THERAPY IN PRACTICE CNS Drugs 2003; 17 (2): 85-100

1172-7047/03/0002-0085/$30.00/0

© Adis International Limited. All rights reserved.

Pharmacological Treatment of Vertigo

Timothy C. Hain and Mohammed Uddin
Departments of Neurology, Otolaryngology and Physical Therapy and Human Movement
Sciences, Northwestern University, Chicago, Illinois, USA

Contents
Abstract . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 85
1. Physiology of Vertigo . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 86
2. Neurochemistry of Vertigo . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 87
3. Drugs Used in the Treatment of Vertigo . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 88
3.1 Vestibular Suppressants . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 88
3.1.1 Anticholinergics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 88
3.1.2 Antihistamines . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 89
3.1.3 Benzodiazepines . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 89
3.1.4 Calcium Channel Antagonists . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 89
3.2 Antiemetics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 90
3.3 Agents That Affect the Rate of Compensation . . . . . . . . . . . . . . . . . . . . . . . . . . . 91
3.4 Agents of Uncertain Efficacy and Mechanism . . . . . . . . . . . . . . . . . . . . . . . . . . . 91
4. Drug Treatment of Individual Conditions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 92
4.1 Benign Paroxysmal Positional Vertigo . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 92
4.2 Ménière’s Disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 93
4.2.1 Episodic Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 93
4.2.2 Prophylaxis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 93
4.3 Vestibular Neuritis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 94
4.4 Bilateral Vestibular Paresis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 94
4.5 Central Vertigo . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 95
4.6 Psychogenic Vertigo . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 96
4.7 Treatment of Undetermined and Ill-Defined Causes of Vertigo . . . . . . . . . . . . . . . . . 97
5. Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 97

Abstract This review discusses the physiology and pharmacological treatment of ver-
tigo and related disorders. Classes of medications useful in the treatment of ver-
tigo include anticholinergics, antihistamines, benzodiazepines, calcium channel
antagonists and dopamine receptor antagonists. These medications often have
multiple actions. They may modify the intensity of symptoms (e.g. vestibular
suppressants) or they may affect the underlying disease process (e.g. calcium
channel antagonists in the case of vestibular migraine). Most of these agents,
particularly those that are sedating, also have a potential to modulate the rate of
compensation for vestibular damage. This consideration has become more rele-
vant in recent years, as vestibular rehabilitation physical therapy is now often
recommended in an attempt to promote compensation. Accordingly, therapy of
vertigo is optimised when the prescriber has detailed knowledge of the pharma-
86 Hain & Uddin

cology of medications being administered as well as the precise actions being

sought.
There are four broad causes of vertigo, for which specific regimens of drug
therapy can be tailored. Otological vertigo includes disorders of the inner ear such
as Ménière’s disease, vestibular neuritis, benign paroxysmal positional vertigo
(BPPV) and bilateral vestibular paresis. In both Ménière’s disease and vestibular
neuritis, vestibular suppressants such as anticholinergics and benzodiazepines are
used. In Ménière’s disease, salt restriction and diuretics are used in an attempt to
prevent flare-ups. In vestibular neuritis, only brief use of vestibular suppressants
is now recommended. Drug treatments are not presently recommended for BPPV
and bilateral vestibular paresis, but physical therapy treatment can be very useful
in both. Central vertigo includes entities such as vertigo associated with migraine
and certain strokes. Prophylactic agents (L-channel calcium channel antagonists,
tricyclic antidepressants, β-blockers) are the mainstay of treatment for migraine-
associated vertigo. In individuals with stroke or other structural lesions of the
brainstem or cerebellum, an eclectic approach incorporating trials of vestibular
suppressants and physical therapy is recommended. Psychogenic vertigo occurs
in association with disorders such as panic disorder, anxiety disorder and agora-
phobia. Benzodiazepines are the most useful agents here. Undetermined and ill-
defined causes of vertigo make up a large remainder of diagnoses. An empirical
approach to these patients incorporating trials of medications of general utility,
such as benzodiazepines, as well as trials of medication withdrawal when appro-
priate, physical therapy and psychiatric consultation is suggested.

1. Physiology of Vertigo only rarely a consequence of visual or somatosen-

Vertigo is the illusion of rotational motion.
Most vertigo with definable cause is otological,
caused by dysfunction of the rotational velocity
sensors of the inner ear, the semicircular canals.
For consideration of other types of vertigo, it is
helpful to consider how the brain processes motion
signals. In the normal situation, individuals contin-
uously process three types of sensory input: vestib-
ular (inner ear), visual and somatosensory. These
three streams of information are combined in the
central vestibular apparatus to form an estimate of
orientation and motion of the head and body. Phys-
iological and pathological vertigo is caused by
asymmetrical input into the central vestibular ap-
paratus or asymmetrical central processing.[1]
Accordingly, possible sources of vertigo in-
clude all possible combinations of sensory distur-
bances related to motion as well as malfunction of
the central vestibular apparatus. Practically, how-
ever, because the visual and somatosensory senses
mainly produce position-coded signals, vertigo is
sory malfunction. An example of ‘visual vertigo’
might be vertigo associated with an oculomotor
disturbance accompanied by nystagmus. Neverthe-
less, the common varieties of visual disturbance,
diminished vision, double vision or disorders of the
accommodation system usually do not create ver-
tigo. Similarly, vertigo is only occasionally asso-
ciated with somatosensory dysfunction, as in cer-
vical vertigo. Central vertigo is more frequent than
nonvestibular sensory vertigo but still uncommon
compared with otological vertigo, as is discussed
in more detail in section 4.
When planning treatment, the symptom of ver-
tigo should be differentiated from motion sickness,
which is the malaise and nausea that may follow
real or illusory sensations of motion. Motion sick-
ness can be caused by a mismatch of sensory sig-
nals as well as malfunction of central structures
involved in comparison between senses encoding
motion. Vertigo and motion sickness are not syn-
onymous. For example, carnival rides frequently

© Adis International Limited. All rights reserved. CNS Drugs 2003; 17 (2)
Treatment of Vertigo
elicit illusory rotational sensations, but motion
sickness can often be avoided. Also, the symptoms
of motion sickness usually persist longer and tend
to be more disturbing than the inciting vertigo.
Again, although normal individuals experiencing
similar sensory disturbances reliably experience
vertigo, susceptibility to motion sickness varies re-
markably. In addition, the pharmacological man-
agement of vertigo and motion sickness are clearly
distinct.[2,3]
Finally, when planning treatment, recovery and
compensation must also be considered. Every ves-
tibular stimulus, whether the result of natural mo-
tion or disease, has the potential to initiate a process
of compensatory adaptation. The pharmacological
management of compensation is distinct from that
of vertigo and motion sickness and, in fact, agents
that relieve vertigo or motion sickness often block
compensation. There are two key concepts regard-
ing compensation that need to be considered when
planning therapy of vertigo. First, promotion of
central compensation is desirable during the pro-
cess of recovery from persistent vestibular imbal-
ance, such as after a severe bout of vestibular neu-
ritis (see section 4.3). Second, prevention of
unneeded and counterproductive compensation
may be desirable after a transient vestibular imbal-
ance, such as might be caused by Ménière’s dis-
ease (see section 4.2).
