limitations:

-- there were a small number of studies included in this meta-analysis, and many of the studies were quite small in number (studies ranged from 18 to 200 patients)

-- there are many causes of vertigo, including BPPV, Ménière’s disease, acoustic neuroma, other central nervous system pathology, drug toxicity, vestibular neuritis, herpes zoster, vestibular migraine, etc.). The study did not provide sufficient granular information of the causes of the vertigo, for which different medications and approaches may be appropriate

    -- there are no individual-level granular data to allow better insight into therapeutic effects of different strategies

        --  overall, there were not enough studies to assess important subgroup analyses, limiting our ability to see patterns of benefit

-- the study was unable to assess differences in dosing of different medications, and it is possible that there was variability in adequate dosing that could affect outcomes

-- there is no established clinically relevant difference in vestibular VAS, as there is with the pain VAS. Is the difference of 16.1 for the primary outcome clinically meaningful??

-- several of the studies had a high risk of bias, which was more likely to favor interventions over controls

 

So, way back in the Stone Age when I was a resident, we were told that benzodiazepines (diazepam in particular) were the strongest inner ear sedatives for those with severe acute vertigo, and meclizine was the drug of choice as the antihistamine. This study seems to have set that on its head:

-- there was no evidence that benzodiazepines were superior to any other treatment, and in fact they were inferior to antihistamines

    -- so, based on this systematic review, there does not seem to be any place for benzodiazepines in treating acute vertigo; and, benzodiazepines do have some significant adverse reactions (respiratory depression) as well as an addictive potential

-- though meclizine is a popular treatment for vertigo in the US, there is no evidence that its efficacy is different from any other antihistamine. though there was no information about some of the commonly used antihistamines now in the US (eg diphenhydramine, or the "nonsedating" ones such as loratadine)

geoff

 

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