Most Used Vertigo Medications, Their Efficacy and Side Effects

In this disorder, the person has a sensation of movement or spinning that is often described as dizziness.

A discussion of the pharmacological treatment of vertigo should begin with a discussion of the neurotransmitters used to signal in the vestibular system. This discussion is located here.

Entrance Exams

Anticholinergics

Anticholinergics affect compensation, producing reversible overcompensation if administered after compensation for a vestibular imbalance has been achieved (Zee, 1988).

These medications are often available without a prescription. Some examples are meclizine, dimenhydrinate, and diphenhydramine. Most are combined anticholinergics / antihistamines .

The antihistamine component has long-term drowsiness and weight gain side effects.

Unlike the antihistamines that will be discussed later, pure anticholinergics are ineffective if given after symptoms have already appeared.

All of the anticholinergics used to treat vertigo have prominent side effects of dry mouth, dilated pupils, and sedation. Diphenidol (Vontrol), is also an anticholinergic, although little used in the US.

There are also some reports of scopolamine-inducing migraine, as well as a withdrawal syndrome .

Cholinergic agonists that cross to the brain, such as physostigmine, can cause motion sickness syndrome (Soto et al, 2013).

Cholinergic agonists that do not cross the brain, such as neostigmine, do not cause motion sickness.

Addiction is possible for anticholinergics

This has been described for scopolamine (Luetje and Wooten 1996), and other anticholinergics can also have addiction syndromes. Withdrawal has been described using an agent similar to meclizine, diphenhydramine.

Overdose is similar to acute psychosis. Hospitalization can precipitate withdrawal. (Thomas and others, 2009).

Antihistamines

With the possible exception of astemizole (Hismanal) in Meniere’s disease (Turner and Jackson, 1989), antihistamines that do not cross the blood-brain barrier are not used to control vertigo.

Unfortunately, astemizole does not appear to be helpful in general, as it is ineffective in preventing motion sickness (Kohl et al, 1987) and because it has significant potential toxicity.

There is evidence of the participation of several types of histamine receptors, Serafin et al. (1993) where it is reported that histamine increases firing in MVN cells, mediated through the H2 receptor.

H1 receptors are present in the vestibular nucleus of the guinea pig, but do not appear to be relevant for vertigo.

Furthermore, it does not appear that the therapeutic effects of H1 receptor blockers can be attributed to H1 blockade (Timmerman, 1994).

H3 receptor agonists appear to cause the same result as H2 receptor blockade. Most antihistamines also have a calcium channel blocking effect (after Timmerman, 1994).

Hormone agonists that target receptor subtypes are also used to treat vertigo (eg, betahistine).

This can sometimes result in a peculiar situation where people take both antihistamines and histamine agonists at the same time.

In addition, they increase the affinity of the chloride channel opening. There are differential effects between benzodiazepines on Gaba-A receptor subtypes. In small doses, these drugs are extremely helpful.

Lorazepam and klonazepam are particularly useful agents because of their effectiveness and simple kinetics. Addiction, the biggest problem, can generally be avoided by keeping the dose at 0.5 mg BID or less.

Other problems include an increased incidence of car accidents (risk x1.5) and hip fractures (risk x 1.8) (Ray, Griffin and others 1987, Ray, Fought et al., 1992).

The risk of falling increases in the elderly in approximately the same proportions. Similarly, low doses of diazepam (Valium) (2 mg) can be very effective for dizziness.

Clonazepam (Klonopin) is as effective a vestibular suppressant as lorazepam (Ganaca et al, 2002). Long-acting benzodiazepines are not helpful in relieving vertigo.

Antieméticos

Relatively new are the 5HT3 agents (Zofran, Kytril). In theory, these agents might not be ideal for emesis related to vestibular imbalance.

The choice of agent depends mainly on considerations about the route of administration and the profile of side effects, for example:

  • Oral agents are used for mild nausea.
  • Suppositories are commonly used in outpatients who cannot absorb oral agents due to gastric atony or vomiting.
  • Injectables are used in the emergency room or inpatient settings.
  • The new agents are used when all else fails.

When an oral agent is appropriate, this agent is generally the first to be used, as it rarely causes more severe adverse effects than drowsiness.