2. Neurochemistry of Vertigo
There are at least six neurotransmitters of the
vestibular system involved in the three-neuron arc
between the vestibular hair cells and oculomotor
nuclei that drives the vestibulo-ocular reflex (see
table I). There are also a host of other neurotrans-
mitters that modulate function or are involved in a
more minor way.
Glutamate (and aspartate) is an excitatory trans-
mitter at all three neurons in the arc.[4,5] Alpha-
amino-3-hydroxy-5-methylisoxazole-4-proprionic
acid (AMPA)–type glutamate receptors are thought
to mediate synaptic transmission, as they do in most
regions of the CNS. N-methyl-D-aspartate (NMDA)–
type glutamate receptors appear to contribute to
© Adis International Limited. All rights reserved.
87
both maintenance of resting discharge of central
vestibular neurons as well as possibly long-term
modulation of synaptic transmission in the central
vestibular structures.[5]
Acetylcholine is both a peripheral and central
agonist affecting muscarinic receptors. However,
peripherally acetylcholine appears only to be in-
volved in the brainstem efferent–hair cell synapse,
which has an uncertain functional significance.
Acetylcholine appears to function centrally as an
excitatory neurotransmitter. Both nicotinic and
muscarinic cholinergic receptors have been dem-
onstrated in all vestibular nuclei with the highest
density within the medial vestibular nuclei.[5] Lo-
cal injection of cholinergic agonists into the ves-
tibular nuclei induces a postural syndrome in intact
animals that closely resembles the postural syn-
drome following hemilabyrinthectomy. Acetyl-
choline is involved with compensation. In animals
that have compensated for vestibular deficits, sys-
temic injection of cholinomimetics induces the re-
appearance of postural asymmetries.[6] Of five sub-
types of acetylcholine receptors presently known,
receptors found in the pons and medulla, presum-
ably those involved with dizziness, are almost ex-
clusively of the muscarinic M2 subtype.[7]
γ-Aminobutyric acid (GABA) is thought to be
the inhibitory neurotransmitter for the commis-
sures in the medial vestibular nucleus as well as
being the inhibitory neurotransmitter between the
cerebellar Purkinje cells and lateral vestibular nu-
cleus.[8] Stimulation of the two types of GABA
receptors, GABAA and GABAB, have similar in-
hibitory effects on vestibular pathways.[9] Specific
Table I. Neurotransmitters of the vestibular system
Neurotransmitter Peripheral role Central role
Glutamate Excitatory Excitatory
Acetylcholine Excitatory for efferent synapse Excitatory
GABA Unclear Inhibitory
Dopamine Excitatory
Noradrenaline Modulator
(norepinephrine)
Histamine Unclear
GABA = γ-aminobutyric acid.
CNS Drugs 2003; 17 (2)
88
GABAB agonists, such as baclofen, decrease the
duration of vestibular responses in animal mod-
els.[10] GABA is also the inhibitory neurotransmit-
ter for the vertical vestibulo-ocular system, whereas
glycine serves for the horizontal vestibulo-ocular
system.[11]
The mechanisms of action of several other neuro-
transmitters known to be important targets in the
pharmacological management of vertigo are less
well understood. Histamine is found diffusely in
central vestibular structures. Histamine does not
appear to be a neurotransmitter in the peripheral
vestibular system.[12] Centrally acting antihista-
mines modulate symptoms of motion sickness.[2]
Stimulation of histamine H1 and H2 receptors ex-
cites central medial vestibular nucleus neurons.[4,5]
H3 is an autoreceptor that inhibits histamine release.
Noradrenaline (norepinephrine) modulates the in-
tensity of central reactions to vestibular stimula-
tion[13] and facilitates compensation. Centrally act-
ing adrenergic drugs such as amphetamine and
ephedrine have a prophylactic effect against mo-
tion sickness.[13] Dopamine may accelerate vestib-
ular compensation to unilateral labyrinthectomy,
and dopamine blockers may delay recovery.[14]
The neurochemistry of emesis overlaps in part
with the neurochemistry of vertigo and motion
sickness. Acetylcholine and histamine are excit-
atory neurotransmitters involved in the central
control of emesis.[3] GABA receptor agonists in-
hibit central emesis reflexes as well as cortical
pathways involved in anticipatory vomiting. Dopa-
mine is more important in emesis than vertigo as it
is an excitatory central neurotransmitter in the che-
moreceptor trigger zone and vomiting centre and
is involved peripherally in modulating gut motil-
ity. Serotonin is also important in emesis but plays
little or no role in vertigo and a minor role in mo-
tion sickness.[15,16] Selective agents that block the
serotonin 5-HT3 receptor subtype reduce nausea
and emesis through a combined action on central
reflexes and peripheral receptors.[17]
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Hain & Uddin
3. Drugs Used in the Treatment
of Vertigo
Vestibular suppressant and antiemetic drugs are
the mainstay of treatment of vertigo.
3.1 Vestibular Suppressants
Vestibular suppressants are drugs that reduce
nystagmus evoked by a vestibular imbalance. Con-
ventional vestibular suppressants consist of three
major drug groups: the anticholinergics, the anti-
histamines and the benzodiazepines (see table II).
We will also discuss use of calcium channel antag-
onists for vestibular suppression, although their
use for this purpose currently is not accepted uni-
versally.
3.1.1 Anticholinergics
Anticholinergics are central vestibular suppres-
sants that suppress firing in vestibular nucleus neu-
rons of animals[18] and reduce the velocity of ves-
tibular nystagmus in humans.[19-22] In spite of a
study suggesting effectiveness of glycopyrrolonium
bromide (glycopyrrolate) in Ménière’s disease,[23]
as acetylcholine is not a peripheral neurotransmit-
ter in vestibular afferents it seems unlikely that anti-
cholinergics that have no central action are useful
for vestibular suppression.
Anticholinergics are also useful for managing
motion sickness. Scopolamine, for example, in-
creases motion tolerance.[13] Agents with central
anticholinergic effects are most important, because
anticholinergic drugs that do not cross the blood-
brain barrier are ineffective in controlling motion
sickness.[2] Unlike antihistamines, which are dis-
cussed is section 3.1.2, pure anticholinergics are
ineffective for motion sickness if administered af-
ter symptoms have already appeared.
All anticholinergics conventionally used in the
management of vertigo or motion sickness have
prominent adverse effects, often including a dry
mouth, dilated pupils and sedation. Scopolamine
and atropine are nonspecific muscarinic receptor
antagonists.[7] It is to be hoped that agents selective
for vestibular subtypes of muscarinic receptors
will eventually be developed or discovered among
CNS Drugs 2003; 17 (2)
Treatment of Vertigo
Table II. Vestibular suppressants, arranged in order of preference from most to least commonly used (oral doses unless otherwise stated)
Drug Dosea
Meclozine Oral tablets 12.5–50mg every 4-6h Antihistamine, anticholinergic
or chewable tablets 25mg tid
Clonazepam 0.5mg bid
Scopolamine 0.5mg patch every 3 days
Dimenhydrinate 50mg every 4–6h
Diazepam 2–10mg (one dose) given acutely
orally, IM or IV or 2mg orally bid
Lorazepam 0.5mg bid
a Doses are all those used routinely for adults and generally will not be appropriate for children.
bid = twice daily; IM = intramuscularly; IV = intravenously; tid = three times daily.
our currently available pharmacopoeia, as these
agents may provide vestibular suppression with
fewer adverse effects.
