The benzodiazepines (BZD) are a family of sedating medications used mainly for treatment of anxiety but they also have use in treating vertigo. For those of us old enough to remember, these drugs (such as valium) were referred to in popular culture as "mother's little helper".
The main purpose of this page is to review current evidence regarding the effects of benzodiazepines on vestibular function. The bottom line is that there is little experimental data, and that current dogma (not well substantiated) is that benzodiazepines suppress vestibular responses and also suppress compensation.
Before beginning, lets acknowledge that benzodiazepines are addictive substances, and are a source of considerable passion regarding their utility for many purposes. When papers are written about "inappropriate use", this means someone has made a moral judgement. Hm. It is important to realize that in situations like this, like politics, there can be many different opinions. Much of this page involves opinions of the author, Dr. Hain, who is a clinician who treats dizziness. We have summarized the literature about addiction at the bottom of this page.
In 2018, 12.6% of the US population received benzodiazepines (BZD), with a 2:1 female:male ratio. Similarly 15% of Europeans received BZD in 2020 (Torres-Bondia, 2020) , and the rate of BZD prescription increases linearly with age (presumably due to insomnia).
Commonly prescribed BZD include diazepam (Valium), lorazepam (Ativan), clonazepam, alprazolam (Xanax) and many others. These drugs are largely used to treat anxiety and insomnia, but also are used to induce sleep, and a variety of other purposes largely involving suppression of the nervous system. They generally are not toxic, in the sense that they generally do not damage organ systems, but also generally are associated with addiction and tolerance.
BZD are GABA modulators, acting to suppress vestibular responses. They increase the affinity of chloride channel opening (Soto et al, 2013). There are differential effects across BZD on Gaba-A receptor subtypes. In small doses, these drugs are extremely useful. Addiction, impaired memory, increased risk of falling, and possibly impaired vestibular compensation are their main shortcomings.
GABA-A receptor drugs increase neuronal inhibition. Other Gaba-A stimulants are alcohol, "Z" drugs -- zolpidem, zopiclone, zaplon -- and barbiturates. Gaba-B receptors are associated with maintenance of a slow inhibitory tone.
Lorazepam and clonazepam are a particularly useful agents when treating dizziness because of their effectiveness and simple kinetics. Addiction, the biggest problem, can usually be avoided by keeping the dose to 0.5 mg/day or less (see discussion below). Other problems include higher incidence of car accidents (risk x1.5), and hip fractures (risk x 1.8) (Ray, Griffin et al. 1987; Ray, Fought et al. 1992). Fall risk is increased in the elderly by roughly the same proportions.
Nevertheless, low doses of diazepam (Valium) (2 mg) can be quite effective for dizziness. Clonazepam (Klonopin), is as effective a vestibular suppressant as lorazepam (Ganaca et al, 2002). Use of alprazolam (Xanax) for vestibular suppression is best avoided because of the potential for a difficult withdrawal syndrome. This is also sometimes seen with clonazepam. Very long acting BZD are not helpful for relief of vertigo. Shorter duration agents, such as lorazepam, are probably safer than the longer duration drugs (such as clonazepam) simply because there is less drug in the body considered over 24 hours.
BZD are commonly used in emergency departments and medical offices to treat vertigo. We think this is reasonable, albeit in small doses. By small, we mean 5 mg of diazepam (usually less), or 1 mg of lorazepam (usually just 0.5 mg). We do not think that this amount of diazepam or lorazepam should be continued for long periods of time, for acute vertigo. However, if all else fails and given objective evidence for vertigo (e.g. nystagmus), we do think that chronic use is justifiable, based on a "less harm" reasoning.
Marill et al (2000) reported that "CONCLUSION: Our results suggest that dimenhydrinate was more effective in relieving vertigo and less sedating than lorazepam at the intravenous doses administered in this study." They used lorazepam 2 mg, and compared dimenhydrinate 50 mg. We think that these authors simply used too much lorazepam (see above).
Hunter et al (2022) compared BZD to antihistamines for patients with acute vertigo. They wrote "Moderately strong evidence suggests that single-dose antihistamines provide greater vertigo relief at 2 hours than single-dose BZD." This study was a "meta-analysis" of other studies. They did not consider the diagnosis. It is generally felt that it is not the antihistamine effect but the anticholinergic that is the main mechanism of action, and we wonder how this review was structured. Antihistamines that don't get into the brain do nothing for dizziness. We don't agree with this paper's conclusion. As mentioned above, there is considerable passion pro and con about BZD -- similar to politics these days. It certainly doesn't match the common pattern of use of these medications in emergency settings.
