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Cinnarizine (Stugeron) for Vertigo and Motion Sickness

Timothy C. Hain, MD

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Cinnarizine (not available in USA)

Cinnarizine, not available in the US or Canada, is mainly marketed elsewhere as a H1 antihistamine. It, like betahistine, was originally developed by Janssen Pharmaceutica. Cinnarizine also antagonizes noradrenaline, nicotine and angiotension, and as well it is a calcium channel and dopamine blocker. Some authors also report that it is antisertonergic and antidopaminergic too (Turner et al, 2006). This is not a "rifle drug" ! There is excellent evidence for its dopamine blocking effect. Because Cinnarizine has so many actions, it is difficult to know if positive affects can be attributed to calcium channel blocking vs. actions at other receptors. At this writing (2014), it seems likely that calcium channel blocking has little or nothing to do with its actions on dizziness.

Recent literature suggests that cinnarizine has a special effect in increased inner ear pressure. Haasler (2009) suggested that cinnarizine works in situations where there is “elevated hydrostatic pressure”. This general idea was also put forward by Duwel (Duwel et al., 2005). We have no data on this however.

We think that the quality of large quantity of literature regarding Cinnarizine is rather low.

Dosing:

The usual dose is 12.5 mg three times daily. Of course, 15 mg three times a day is similar. From cinnarizine's side effect profile, it would seem imprudent to take this medication on a chronic basis (see following).

Cinnarizine is also commonly dosed in Europe as a combination product branded Arlevert, containing 20 mg of Cinnarizine and 40 mg of Dimenhydrinate. Dimenhydrinate (also termed Dramamine, Gravol) is a combination of two other drugs -- diphenydramine and 8-chlorotheophylline. The 8-chlorotheophylline is similar to the active ingrediant in tea -- theophylline, and is used in an attempt to decrease the drowsiness caused by the diphenhydramine. Diphenhydramine is an antihistamine branded as "Benadryl" in the US. Thus Arlevert contains Cinnarizine, an antihistamine, and a mild stimulant.

Side effects:

Drowsiness is the main problem with cinnarizine (presumably from antihistamine).

Like its close but stronger relative, Flunarizine, cinnarizine can cause both depression and parkinsonism (Fabiani, Pastro, & Froehner, 2004; Tieve et al, 2004). Flunarizine is routinely used to treat migraine in Europe.

Selected literature:

Pianese et al (2002) found Cinnarizine very effective for peripheral vertigo.

Bartual et al (1989) reported cinnarizine plus dihydroergocristine effective in 90% of 122 patients with vertigo of cervical origin. As the criteria for the diagnosis of cervical vertigo are presently very unclear, the meaning of this observation is uncertain.

Doweck et al (1994) found that cinnarizine reduces VOR gain (roughly by 10%) on rotatory testing.

Scholtz et al. (2004) reported very good results with a mixture of cinnarizine and dimenhydrinate in treatment of acute severe vertigo. They used Arlevert, which as mentioned above, is a mixture of cinnarizine 20 mg and an antihistamine/anticholinergic/stimulant (dimenhydrinate - 40 mg). Dimenhydrinate is actually the combination of diphenhydramine and 8-chlorotheophylline - a mild stimulant similar to caffeine.  Dimenhydrinate is often used as an over the counter antiemetic, and it is marketed under the brand names dramamine, gravol and others. However, although blinded, no placebo arm was included in this study, and perhaps these individuals would have improved anyway. 

There are many other studies of Arlevert, generally all published with assistance from the manufacturer of Arlevert, with similar results. For example, Pytel, J., G. Nagy, et al. (2007). Performed a similar study of 239 patients that was blinded, and placebo controlled. They found that the 20/40 combination as reported above was more effective than placebo as well as 50 mg of cinnarizine. Hahn et al (2008), reported similar results as did Cireck et al (2005), Novotny et al (2012), Scholtz et al (2012), and Pytel et al (2007). Schremmer et al (1999) reviewed 5 randomized trials and concluded that was generally effective.

Other actions attributed to Cinnarizine

There are some papers that suggest cinnarizine increases cerebral blood flow(Gan'shina & Mirzoian, 1996) and some that it is “anti-hypoxic”. (Nikolov, Nikolova, & Milanova, 1984) We are dubious.

Barrett (Barrett, Wright, Taylor, & Proakis, 1988) reported no renal or cardiac effects (this is good). On the other hand, Fabemi (Fagbemi, Kane, McDonald, Parratt, & Rothaul, 1984) suggested that it protected from arrhythmia. We are dubious.

Brage reported no effects on gastic acid (Brage et al., 1986)

As it is very clear that Cinnarizine is a dopamine blocker, as are many antipsychotics, it is reasonable that there may be some therapeutic effects from the dopamine blocking action too. Dopamine blockers are often good at blocking vomiting, and may also have some utility in migraine.

Summary

Overall, there is substantial evidence that Cinnarizine is a vestibular suppressant. As it is a "shotgun" drug, it is not at all clear why it helps, and in particular whether the calcium channel effect is important compared to its multiple other actions, or whether it is superior to other medications such as meclizine. Our guess is that it is somewhat superior, as it combines dopamine blocking and anticholinergic activity with a mild stimulant resembling tea.

We would like to see a study of a "pure" calcium channel blocker combined with other drugs that affect neurotransmitters in a similar way.

Cinnarizine's main problem is that it, like its close relative flunarizine, cinnarizine is a dopamine blocker. Dopamine blockers can cause Parkinsonism. Still, in medicine, other mild dopamine blockers are used routinely, and this is not necessarily a reason to avoid cinnarizine.

 

Sources:

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