The transdermal preparation of scopolamine
deserves some special comment. The transdermal
delivery method has a great advantage in that it
bypasses the stomach, making it effective in situ-
ations where gastric absorption may be erratic. The
main problem is skin irritation, which usually pre-
cludes long-term usage. Anticholinergic adverse
effects such as dry mouth and blurred vision also
limit use. Occasional patients become dependent
on scopolamine patches and develop withdrawal
symptoms (usually nausea and vertigo) when it is
discontinued.[24]
3.1.2 Antihistamines
All the antihistamines in general use for control
of vertigo also have substantial anticholinergic ac-
tivity, and it seems likely that most or all of their
vestibular suppressant effect derives from their anti-
cholinergic action. It is well accepted, however,
that centrally acting antihistamines can prevent
motion sickness and reduce the severity of its
symptoms even if taken after the onset of symp-
toms.[2] Antihistamines that do not cross the blood-
brain barrier are not used to treat vertigo. Little is
known about the effect of drugs that affect hista-
mine on vestibular compensation.
3.1.3 Benzodiazepines
Benzodiazepine drugs are GABA modulators, act-
ing centrally to suppress vestibular responses.[25,26]
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89
Pharmacological class Adverse reactions
Sedating, precaution in prostatic enlargement
Benzodiazepine Mildly sedating, drug dependency
Anticholinergic Topical allergy, precaution in glaucoma,
tachyarrhythmia, prostatic enlargement
Antihistamine, anticholinergic Sedating, precaution in prostatic enlargement
Benzodiazepine Sedating, respiratory depressant, drug
dependency, precaution in glaucoma
Benzodiazepine Mildly sedating, drug dependency
In small doses, benzodiazepines are extremely use-
ful for management of vertigo. They are also useful
in prevention of motion sickness.[27] Habituation,
impaired memory and increased risk of falling are
the main problems. Although it has been suggested
that benzodiazepine treatment might impair com-
pensation for vestibular lesions, experimental data
have not borne this out.[28]
Lorazepam is a particularly useful agent be-
cause of its effectiveness and simple kinetics. Lor-
azepam has no active metabolites. Habituation, the
biggest problem,[29] can be avoided by keeping the
dose to 0.5mg twice a day or less. Lorazepam can
also be taken sublingually (1mg) for an acute at-
tack of vertigo. For brief bouts of vertigo, such as
are typically found in Ménière’s disease, loraze-
pam usually can be discontinued after a few days.
Low doses of diazepam (2mg twice a day) can be
used similarly. Relatively little information is
available about habituation potential and efficacy
of clonazepam, but it appears as effective as a ves-
tibular suppressant as lorazepam.[30] It is also usu-
ally prescribed in a dose of 0.5mg twice a day. The
authors prefer to avoid use of alprazolam for ves-
tibular suppression because of the potential for a
difficult withdrawal syndrome. Long-acting ben-
zodiazepines are usually not helpful for relief of
vertigo.
3.1.4 Calcium Channel Antagonists
Calcium channel antagonists may have utility
in the treatment of dizziness. Two examples of this
group, flunarizine and cinnarizine, are popular
CNS Drugs 2003; 17 (2)
90
antivertiginous agents outside of the USA.[31,32]
Nimodipine has recently been reported as possibly
effective in Ménière’s disease[33] as well as in al-
leviating peripheral vertigo.[34]
There are several reasons why calcium channel
antagonists might be of help in the management of
vertigo. Some calcium channel antagonists have
been shown to be vestibular suppressants.[31,35]
Vestibular dark cells also contain calcium chan-
nels, suggesting the possibility that calcium chan-
nel antagonists might change ion concentration in
endolymph.[36] Practically, some calcium channel
antagonists, such as verapamil, have strong consti-
pating effects, which may be helpful in managing
diarrhoea caused by vestibular imbalance. Cal-
cium channel antagonists also often have anticho-
linergic and/or antihistaminic activity.[37] Finally,
calcium channel antagonists may be effective in
‘vestibular Ménière’s’, as individuals with this di-
agnosis have a high prevalence of migraine,[38] for
which calcium channel antagonists are often effec-
tive.[39]
3.2 Antiemetics
Table III lists the drugs that are commonly used
for control of nausea in patients with vertigo. The
choice of agent depends on consideration of the
route of administration and the adverse effect pro-
file. The oral agents are used for mild nausea. Sup-
Table III. Antiemetics for use in vertigo, arranged in alphabetical order
Drug Usual adult dosea
Granisetron 1mg orally or IV
Meclozine 12.5 or 25mg orally every 4–6h or tid;
25mg chewable tablet tid
Metoclopramide 10mg orally tid or 10mg IM
Ondansetron 4mg orally or IV
Prochlorperazine 5 or 10mg IM or orally every 6–8h or
25mg rectally every 12h
Promethazine 25mg orally every 6–8h, 25mg rectally
every 12h or 12.5mg IM every 6–8h
Thiethylperazine 10mg orally or IM up to tid
Trimethobenzamide 250mg orally tid, 200mg IM tid or 200mg
rectally tid
a Doses are all those used routinely for adults and generally will not be appropriate for children.
IM = intramuscularly; IV = intravenously; tid = three times daily.
© Adis International Limited. All rights reserved.
Hain & Uddin
positories are commonly used in outpatients who
are unable to absorb oral agents because of gastric
atony or vomiting. Sublingual administration is
also useful. Injectables are used in the emergency
room or inpatient settings.
Some antihistamines commonly used as vestib-
ular suppressants have significant antiemetic prop-
erties (e.g. meclozine). When an oral agent is ap-
propriate, meclozine is generally the first to be
used, because it rarely causes adverse effects any
more severe than drowsiness. A combination of an
antihistamine (doxylamine) and pyridoxine (vita-
min B6) is presently marketed for nausea associ-
ated with pregnancy.