Phenothiazines, such as prochlorperazine (Compazine) and promethazine (Phenergan), are effective antiemetics, probably due to their dopamine-blocking activity, but they also act at other sites.

The pregnancy category ranges from A (through controlled human studies they have not shown a risk to the fetus) to D.

In category D there is positive evidence of human fetal risk, use only in a life-threatening situation or for a serious disease for which it is a safer drug or cannot be used or are ineffective.

Domperidone (Motilium) is an antiemetic that does not cross the blood-brain barrier and therefore has fewer side effects.

Although droperidol has been used in the past, it is no longer recommended.

There is a possible role for newer antiemetics that are 5-HT3 antagonists (ondansetron, Zofran, granisetron, Kytril) used in the treatment of chemotherapy-associated and post-transplant nausea.

The high cost of these agents currently limits their usefulness in treating vertigo, but they are reasonable agents to treat in situations where the more common agents are ineffective or contraindicated.

These agents do not appear to be helpful in preventing motion sickness (Stott et al, 1989). In theory, these agents may be less effective for vestibular triggered emesis than agents with other pharmacological actions.

Agents used in the treatment of motion sickness whose role is currently uncertain

Antidepressants

All antidepressants increase ataxia, and many cause nausea and hypotension . Therefore, one would think that their role would be limited.

However, the ability of antidepressants to control the psychological consequences of dizziness is often helpful (Horii, Mitani et al., 2004) Horii, A., K. Mitani, et al. (2004).

Some antidepressants such as amitriptyline have strong anticholinergic properties that can be helpful in controlling motion sickness. There are several reports of a positive effect, which lacks an explanation.

Calcium channel blockers are the most promising agents in this group. Flunarizine, however, is also a dopamine blocker, and cinnarizine is an antihistamine.

Some calcium channel blockers, such as verapamil , have quite strong constipating effects, which can be helpful in controlling diarrhea caused by vestibular imbalance.

However, calcium channel blockers often have anticholinergic and / or antihistamine activity.

The relative importance of activity associated with calcium channel blockade for vestibular suppression has not been determined (Rascol et al, 1989).

Another problem is that almost all antihistamines have calcium entry blocking capacity and / or calmodulin blocking properties, making it difficult to determine the mechanism of action (Timmerman, 1994).

According to Soto et al (2013), cinnarizine also blocks pressure-sensitive potassium channels, which may provide you with a separate mechanism for the treatment of dropsy.

Calcium channel blockers may be effective in “vestibular menisci” or “benign recurrent vertigo.”

This is due to the fact that people with this diagnosis have a high prevalence of migraine (Rassekh and Harker, 1992), for which calcium channel blockers can be very effective.

According to Soto et al (2013), the most commonly used calcium channel blockers for vertigo are nimodipine, nitrendipine (long-acting) and verapamil.

Other long-acting dihydropyridines such as amlodipine, felodipine, nicardipine, and nifedipine are rarely used.

The author has found daily verapamil to be helpful in about 1/3 of his classic Meniere patients, improving or suppressing attacks, provided a reasonable dose is taken.

This use of verapamil for vertigo has not been studied or approved in the US However, nimodipine has recently been reported to be effective as a Menieres prophylaxis.

Our experience is that only verapamil is used extensively. Galapentin is also a calcium channel blocker (not a GABA agonist despite the name).

Diuretics Carbonic anhydrase inhibitors such as acetazolamide, topiramate, and combinations such as HCTZ-Triamterine are commonly used to treat Meniere’s disease.

They may also have some efficacy in migraine headaches and episodic ataxia. A potassium channel blocker, 3-4 DAP and its close relative, 4AP, has been reported to be helpful for people with ataxia and decreasing nystagmus.

This drug is sometimes used for fatigue in MS, as well as a rare neuromuscular disorder (Eaton Lambert).

Side effects include headache, perioral fatigue and / or distal paresthesia 30-60 minutes after a dose, difficulty sleeping.

Overdosing can cause seizures. 4-AP is a similar agent that has better absorption from the CNS.

Note that the branded version of 4AP is priced 20 times higher than the composite version of the same chemical.

A sodium channel blocker, phenytoin (Dilantin) has also been reported to be protective against motion sickness (Knox et al, 1994).