We think a more nuanced approach would be helpful -- we think that BZD and anticholinergics are both not generally appropriate for the most common type of dizziness (BPPV). We think that both work for Meniere's disease quite well. We are dubious that either is appropriate for more than a few days for vestibular neuritis. So it depends.
Overall, BZD are commonly used to treat dizziness. In our opinion, they are best used in small doses, and ideally for a limited time (e.g. a month). Some patients require small amounts on a daily basis to suppress dizziness. Here it is important to avoid addiction by keeping the prescriptions low dose (see table above).
There are many interesting things to consider concerning how these drugs are handled in the body. In particular, how strong are they (we will call this activity), how long do they last in the blood, how long does their effect last in the brain, and how does this all change as people develop tolerance.
In persons or animals that have never experienced these drugs, the following table illustrates roughly how powerful these are:
Table 1 -- Activity and Time constant of common BZD Drug Lowest effective dose Time constant in the blood "Low dose" to manage chronic vertigo Lorazepam 0.5 12-18 hours. 0.5 mg day Clonazepam 0.5 30 hours 0.5 mg once/day Diazepam 2 mg several, up to 24 hours. 2 mg twice/day Alprazolam 0.25 mg 8 hours (6-12-15) Not recommended Chlordiazepate 7.5 mg 10-30 hours Not recommended
These values all change in people who are tolerant both because the drug may be eliminated more rapidly as well as because the nervous system may develop resistance to the effects of these medications. The "activity" and timing also varies between sleepiness (i.e. sedation) and "dizziness". The "low dose" values above are the amounts that often control chronic dizziness, and also can generally be stopped abruptly without serious consequence (such as seizure) but nevertheless there will almost always be withdrawal effects such as anxiety/panic/sleep disturbance. In people older than 65, we suggest an attempt to reduce benzodiazepine prescriptions, as older people are more sensitive to these medications as well as have other sources of impaired judgement and balance that make these drugs more dangerous. While desirable, this may be a bit of an uphill battle -- there are usually reasons that people take these drugs, perhaps insomnia, that don't just go away.
Some individuals are "habituated" to BZD, and take far more than the doses above. Our thought is that these persons should be "tapered down" on BZD, aiming for the safer "low dose" values. The taper typically takes place over many months -- see additional comments towards the bottom of this page. We think that it is important to use prescription monitoring databases in this situation, and make it clear to patients that only a single medical provider will be controlling all benzodiazepine prescription. A contract is helpful. This is to prevent patients from "gaming" medical providers.
It is our opinion (with partial confirmation in the literature) that BZD decrease vestibular gain and also decrease phase. This results in a total response (gain * time constant) that can be normal, but with a relatively long time constant and lower gain. Although this is our general opinion, reinforced by considerable clinical experience, experimental evidence for the effect on the time constant is not strong.
Morrow and Young (2007) observed that large doses of BZD can reduce the gain of the VOR, almost eliminating it in large doses. This is also the author's opinion.
Barmack and Pettorossi stated that diazepam suppressed the activity of "secondary vestibular neurons", lasting 15-60 minutes (1980). We think that this statement is equivalent to saying that diazepam reduces VOR gain, which is certainly true. They also reported that a dose of 1/2mg/kg (in rabbits) reduced the HVOR gain by 50% (Barmack and Pettorossi, 1980b). The equivalent dose in humans would be 35 mg -- this is far more than nearly any human can tolerate without going to sleep. Of course, rabbits are not people, but again we would agree that diazepam, even in relatively small doses, reduces the gain of the VOR. Our impression, based on experience with patients, is that diazepam also increases the time-constant (i.e. reduces phase lead). Pettorossi et al (1982) suggested that diazepam enhances cerebellar inhibition of vestibular neurons, based on animal experiments. Perhaps this is the mechanism for the effects on gain and phase, suggested above.
Blau et al (2005) reported that there were no effects of 10 mg/day of diazepam administered for 14 days on the rotatory chair test. They reported "CONCLUSIONS: Clinically, the DZ subjects' scores remained within the normal ranges for vestibulo-ocular phase and gain, suggesting that patients in whom drug cessation is problematic may not have to discontinue DZ before testing with the SHA rotational system. ". We disagree entirely with this report from many experiences with patients on BZD. It may be that the "normal ranges" were too wide for these investigators.