Phenothiazines, such as prochlorperazine and
promethazine, are effective antiemetics, probably
because of their dopamine receptor antagonist ac-
tivity, but they also act at other sites. For example,
promethazine is also an H1 and muscarinic receptor
antagonist. Because these drugs can induce signif-
icant adverse effects, such as dystonia, they are
considered second-line drugs whose use should be
brief and cautious. Dopamine antagonists such as
the phenothiazines also have the potential to slow
vestibular compensation.[14]
Drugs that speed gastric emptying, such as
metoclopramide, a dopamine antagonist, and pow-
dered ginger root may be helpful in managing em-
esis.[40] Although metoclopramide is a potent cen-
Pharmacological class Adverse reactions
Serotonin 5-HT3 antagonist Headache
Antihistamine, anticholinergic Sedating, precautions in
glaucoma, prostate enlargement
Dopamine antagonist, stimulates Restlessness or drowsiness,
upper gastrointestinal motility extrapyramidal
Serotonin 5-HT3 antagonist Headache, diarrhoea, fever
Phenothiazine Sedating, extrapyramidal
Antihistamine Sedating, extrapyramidal
Phenothiazine Sedating, extrapyramidal
Similar to phenothiazine Sedating, extrapyramidal
CNS Drugs 2003; 17 (2)
Treatment of Vertigo
tral antiemetic, it is ineffective in preventing mo-
tion sickness.[41] Domperidone, a peripherally acting
dopamine D2 receptor antagonist, has antiemetic
activity as a result of peripheral gastrokinetic ac-
tion as well as central action on the chemoreceptor
trigger zone. It has similar efficacy to metoclopra-
mide combined with a more favourable safety pro-
file.[42] It is not available in the USA. All of these
medications, being dopamine antagonists, proba-
bly slow vestibular compensation.
5-HT3 antagonists such as ondansetron are
highly effective antiemetics that are also some-
times effective in vestibular disorders that mani-
fest with nausea, including some central disor-
ders.[43] These agents do not appear to be helpful
in preventing motion sickness.[15] The high cost of
these agents currently limits their usefulness.
3.3 Agents That Affect the Rate
of Compensation
Although the manipulation of compensation or-
dinarily is not considered in clinical practice, it
seems reasonable to do so in the interest of improv-
ing patient outcomes. If a patient has a permanent
vestibular lesion, for instance an acoustic neuroma
or a persistent vestibular neuritis, it may be desir-
able to accelerate central compensation. On the
other hand, one might wish to retard compensation
in individuals with a transient vestibular lesion,
such as is often caused by Ménière’s syndrome, as
‘recovery’ nystagmus can be part of the clinical
picture.[44,45]
At this writing, there are few data regarding the
effect on clinical outcomes of pharmacological
agents that alter vestibular compensation.[46] Many
drugs used to treat vertigo are reported to affect the
rate of compensation to vestibular lesions in ani-
mal models.[46] Drugs that accelerate compensa-
tion are mainly stimulants, and drugs that retard
compensation are mainly sedatives. Most, if not
all, vestibular suppressants retard compensation.
Dopamine agonists accelerate compensation, and
antagonists slow compensation.[14] Adrenergic ag-
onists such as ephedrine and amphetamines occa-
sionally are used in combination with vestibular
© Adis International Limited. All rights reserved.
91
suppressants.[13] Although they are most often
used to counteract the sedative effects of vestibular
suppressants, these stimulants may also help by
promoting vestibular compensation. Amphetamines
have been shown to speed recovery of motor func-
tion in stroke.[47] Calcium channel antagonists such
as verapamil also may enhance compensation.[46]
It seems likely that antihypertensive agents, which
act through adrenergic blocking or depleting, may
slow vestibular compensation.
3.4 Agents of Uncertain Efficacy
and Mechanism
Many substances, procedures and devices have
been promoted as effective treatments of vertigo,
and many of these have no clear proof of efficacy.
The tendency to attribute curative properties to a
bewildering number of medications and proce-
dures has been particularly evident in the treatment
of Ménière’s disease.[48,49] It seems likely that
most of these agents have minor or no pharmaco-
logical efficacy, but they may function as place-
bos.
An intriguing member of this group is betahist-
ine. Whereas the antihistamines used in treating
vertigo are usually centrally acting H1 receptor an-
tagonists that are also muscarinic blockers (e.g.
meclozine), betahistine is an H1 receptor agonist
and H3 receptor antagonist.[50] It has been sug-
gested that betahistine decouples the negative
feedback loop controlling histamine release, re-
sulting in central facilitation of histaminergic
neurotransmission in the brain.[51] In therapeutic
doses, administration of betahistine is associated
with reduction in the gain of the vestibulo-ocular
reflex.[51,52] In addition, betahistine increases
blood flow to the inner ear.[53] It has also been sug-
gested that betahistine may accelerate compensa-
tion.[54] In the USA, however, as of 2002, the US
FDA does not recognise betahistine as an effective
medication. A recent review concluded that there
was insufficient evidence to say whether or not
betahistine had an effect in Ménière’s disease.[55]
Ginkgo biloba is promoted for the treatment of
Alzheimer’s disease, sexual dysfunction, depres-
CNS Drugs 2003; 17 (2)
92
sion, headache, claudication, vertigo and tinni-
tus.[56] Ginkgo biloba may reduce the viscosity of
the blood (literally blood thinning), and it also may
be an antioxidant. A recent study suggests that
Ginkgo biloba is similar in efficacy for vertigo as
betahistine.[57] Like Ginkgo biloba, Vertigoheel, a
homeopathic remedy, has recently been compared
with betahistine and found to be equivalent.[58]
Baclofen and amantadine, both centrally acting
agents used generally in conditions unrelated to
vertigo, are sometimes advocated for vertigo. Bac-
lofen is most commonly used in patients in whom
the diagnosis of microvascular compression of the
eighth nerve is being considered. Amantadine is
used in an attempt to promote compensation in in-
dividuals with brain injury.[59] As amantadine is a
dopamine agonist, it seems possible that it might
be useful. No formal studies of efficacy of these
drugs for treatment of vertigo and related condi-
tions are yet available.
4. Drug Treatment of
Individual Conditions
4.1 Benign Paroxysmal Positional Vertigo
Benign paroxysmal positional vertigo (BPPV)
is the single most common type of vertigo, ac-
counting for roughly 20% of all vertigo cases.[60]
BPPV is diagnosed by combining a history of po-
sitional vertigo with a typical nystagmus pattern
that appears on positional testing. It is currently
thought that BPPV is caused by the presence of free
otoconia or ‘canaliths’ within the semicircular ca-
nals, dislodged from the otolith organs by trauma,
infection or degeneration (see figure 1). The debris
moves to the lowest part of the posterior canal with
changes in head position and causes vertigo and
nystagmus as it tumbles. Symptoms can be very
intense, but fortunately they are brief, since dizzi-
ness occurs only while the debris shifts position.
Physical treatments based on manipulation of
the head are the most effective treatment for
BPPV.[61] Drugs are not nearly as helpful for BPPV
as are physical treatments, but antiemetics can be
helpful in patients whose vertiginous spells are fol-
© Adis International Limited. All rights reserved.
Hain & Uddin
lowed by nausea. Meclozine may also be an effec-
tive adjunct to the specific exercises for this con-
dition. In this situation, meclozine is taken prior to
the home exercise in an attempt to prevent motion
sickness and nausea. Ondansetron can be very
helpful in preventing emesis associated with diag-
nostic or therapeutic manoeuvres. In this situation,
an oral or sublingual dose of 4–8mg is given 30
minutes prior to the manoeuvre. Vestibular supp-
ressants that have little antiemetic activity (e.g. di-
azepam, lorazepam) are generally unable to reduce
day-to-day symptoms of BPPV to acceptable lev-
els.