Gabapentin (Neurontin), carbamazepine (Tegretol), and oxcarbazepine (Trileptal) are also sometimes used successfully in the treatment of vertigo, although their use has not been extensively studied.

Gabapentin has also been used successfully to suppress certain types of central nystagmus (Stahl et al, 1995).

Since these agents affect GABA, which is important in vertigo, an antivertigo effect is reasonable.

The sodium channel blockers Tegretol and Trileptal are particularly useful in paroxysmal disorders such as microvascular compression syndrome and vestibular nerve neuritis.

They are also used occasionally for tinnitus. Because both serum are low in sodium, they are also sometimes used to treat dropsy.

Recent epilepsy agents have been developed that are glutamate antagonists, but as of this writing, they have not been tested as vertigo treatments.

Another Gaba agonist, Baclofen (Lioresal) has shown promise for reducing vestibular asymmetry.

A trial in humans indicated that it is not useful for accelerating vestibular compensation (de Valc et al, 2009), but nevertheless this agent may have other uses.

GABA would be more likely to slow down compensation. This agent may be suitable for patients with uncompensated vestibular asymmetries.

Dopamine blockers for vertigo

There are a wide variety of dopamine blockers used for emesis. These medications can also treat migraine headaches (as they are often effective anti-migraine medications).

In fact, Flunarizine is the dominant migraine prevention drug used in Europe. All are limited by their propensity to cause movement disorders (such as drug-induced parkinsonism) and others.

From our point of view, these drugs should be the “last resort” for the treatment of chronic vertigo conditions.

Flunarizine is a close relative of cinnarizine. However, these drugs are considered acceptable for acute use.

Histamine agonists

Antihistamines used to treat vertigo are usually centrally acting histamine H1 receptor antagonists.

However, in some parts of the world an H1 + H2 receptor agonist and an H3-H4 Serc antagonist (betahistine) are used.

This is an interesting group that has been ready to move from the category of uncertain roles to the more conventional category for decades.

The main problem is that rigorous studies demonstrating efficacy are generally not available, although less rigorous studies abound.

H1 receptors do not appear to be important at all in vestibular function, and the antivertiginous effects of antihistamines are mediated through non-H1 receptors or other drug effects.

Also, the H1 (and H2) effects are minor. The effects of Serc can occur through H2 agonism or H3 antagonism (Timmerman, 1994).

H3 is an autoreceptor that modulates H1 / H2 and other neurotransmitter systems as well.

Recently, a fourth histamine receptor (H4) has been identified. H4 antagonists are reported to suppress firing of rat primary vestibular neurons (Desmadryl et al, 2012).

Furthermore, according to these authors, betahistine does not have a significant effect on the H4 receptor in conventional doses. This may explain recent suggestions to raise the dose to very high levels (eg Strupp et al, 2008).

In the rat brain stem, betahistine produces a slight excitatory response in MVN neurons and reduces the excitatory effect of histamine (Soto et al, 2013).

Pragmatically, a betahistine dose of 16 mg two to three times / day is generally prescribed, although a greater effect is obtained for doses as high as 48 mg (Strupp, et al., 2008).

The reason for this use is because betahistine increases circulation to the inner ear (Halmagyi, 1992) or affects vestibular function through the activity of H3 or H4 receptors.

It is difficult to see why vasodilation should improve vertigo, as vasodilation / constriction are side effects of many medications that have no effect on vertigo (eg, isorbide).

At this time, since H2 agonism would be stimulating, it seems more likely that Serc acts through the H3 or H4 receptor.

Serc is approved by the FDA in the US, but only if dispensed through compounding pharmacies. It was categorized, in essence, as a harmless substance.

Histamine is sometimes prescribed as sublingual drops or subcutaneous injections. Sublingual or subcutaneous histamine is a placebo, as it breaks down rapidly.

However, in our experience, Serc is moderately effective in suppressing the symptoms of Meniere’s disease, for uncertain reasons.

After the pharmacological discussion above, Serc could be expected to be effective in any peripheral vestibular disorder, not just Meniere’s disease.

Opioids

Opioids often cause constipation, and medications that cause constipation generally reduce dizziness as well.

Droperidol (a dopamine blocker) combined with fentanyl (a potent opiate) has been reported to be effective for acute attacks of Meniere’s disease (Soto et al, 2013).