Blair and Gavin (1979) investigated the effects of intravenous diazepam on the VOR of monkeys, and reported a decrease in gain and increase in time constant. The time constant is related to phase (see above). This fits with our clinical observations.
Overall, there is remarkably little data on the effect of BZD on VOR gain and phase. It seems certain that BZD suppresses vestibular gain, and we also think it is highly likely that it increases the time constant and increases phase lag (e.g. reduces phase lead). Someone should do a study.
Dogma states that BZD impair vestibular compensation. There are several variants of compensation -- static and dynamic. Static compensation has to do with restoration of tone. This happens, generally speaking, irrespective of the drug environment.
Martin et al (1996) reported that "These results suggest that even high doses of diazepam before and following UL do not result in an impairment of compensation of SN in guinea pig." It is our impression that SN (spontaneous nystagmus) compensates irregardless of medication, and we think this is a reasonable supposition.
Peppard (1986) suggested that amphetamines improved compensation, but that "other drugs" had either little effect on recovery or hindered it.
Ishikawa and Igarashi found no major effect on balance or nystagmus in monkeys given diazepam (1984). We find this peculiar.
Diazepam did not delay vestibular compensation in the cat (Bernstein et al, 1972).
Overall, no substantial data appears to be present to substantiate the dogma that there is an adverse effect of BZD on compensation of vestibular responses.
BZDs are classified as schedule IV drugs by the DEA (ie, "low potential for abuse and a low risk of dependence"). To us, this label seems inappropriate as we think these drugs have a high risk for dependence. On the other hand, it does put the responsibility for managing these drugs mainly into the realm of the primary care doctors, who should know their patients well enough to make judgements.
Addiction to BZD, as well as diversion of prescriptions for use as "street" drugs, is an immense problem. This subject seems to attract passionate appeals against their use, presumably being driven by emotionally trying experiences with dependent persons. BZD, like ethanol containing beverages, are sometimes used to self-medicate anxiety, and for recreational purposes. BZD are rarely sources of death from overdose, by themselves. Nevertheless, when mixed with other drugs, such as alcohol or opiates, BZD can be associated with death due to respiratory arrest. Thus prescription of BZD to persons prone to take "mind altering" substances, such as opiates, is particularly dangerous. BZDs increase the likelihood of respiratory suppression when combined with opiates; It may be that use of BZD impairs the addict's "common sense" and makes it more likely that there will be a drug overdose of alcohol or opiates.
Practically, all BZD are addictive in the sense that they are associated with a withdrawal syndrome after prolonged use. This is of course also true for alcohol and opiates. Addiction is not necessarily a reason to avoid using a useful drug -- but it is part of the "cost benefit" equation. It has been our experience that intelligent, high functioning individuals (such as most attorneys or doctors), almost never take BZD. Hmm.
The decision as to whether or not members of society should be allowed to ingest substances (such as beer, BZD, opiates or marijuana) that alter their judgement, is a legal one, and involves setting the "needle" selecting the amount to which society should be able to control their member's behavior. Of course, this varies from country to country.
From a medical perspective, in the author's opinion, BZD are very effective drugs to control vertigo. Medical practitioners are generally called upon to decide whether or not there is a reasonable medical purpose to use of BZD or opiates. In as much as these drugs are used to treat subjective sensations, these decisions generally have no basis in objective data, and depend on "judgement" calls. One wonders whether this decision is properly the province of all medical providers that can prescribe. The author feels that prescription of these drugs is properly the province of the doctor that knows the patient the best -- generally the primary care physician or internist.
Lader et al (1999) suggested that "The BZD are now recognized as major drugs of abuse and addiction. Other drug and non-drug therapies are available and have a superior risk benefit ratio in long-term use. It is concluded that BZD should be reserved for short-term use--up to 4 weeks--and in conservative dosage. "
The author of this page, holds the opinion that medical use of BZD should be restricted to "low doses" -- i.e. presumably the same as "conservative dosage" mentioned by Lader above, as well as in the table above. There are rarely patients where doses greater than low doses seem justified - -these are generally people who have clear and objective signs of vertigo (i.e. strong nystagmus), that has not responded to other management. When patient's refuse reasonable medical management -- for example a surgical procedure to eliminate vertigo -- in favor of benzodiazepine usage, this creates an ethical problem that is best resolved by a sensible clinician. There is no iron clad rule -- and just because a problem can be eliminated by surgery, doesn't mean that surgery should necessarily replace medications that work reasonably well.