Some patients with BPPV are conditioned by
the reliable appearance of vertigo with particular
positions and develop a phobia related to sleeping
on their back or on one side. The phobia can persist
for years after the inner ear condition has resolved.
This entity is called ‘phobic postural vertigo’. Pho-
bic postural vertigo is best treated with exercises,
such as the Brandt-Daroff exercises,[62] that are
desensitising rather than with vestibular suppress-
ant medications. Benzodiazepines can be helpful
in individuals with phobic postural vertigo who
Posterior
semicircular
canal
Utricle
Vestibule
Cupulolithiasis, debris Canalithiasis, debris
attached to cupula in posterior canal
Fig. 1. Canalithiasis mechanism of benign paroxysmal positional
vertigo (reproduced with permission from Dr T. Hain).
CNS Drugs 2003; 17 (2)
Treatment of Vertigo
otherwise might refuse to participate in the de-
sensitisation procedures.
4.2 Ménière’s Disease
Ménière’s disease is the second most common
cause of vertigo of otological origin. It is classi-
cally attributed to dilation and periodic rupture of
the endolymphatic compartment of the inner ear
(see figure 2). The pathognomonic symptoms in-
clude fluctuating hearing, roaring tinnitus, aural
fullness and tinnitus.[63]
4.2.1 Episodic Treatment
For the episodic vertigo that is common in
Ménière’s syndrome, vestibular suppressants with
or without an antiemetic (table II and table III) are
used to treat the acute attack, and no medications
are used in the interim. These agents do nothing to
correct the vestibular imbalance that causes the
symptoms, but they suppress the manifestations of
the imbalance (vertigo and nausea). Meclozine, di-
azepam, lorazepam and clonazepam are the most
useful suppressant agents for mild attacks (see ta-
ble II for doses). Intramuscular promethazine or
prochlorperazine and intravenous diazepam are
used in the emergency department or inpatient set-
ting for treatment of severe attacks. Otherwise,
nausea is managed with sublingual or suppository
preparations. However, these are rarely required
because most patients have some warning involv-
ing a change in hearing or aural sensation and can
take meclozine or a similar preparation before the
full-blown attack appears.
4.2.2 Prophylaxis
There is no consensus on prophylaxis of
Ménière’s syndrome,[62,64] and simply treating the
symptoms is considered acceptable. No matter
what prophylactic treatment is used, remission
eventually occurs in 60–80% of cases.[48,49] Be-
cause of the great variability in the course of
Ménière’s disease, to have adequate power a clin-
ical trial requires very large numbers, and very few
of these have been performed.
However, it is common practice to advise diet-
ary salt restriction (1–2g salt diet) and use of a mild
© Adis International Limited. All rights reserved.
93
Endolymphatic sac
Endolymphatic duct
Utricle
Saccule
Stapes
Fig. 2. Engorged endolymphatic compartment of the inner ear in
Ménière’s disease (reproduced with permission from Northwestern
University, Chicago, IL, USA).
diuretic such as hydrochlorothiazide/triamterene
(Dyazide®1 or Maxide®), as it is felt that this regi-
men may reduce the frequency of attacks. It should
be noted that Dyazide® may cause significant hy-
ponatraemia, especially in the elderly and in those
who are already salt restricted; in this situation, one
may wish to use an every-other-day dose schedule
and/or monitor serum electrolytes. The Maxide®
form of the drug is scored and can be broken in half.
In patients who cannot tolerate hydrochlorothiazide/
triamterene, diuretics that inhibit carbonic an-
hydrase, such as acetazolamide or methazolamide,
are occasionally helpful. Spironolactone may be
used in women with perimenstrual flare-ups. Cal-
cium channel antagonists such as verapamil may
also be helpful, although very few formal studies
of efficacy are available.[33]
Patients are also encouraged to avoid caffeine
and stop smoking. Daily use of vestibular suppres-
sants, as a prophylactic treatment, is generally dis-
couraged out of concern that they may impair ves-
tibular compensation. Some authors recommend a
1 Use of tradenames is for product identification only and
does not imply endorsement.
CNS Drugs 2003; 17 (2)
94
brief course of corticosteroids, especially if a sur-
gical treatment is being considered.[65]
4.3 Vestibular Neuritis
Vestibular neuritis is a monophasic, self-limited
condition that presents with vertigo, nausea, ataxia
and nystagmus.[66] These symptoms are brought
about by an acute imbalance in vestibular tone
combined with directionally asymmetrical re-
sponse to head rotation. Vestibular neuritis is thought
to be caused by a viral infection of the vestibular
portion of the eighth cranial nerve. Mumps and
various types of herpes viruses are possible infec-
tious agents.
A peculiar aspect of this condition is that hear-
ing is not impaired; the viral infection is hypothe-
sised to selectively affect vestibular fibres of the
eighth nerve, sparing the neighbouring fibres car-
rying cochlear information. When hearing is also
affected, the syndrome is termed ‘labyrinthitis’.
Similar presentations can arise from noninfectious
aetiologies, such as vascular compromise.
Evidence suggests that almost all patients with
vestibular neuritis have satisfactory resolution of
their symptoms as a result of a combination of re-
covery of function and central compensation.[66]
Severe distress associated with constant vertigo,
nausea and malaise usually lasts 2 or 3 days. Many
patients are ready to return to their regular activi-
ties after a week, and it is likely that in these in-
stances there has been only a transient and incom-
plete vestibular lesion. However, a substantial
proportion of patients may take as long as 2 months
to improve. On subsequent testing, this group often
is demonstrated to have a continued unilateral pa-
ralysis of vestibular function.
Unfortunately, it is not possible to predict
whether a patient will have a transient vestibular
imbalance and recover quickly or a permanent loss
of function associated with a poorer prognosis. The
implication for treatment is that if a permanent ves-
tibular imbalance is made more tolerable by a ves-
tibular suppressant medication or if central com-
pensation is partially blocked by a benzodiazepine
or agent with dopamine receptor blocking activity,
© Adis International Limited. All rights reserved.
Hain & Uddin
the patient may not recover as rapidly as otherwise.
Even bedrest may be poorly conceived, since ani-
mal studies have shown that immobilisation delays
recovery from experimental vestibular lesions.[67]
Thus, the treatment strategy for vestibular neu-
ritis involves use of as few medications as possible
and encouraging activity as much as is practical. In
the first few days of the illness, patients usually
severely restrict their activities, as rapid head
movements and activities such as sitting up or turn-
ing over in bed may cause increased vertigo. Ves-
tibular suppressants and antiemetics are commonly
used at this point, prescribed as suppositories if
necessary. By the third day, it is usually possible
to greatly reduce usage of vestibular suppressants,
and the patient should be encouraged to increase
activity as tolerated.
Most patients recover completely within 2
months. Those that do not usually have a signifi-
cant fixed vestibular paresis combined with central
dysfunction that slows their compensation. For ex-
ample, patients with alcoholic cerebellar degener-
ation or individuals of advanced age may recover
much more slowly.[68,69] Such patients can benefit
from a programme of physical therapy incorporat-
ing gait training and visual-vestibular exercises.
