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Calcium Channel Blockers for Vertigo

Timothy C. Hain, MD

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There is some evidence that calcium channel blockers may be useful in the treatment of vertigo, but these medications are not commonly used for this purpose in the US. Here we attempt to review the mainly European literature, which is more favorable (e.g. Olesen, 1988) in an even handed fashion, hoping to establish a reasonable approach to the use of these agents. At this writing, while there are many reports that these drugs are helpful, it is presently not entirely clear why they are helpful (i.e. whether it is the calcium channel blocking effect or some other effect), as well as in which group of patients they might be helpful.

A positive interpretation of these studies is that the vestibular system, either peripherally or centrally, uses calcium channels, and that these drugs block them, causing vestibular suppression effects.

There is good evidence for calcium channels peripherally, which are predominantly the L-type (Fuchs et al., 1990; Zidanic & Fuchs, 1995). In the periphery, Perin and others reported that in frog, all calcium channel blockers tested reduce resting rate and that L-channel blockers, such as nimodipine, nifedipine, and perhaps verapamil, reduce mechanically evoked activity (2000). Reducing the resting rate might reduce spontaneous nystagmus and reducing mechanically evoked activity might correlate with reduction in movement-induced symptoms. They suggested that L-type channels were involved in hair cell synaptic transmission and that another receptor was also involved with modulating afferent firing (2000).

Centrally, Serafin et al (1990, 1991) have demonstrated the existence of high-threshold (L or N type) and low-threshold (T-type) calcium channels in the vestibular nucleus. 

Davidoff discussed two hypotheses why calcium-channel blockers might prevent migraine (2002). The first hypothesis is that there are actions on neurons, and furthermore that the agents enter the brain (to affect the neurons). This likely varies according to the agent. The second theory is that calcium-channel blockers block vasoconstriction through their effects on smooth muscle. There are major problems with this theory, according to Davidoff.

A negative interpretation is that these are sloppy drugs, and their vestibular suppressant effects are related to slop -- antihistamine or anticholinergic activity, or perhaps just sedation. In support of the idea that the calcium channel effect is not important, Sansom et al (1993) reported that L-type calcium channels do not contribute to static vestibular function in the guinea pig vestibular nucleus (Sansom et al, 1993). However, if L-type blockers affect the periphery as Perin et al reported (2000), the lack of effect on the vestibular nucleus only means that these drugs do not act there.

A third possibility is that some of these drugs are good anti-migraine agents, and they work when migraine is mixed in with Menieres. The reality is probably a mixture of all three.

Calcium channel blockers also have numerous other effects beyond their effects on dizziness. They are generally negative inotrophic agents, which means that they decrease how strongly the heart pumps. Some of them are anti-apoptotic -- in other words, the reduce programmed cell death. The flip side of this is they may slightly increase cancer. In the Syst-Euro trial, nitrendipine (a long-acting dihydropyridine) was found both cardioprotective as well as reduced the prevalence of dementia by 50%. The 50% figure is difficult to believe.

Nimodipine also has been reported to improve learning in aged rabbits (Kowalska and Disterhoft 1994). Verapamil is protective in an animal model against kanamycin ototoxicity (Zhuravskii et al. 2002)

Other long-acting dihyropyridines in the US are amlodipine, felodipine, nicardipine, and long-acting nifedipine.

Amlodipine (Norvasc).

Amlodipine is an inexpensive and commonly used calcium channel blocker, generally prescribed to treat hypertension. There is weak evidence that it is helpful for migraine (Davidoff, 2002).

Cinnarizine (not available in USA)

Diltiazem (Cardizem).

According to Davidoff (2002, page 409), diltiazem has been found helpful in small pilot studies, for migraine. We have not found diltiazem helpful, and in fact, we usually suggest that patients replace it with verapamil when attempting to treat migraine.

Flunarizine (Sibelium, not available in USA)

Lee et al (86) reported that Flunarizine is a vestibular suppressant. The main effects of flunarizine seem likely to be more due to dopamine blocking than calcium channel blocking. Flunarizine is not FDA approved in the USA, in part, due to it's tendency to induce parkinsonism.

Gabapentin (Neurontin)

This poorly named drug which looks somewhat biochemically like GABA, does not interact with the GABA receptor, but rather has a high binding affinity for the Ca(2+)-channel subunit alpha(2)delta, and is a calcium channel blocker.  We don't find gabapentin to be especially useful for dizziness, but it can sometimes suppress nystagmus, even of the congenital variety.

Nifedipine (Procardia)

Nifedipine is a vasodilating calcium channel blocker that has more side effects than most other calcium channel blockers. There is no reasonable rationale for its use in migraine (Davidoff, 2002). We don't find nifedipine useful for dizziness either.

Nimodipine (Nimotop)

Nimodipine is an expensive calcium channel blocker, marketed largely for treatment of subarachnoid bleeding. It has been used for Menieres disease(Lassen et al, 1996), as well as peripheral vertigo (Pianese et al, 2002) with positive results. It is not effective in migraine (Davidoff, 2002). Nimodipine clearly enters the brain to a greater extent than many other calcium channel blockers. If this were an important feature, one would expect that nimodipine would be the most effective of these agents. As this is not true, it seems likely direct effect of calcium channel blockers on neurons is an unlikely mechanism for positive effects of the other agents.

Oddly, nimodipine appears to help learning in elderly rabbits (see below).

The bottom line is that we see no reason to prescribe this drug instead of the cheaper verapamil (see below).

Verapamil (Available) --

See the link above.


References:

Copyright December 18, 2016 , Timothy C. Hain, M.D. All rights reserved. Last saved on December 18, 2016