Dr. Hain also feels that BZD should not be "first treatment" for dizziness, but rather should be part of a "stepped" protocol, beginning with alternatives (such as anticholinergic drugs -- usually meclizine). Individuals who are also taking other drugs that are often abused, such as opiates, are at higher risk, and prescriptions should be more limited. All of this being considered, there nevertheless are some patients who function well on low doses of BZD, and who are unable to function (e.g. work) without them. We think that "less harm" is done by continuing treatment than stopping.
Suicide risk is increased:
According to Blaze (2022), "Dodds et al (2017) reviewed 17 studies and found that use of BZDs are an independent risk factor for suicide; may be mediated through paradoxical reactions, increased aggression, and behavioral disinhibitions; often associated with clonazepam in the first month after prescription; Sun et al (2016) found zolpidem to be associated with increased risk for suicide. "Perhaps there is also a greater tendency of persons with some thoughts about suicide, to seek out BZD.
Falls are increased
BZDs are associated with falls (Leipzeig et al, 1999). This is hardly surprising -- they are often taken at night to induce sleep after all. One would think that any drug taken to induce sleep would increase falls. Leipzeig et al reported that the relative risk for both benzodiazepines and sedatives is roughly 1.5 fold. We would expect that meclizine is also associated with increased risk of falls as it is sedating.
Cognitive decline -- ?
Cognitive impairment and dementia: Again from Blaze (2022), "studies have found that BZDs and Z drugs increase the risk for dementia; however, some recent studies, e.g., Osler et al (2020), found no association between BZDs and Z drugs and dementia in 235,000 patients; some results were compatible with a protective effect; a review by Ferreira et al (2022) suggested an association between BZDs and cognitive decline in older adults. "
Perhaps related to cognitive decline, there is an increased risk of motor vehicle accidents as well.
BZD and Z drugs are considered PIMs -- potentially inappropriate medications, by the American Geriatric's society. This means that PCPs and internal medicine providers may consider it their mission to "deprescribe" BZD and Z drugs, especially in persons considered to be "geriatric".
Curiously, deprescribing of benzodiazepines usually doesn't work long term. 82% to 86% of patients who successfully complete a BZD taper "relapse" in ≤15 mo.
OK -- so how is this done ?
Soyka et al (2017) recommended converting to a long-acting BZD followed by 4 to 12 wk taper (10% to 50% reduction in dosage); According to Blaze (2022), "no clinical data exist that demonstrate a benefit to changing to a long-acting BZD; tapering may be best for patients without use disorders; withdrawal symptoms during tapering should be treated with supportive measures" (i.e. not another BZD). One would expect that a long acting benzodiazepine might cause a less "bumpy" withdrawal.
Ries (1998) recommended a regimen for inpatients consisting of a rapid taper of BZDs over 3 days and use of other drugs; antiepileptic drugs (e.g., depakote, carbamazepine, gabapentin) administered during the taper. This is a rather old paper, and these days oxcarbazepine is thought to be superior to carbamazepine, and gabapentin is not the best seizure drug. Accordingly, this is generally not done. Instead, in the outpatient setting, doses are gradually reduced over months. One usually does not go "cold turkey" with these drugs. This can cause problems -- if a PCP decides to stop prescribing, with no mechanism to handle the withdrawal, there can be danger.
According to Blazes (2022) "On stopping, there often is the "PAWs" syndrome -- post-acute withdrawal syndrome (PAWS) — a set of impairments that may persist for weeks, months or years; 90% of patients who experience withdrawal develop PAWS; symptoms (e.g., "benzo brain" [cognitive difficulties, forgetfulness, irritability, pessimism, apathy, hypersensitivity to sensory stimuli]) may wax and wane; misdiagnosis as personality disorder is common; treatment of PAWS with antiepileptic agents is supported by clinical data; oxcarbazepine has the preferred adverse effect profile and is easiest to dose; gabapentin may be prescribed at 100 to 300 mg, 3 doses/day; treatment may last for 6 mo to 1 yr.; nonpharmacologic treatment — e.g., behavioral therapy, group therapy, 12-step therapy, acupuncture"