Surgical treatment is not indicated for vestibular
neuritis.
4.4 Bilateral Vestibular Paresis
Bilateral vestibular paresis presents with os-
cillopsia, ataxia and mild vertigo.[70] Typically, pa-
tients have recently been treated for a serious in-
fection, most often osteomyelitis or peritonitis.
The infection is treated for several weeks with an
ototoxic antibacterial (of which gentamicin is the
most commonly encountered). The symptoms of
bilateral vestibular paresis, ataxia and oscillopsia
manifest themselves when the patient recovers
from their infection and tries to walk.
When examined, these patients can read the vi-
sion chart with their head still but lose at least four
lines of acuity when their head is gently oscillated
from side to side. They are unable to stand in the
tandem Romberg position (heel to toe, arms crossed)
CNS Drugs 2003; 17 (2)
Treatment of Vertigo
with eyes closed for 6 seconds. Hearing is gener-
ally little affected. Rotatory chair testing is the best
way to confirm this diagnostic impression.
The long-term prognosis of patients with oto-
toxicity is only fair. A lengthy exposure to an
aminoglycoside antibacterial such as gentamicin
can cause a loss of vestibular hair cells.[71] As there
is no mechanism for hair cell regeneration in hu-
mans, the loss is permanent. Nevertheless, unless
there is a superimposed cerebellar lesion, substan-
tial recovery is the rule. Most patients return to
productive work within 1–2 years of exposure, al-
though they continue to have impaired balance in
situations where other senses are not informative,
such as in the dark or while walking on an uneven
surface. Recovery is felt to be a result of a combi-
nation of CNS plasticity and sensory substitu-
tion.[72]
It is important to note that medications that re-
duce symptoms of other forms of otological ver-
tigo, such as the vestibular suppressants and most
antiemetics, generally make symptoms worse in
bilateral vestibular paresis. Vestibular suppres-
sants must be eliminated in the management of this
condition. It is also prudent to avoid medications
with potential vestibular suppressant activity, such
as calcium channel antagonists, and those that
have central anticholinergic adverse effects (e.g.
many of the tricyclic antidepressants). Patients
should be warned to avoid subsequent exposure to
ototoxic drugs, especially gentamicin and loop di-
uretics (e.g. furosemide, bumetanide and ethacrynic
acid). If a loop diuretic is necessary, bumetanide is
the least ototoxic.[73] These patients should also be
advised to avoid loud noises, as they are likely to
be more vulnerable to noise-induced hearing loss
than the general population. Theoretically, in indi-
viduals with some remaining vestibular function,
medications that promote central plasticity might
be helpful in treating bilateral vestibular paresis,
and those that retard compensation, such as dopa-
mine antagonists, would slow or prevent recovery.
Bilateral vestibular paresis often responds well
to physical therapy. No surgical treatment is cur-
© Adis International Limited. All rights reserved.
95
rently available for bilateral vestibular loss. Pros-
thetic devices are presently being developed.
4.5 Central Vertigo
Vertigo caused by CNS dysfunction, or ‘central
vertigo’, is unusual. In the emergency room setting
or otolaryngology clinic, a central cause of vertigo
is identified in less than 5% of cases. Even in neu-
rology settings, central vertigo typically accounts
for only about 20% of diagnoses in patients com-
plaining of vertigo.[74] Central vertigo is largely
caused by vascular disorders. In the authors’ expe-
rience, vertigo associated with migraine, stroke or
transient ischaemia accounts for the majority of
cases of central vertigo. A large number of individ-
ual miscellaneous neurological disorders, such as
seizures, multiple sclerosis, posterior fossa tu-
mours and the Arnold-Chiari malformation, make
up the remainder.
In central vertigo, a prolonged duration of
symptoms is common. Although patients with pe-
ripheral vestibular imbalance typically recover
within days to months, patients with central ver-
tigo may continue to be distressed by ataxia, nau-
sea and the illusion of motion for years. Presum-
ably, the persistence of symptoms in patients with
central vertigo reflects a defect in the central mech-
anisms that usually compensate for vestibular le-
sions.
A combination of headache and vertigo is a
common presentation, particularly in women in
their mid-30s. In most instances, these symptoms
are caused by vertebrobasilar migraine, and a pro-
phylactic drug should be tried. [75] A sustained-
release preparation of verapamil 120mg is often
effective.[39] If the patient does not tolerate vera-
pamil (constipation is the most common problem),
a trial of amitriptyline can be made. When treating
vertigo, amitriptyline is favoured over the newer
selective serotonin reuptake inhibitor (SSRI) fam-
ily of antidepressant medications because of its anti-
cholinergic and antihistamine activity. Pizotifen,
an antihistamine with a chemical structure similar
to the tricyclic antidepressants, can also be effec-
tive.[76] β-Blockers form the third line of treatment,
CNS Drugs 2003; 17 (2)
96
but do not have the vestibular suppressant effects
of verapamil and amitriptyline.[77] Valproic acid
can be used for migraine prophylaxis, but adverse
effects, including weight gain and hair loss, limits
its usefulness.[77] Some authors have suggested
that acetazolamide therapy may also be effective
in this situation, but its significant adverse effects
limit its usefulness.[78]
Another common presentation of central ver-
tigo is in patients with a known central lesion, for
whom the goal is to reduce symptoms of vertigo or
ataxia. Benzodiazepines such as lorazepam, clona-
zepam and diazepam are frequently helpful (see
table II for doses), but one must be wary of habit-
uation and physical dependence.[79] Meclozine
taken in a dose of 25mg twice daily is occasionally
successful. Dopamine blockers such as prochlor-
perazine can be tried. The antiemetic ondansetron
may be helpful when central vertigo does not re-
spond to the usual agents.[80] Similarly, occasional
patients with oculomotor signs localising to the
vestibulocerebellum are helped by acetazolamide
therapy.[81]
Carbamazepine or oxcarbazepine, in doses ap-
propriate for neuralgia or epilepsy, can be tried in
patients having vertigo combined with an abnor-
mal EEG or brief episodic symptoms, ‘quick spins’,
that have not responded to other medications.
Gabapentin, a glutamate blocker, may also be used
in this situation.[82] Baclofen is used similarly. In
this situation, also called ‘vestibular paroxysmia’,
one might be treating epilepsy, microvascular
compression of the eighth nerve, irritation of the
vestibular nerve caused by a neurotrophic virus,
postsurgical vestibular neuralgia or intrinsic brain-
stem lesions.[83] Gabapentin is also generally use-
ful as a suppressor of nystagmus.[82]
Physical therapy emphasising effective use of
appliances such as canes, walkers and footwear is
often useful.
4.6 Psychogenic Vertigo
Psychogenic vertigo is vertigo that is caused by
an independently diagnosable psychiatric problem
such as anxiety, depression, somatisation or malin-
© Adis International Limited. All rights reserved.
Hain & Uddin
gering. Psychiatric-associated vertigo is the co-
existence of an organic vertigo with an inde-
pendently diagnosable psychiatric condition, such
as anxiety, which might be comorbid or reactive.