However these drugs are too dangerous to use for this purpose, and there are much easier ways to stop Meniere’s attacks.

Steroids for vestibular disorders

Corticosteroids such as decadron have been recommended for the treatment of Meniere’s disease and vestibular neuritis, in both cases, in an attempt to reduce the duration of a vertiginous episode.

Data on the efficacy of motion sickness are currently in conflict.

There are many possible mechanisms of effectiveness:

  • The modulation of compensation (Cameron et al, 1999).
  • Reduction of immune responses in the inner ear.
  • Reduction of vestibular nerve swelling (Strupp et al, 2004).
  • The reduction of emesis (Wattwil et al, 2003).
  • Increased activity that promotes better recovery through a general effect on the feeling of well-being.

Steroids are commonly used to treat acute attacks of Meniere’s disease.

Occasionally a few days of decadron (4 mg qd) or a medrol dose packet will be used, when faced with severe and incessant vertigo attributed to Menieres disease.

Steroids are used routinely in acute vestibular neuritis, when there is no coincidental serious medical disorder (such as diabetes).

All steroids fall into pregnancy category C, but are generally considered safe during the third trimester.

Sympathomimetics

These drugs increase norepinephrine. Sympathomimetics can increase alertness and counteract the sedative effects of vestibular suppressants.

However, if used for this purpose, combining a vestibular suppressant with a drug aimed at increasing compensation seems somewhat illogical.

Amphetamines are rarely used due to their potential for addiction. Sympathomimetics are generally from pregnancy category C.

Dopamine agonists slow the firing rate in frog hair cells and also reduce the response to glutamine (the excitatory transmitter) (Soto et al, 2013).

On the other hand, dopamine antagonists are rarely used to treat vertigo (eg, Droperidol, phenothiazines), suggesting that the net effect is contrary to the use of dopamine agonists.

Acetyl-leucine

This medicine is marketed and widely used in France. It is claimed to exert a rapid antivertiginous effect when administered intravenously in humans and also to act as a vestibular suppressant.

It is not used in the United States for vertigo. The evidence of its operation is not the best.

Ginkgo Biloba

This extract is widely used in France, but its efficacy is in question (Rascol et al, 1995). It has been reported to suppress vertigo and improve vestibular compensation in animals.

Selective ACH antagonists

The ACH receptor has numerous subtypes, and it seems reasonable that a selective M2 receptor antagonist could cause vestibular suppression without many of the unfavorable side effects of anti-ACH agents.

Unfortunately, little research has been done in this regard today.

Alternative Medicine Agents

The use of the code is recommended for temporary relief of lightheadedness. Para-HEEL and Vertigo-HEEL is also suggested for vertigo.

Several individual agents, it is better to avoid them.

Vareniclina (Chantix)

Recently, this drug, approved by the FDA for smoking cessation, was reported to be helpful in treating cerebellar ataxia (Zesiewicz et al, 2009).

It is extremely surprising to find an agent that improves disorders caused by genetic damage to neurons.

It is also disturbing that the number of individuals in the trial (7) was exactly the same as the number of authors in the study.

In other words, it seems to us that if this drug were effective, the number of subjects should be higher since patients with cerebellar disorders are common.

Timetazidina

This medicine is developed for angina (heart disorder). It has been reported to be useful in a variety of disorders (Soto et al, 2013), including Meniere’s disease.

The evidence for this drug work is currently weak. For example, it is reported to be “as effective” as betahistine.

Trimetazidine can also induce a large number of CNS disorders, largely similar to those produced by dopamine antigonists (ie, similar to haloperidol-Haldol).

Glutamate medications

Memantina

This drug is primarily a glutamate (NMDA) blocker and can be a vestibular suppressant.

It was approved in the United States for the prevention of the progression of Alzheimer’s disease. It is also reported to act on 5HT3, D2, and various cholinergic receptors (Soto et al, 2013).

A similar drug is carvudine, which is a glutamate receptor antagonist.

AMPA

Hallucinogenic NMDA drugs (antagonists)

These include MK-01, phencyclidine (PCP, “angel dust”), and ketamine (“special K”), among others.

Of course, side effects and abuse are a problem. Ketamine produces a general ‘receptive lack of awareness’ as well as dizziness (Soto et al, 2013).