Often ‘dizziness’ is a more appropriate term to use
in this situation than ‘vertigo’, as these patients
may not be able to define their symptoms in terms
of an inappropriate movement of the environment,
but rather use terms such as ‘light-headed’ or
‘woozy’.
Because of inadequacies of our diagnostic metho-
dology, it is difficult to determine the proportion
of these patients in the ‘dizzy’ population as it pres-
ents to the clinician or at large in the population.
Some authors indicate that as many as 50% of all
patients with dizziness have a ‘functional’ source
of complaints.[84] However, this large percentage
results from an algorithm where patients with no
findings on testing were assigned this diagnosis.
This process is obviously fraught with peril, given
that patients for whom the diagnostic process may
have failed are placed in the same category as those
who do indeed have a psychological origin of symp-
toms. In the first author’s practice, only about 5%
of patients are assigned the ‘psychogenic’ diagno-
sis. A high proportion of patients with chronic (or-
ganic) vertigo develop secondary reactive psychi-
atric complications such as panic disorder and
depression, which are important to treat on their
own merits.
Treatment is based on the psychiatric diagnosis.
Anxiety and panic are the most common diagno-
ses, and benzodiazepines are the mainstay of treat-
ment. As considerably larger doses of these medi-
cations are needed for anxiety than for vestibular
suppression, and because it is likely that these pa-
tients will need long-term treatment, psychiatric
referral can be very useful in these cases. SSRIs
can also be used, but they are less useful. Although
they have an advantage over the benzodiazepines
in that they are not habituating, SSRIs are not as
reliable as the benzodiazepines for management of
anxiety, and they can also contribute to nausea and
ataxia.[85,86]
CNS Drugs 2003; 17 (2)
Treatment of Vertigo
Depression is an extremely unusual cause of
vertigo. When it is very clear that depression is
significant, one of the SSRI family, such as sertral-
ine, may be used. These agents can result in some
minor nausea as well as increase anxiety, and for
this reason should be used with caution.[87,88] Al-
most all antidepressants increase ataxia.[89,90]
Somatisation syndrome and malingering are
also commonly encountered in patients with a po-
tentially disabling but subjective symptom such as
dizziness. No drug treatments are available for ei-
ther diagnosis. In these situations, the clinician’s
goal is to reduce inappropriate expense and use of
healthcare resources.
4.7 Treatment of Undetermined and
Ill-Defined Causes of Vertigo
Regardless of whether one is practising in the
emergency room, otolaryngology clinic, neurol-
ogy clinic or a general medical setting, variants of
unlocalisable diagnoses such as ‘unknown diagno-
sis’, ‘vasovagal’ syncope, ‘hyperventilation syn-
drome’, ‘post-traumatic vertigo’ and ‘nonspecific’
dizziness are the most common single ‘cause’ of
dizziness reported. Between 38 and 52% of diag-
noses fall in this category across many se-
ries.[74,84,91,92] The unifying feature of these diag-
noses is the lack of abnormality on otological and
neurological examinations.
Treatment is necessarily empirical in vertigo of
undetermined origin. In the first author’s practice,
we ask the patient to log their symptoms on a cal-
endar. Next, for patients already taking medica-
tion, we withdraw drugs that could affect the ves-
tibular system, recording symptoms over 2 or more
weeks. This strategy may identify individuals with
ataxia caused by medication. One must be very
careful in this situation not to eliminate a medica-
tion critical to the patient’s well being. For exam-
ple, when one withdraws an antihypertensive such
as a calcium channel antagonist that has vasodila-
tor properties, angina may be precipitated.
Several drugs are then tried. If the patient does
not respond to daily meclozine, this may be re-
placed by a small dose of clonazepam or lorazepam.
© Adis International Limited. All rights reserved.
97
It is generally difficult to exclude mild Ménière’s
disease, and salt restriction and a diuretic such as
hydrochlorothiazide/triamterene may be tried. A trial
of migraine prophylaxis with sustained-release
verapamil (120mg of a sustained-release prepara-
tion each morning) is sometimes helpful in patients
with dizziness and headaches or patients with the
diagnosis of ‘vestibular Ménière’s’. Carbamaze-
pine or oxcarbazepine is tried for the symptom of
‘quick spins’ alluded to in section 4.5. Gabapentin
is also a reasonable drug to try empirically for cen-
tral vertigo.
Patients who do not respond to the above re-
gimens are followed at 3- to 6-month intervals and
undergo yearly audiometric screenings. This is im-
portant, as occasionally the symptoms of individuals
with small acoustic neuromas or early Ménière’s
disease will evolve into an identifiable clinical pre-
sentation. It is often helpful to re-examine patients
quickly when there is an acute flare of symptoms,
as in this way one can sometimes diagnose inter-
mittent conditions that can have normal intercur-
rent examinations, such as BPPV and Ménière’s
disease.
5. Conclusion
Vertigo is caused by several broad categories of
illness. The most common forms of otological ver-
tigo are BPPV, Ménière’s disease, vestibular neu-
ritis and ototoxicity. Treatment of these disorders
may be very effective but depends critically on at-
taining the correct diagnosis. Central vertigo has a
poorer prognosis than otological vertigo, and the
approach to treatment is largely empirical. Psycho-
genic vertigo is difficult to diagnose, and the treat-
ment approach critically depends on the diagnosis.
Psychiatric referral will be needed in many of these
cases. The treatment of patients with dizziness of
unknown cause is also empirical. An organised and
methodical approach to management of these pa-
tients is essential to maximise patient satisfaction.
CNS Drugs 2003; 17 (2)
98
Acknowledgements
The authors have provided no information on sources of
funding or on conflicts of interest directly relevant to the
content of this review/study.
References
1. Baloh RW, Honrubia V. Clinical neurophysiology of the ves-
tibular system. Contemp Neurol Ser 1979; 18: 1-21
2. Takeda N, Morita M, Hasegawa S, et al. Neurochemical mech-
anisms of motion sickness. Am J Otolaryngol 1989; 10 (5):
351-9
3. Takeda N, Morita M, Hasegawa S, et al. Neuropharmacology
of motion sickness and emesis: a review. Acta Otolaryngol
Suppl 1993; 501: 10-5
4. Serafin M, Khateb A, Waele C, et al. In vitro properties of
medial vestibular neurones. In: Shimazu H, Shinoda Y, edi-
tors. Vestibular and brain stem control of eye, head, and body
movements. Basel: Karger AG, 1992: 111-21
5. de Waele C, Muhlethaler M, Vidal PP. Neurochemistry of the
central vestibular pathways. Brain Res Brain Res Rev 1995;
20 (1): 24-46
6. Bienhold H, Flohr H. Role of cholinergic synapses in vestibular
compensation. Brain Res 1980; 195 (2): 476-8
7. Barton JJ, Huaman AG, Sharpe JA. Muscarinic antagonists in
the treatment of acquired pendular and downbeat nystagmus:
a double-blind, randomized trial of three intravenous drugs.
Ann Neurol 1994; 35 (3): 319-25
8. Smith PF, Darlington CL. Pharmacology of the vestibular sys-
tem. Baillieres Clin Neurol 1994; 3 (3): 467-84
9. Van Neerven J, Pompeiano O, Collewijn H. Depression of the
vestibulo-ocular and optokinetic responses by intrafloccular
microinjection of GABA-A and GABA-B agonists in the rab-
bit. Arch Ital Biol 1989; 127 (4): 243-63
10. Cohen B, Helwig D, Raphan T. Baclofen and velocity storage:
a model of the effects of the drug on the vestibulo-ocular
reflex in the rhesus monkey. J Physiol 1987; 393: 703-25
11. Spencer RF, Wang SF, Baker R. The pathways and functions
of GABA in the oculomotor system. Prog Brain Res 1992; 90:
307-31
12. Smith PF, Darlington CL. Recent advances in the pharmacology
of the vestibulo-ocular reflex system. Trends Pharmacol Sci
1996; 17 (11): 421-7
13. Wood CD. Antimotion sickness and antiemetic drugs. Drugs
1979; 17 (6): 471-9
14. Petrosini L, Dell’Anna ME. Vestibular compensation is af-
fected by treatment with dopamine active agents. Arch Ital
Biol 1993; 131 (2-3): 159-71
15. Stott JR, Barnes GR, Wright RJ, et al. The effect on motion
sickness and oculomotor function of GR 38032F, a 5-HT3-
receptor antagonist with anti-emetic properties. Br J Clin
Pharmacol 1989; 27 (2): 147-57
16. Okada F, Torii Y, Saito H, et al. Antiemetic effects of sero-
tonergic 5-HT1A-receptor agonists in Suncus murinus. Jpn J
Pharmacol 1994; 64 (2): 109-14
17. Endo T, Minami M, Hirafuji M, et al. Neurochemistry and neuro-
pharmacology of emesis: the role of serotonin. Toxicology
2000; 153 (1-3): 189-201
18. Kirsten EB, Schoener EP. Action of anticholinergic and related
agents on single vestibular neurones. Neuropharmacology
1973; 12 (12): 1167-77
19. Pyykko I, Schalen L, Jantti V. Transdermally administered sco-
polamine vs. dimenhydrinate. I: effect on nausea and vertigo
© Adis International Limited. All rights reserved.
Hain & Uddin
in experimentally induced motion sickness. Acta Otolaryngol
1985; 99 (5-6): 588-96
20. Pyykko I, Padoan S, Schalen L, et al. The effects of TTS-
scopolamine, dimenhydrinate, lidocaine, and tocainide on
motion sickness, vertigo, and nystagmus. Aviat Space Envi-
ron Med 1985; 56 (8): 777-82
21. Pyykko I, Schalen L, Matsuoka I. Transdermally administered
scopolamine vs. dimenhydrinate. II: effect on different types
of nystagmus. Acta Otolaryngol 1985; 99 (5-6): 597-604
22. Shojaku H, Watanabe Y, Ito M, et al. Effect of transdermally
administered scopolamine on the vestibular system in hu-
mans. Acta Otolaryngol Suppl 1993; 504: 41-5
23. Storper IS, Spitzer JB, Scanlan M. Use of glycopyrrolate in the
treatment of Meniere’s disease. Laryngoscope 1998; 108
(10): 1442-5
24. Feder RE. Transdermal scopolamine withdrawal syndrome [let-
ter]. Clin Neuropharmacol 1999; 22 (2): 120
25. Padoan S, Korttila K, Magnusson M, et al. Reduction of gain
and time constant of vestibulo-ocular reflex in man induced
by diazepam and thiopental. J Vestib Res 1990; 1 (1): 97-104
26. Blair SM, Gavin M. Modifications of vestibulo-ocular reflex
induced by diazepam: experiments in the macaque. Arch
Otolaryngol 1979; 105 (12): 698-701
27. McClure JA, Lycett P, Baskerville JC. Diazepam as an anti-
motion sickness drug. J Otolaryngol 1982; 11 (4): 253-9
28. Martin J, Gilchrist DP, Smith PF, et al. Early diazepam treat-
ment following unilateral labyrinthectomy does not impair
vestibular compensation of spontaneous nystagmus in guinea
pig. J Vestib Res 1996; 6 (2): 135-9
29. Funderburk FR, Griffiths RR, McLeod DR, et al. Relative abuse
liability of lorazepam and diazepam: an evaluation in ‘recre-
ational’ drug users. Drug Alcohol Depend 1988; 22 (3): 215-22
30. Halmagyi M. Vertigo and vestibular disorders. In: Eadie MJ,
editor. Drug therapy in neurology. Edinburgh: Churchill Liv-
ingstone, 1992: 375-85
31. Lee JA, Watson LA, Boothby G. Calcium antagonists in the
prevention of motion sickness. Aviat Space Environ Med
1986; 57 (1): 45-8
32. Verspeelt J, De Locht P, Amery WK. Postmarketing study of
the use of flunarizine in vestibular vertigo and in migraine.
Eur J Clin Pharmacol 1996; 51 (1): 15-22
33. Lassen LF, Hirsch BE, Kamerer DB. Use of nimodipine in the
medical treatment of Meniere’s disease: clinical experience.
Am J Otol 1996; 17 (4): 577-80
34. Pianese CP, Hidalgo LO, Gonzales RH, et al. New approaches
to the management of peripheral vertigo: efficacy and safety
of two calcium antagonists in a 12-week, multinational, double-
blind study. Otol Neurotol 2002; 23 (3): 357-63
35. Aoki M, Ito Y, Miyata H. Prevention of vestibular deafferentation-
induced spontaneous nystagmus with pretreatment of Ca2+
channel/N-methyl-D-aspartic acid receptor antagonists in
guinea pigs. Acta Otolaryngol 1998; 118 (4): 554-6
36. Takeuchi S, Marcus DC, Wangemann P. Maxi K+ channel in
apical membrane of vestibular dark cells. Am J Physiol 1992;
262 (6 Pt 1): C1430-6
37. Rascol O, Clanet M, Montastruc JL. Calcium antagonists and
the vestibular system: a critical review of flunarizine as an
antivertigo drug. Fundam Clin Pharmacol 1989; 3: 79s-87s
38. Rassekh CH, Harker LA. The prevalence of migraine in Me-
niere’s disease. Laryngoscope 1992; 102 (2): 135-8
39. Solomon GD, Steel JG, Spaccavento LJ. Verapamil prophylaxis
of migraine: a double-blind, placebo-controlled study. JAMA
1983; 250 (18): 2500-2
CNS Drugs 2003; 17 (2)
Treatment of Vertigo
40. Grontved A, Brask T, Kambskard J, et al. Ginger root against
seasickness: a controlled trial on the open sea. Acta
Otolaryngol 1988; 105 (1-2): 45-9
41. Kohl RL. Failure of metoclopramide to control emesis or nau-
sea due to stressful angular or linear acceleration. Aviat Space
Environ Med 1987; 58 (2): 125-31
42. Barone JA. Domperidone: a peripherally acting dopamine2-
receptor antagonist. Ann Pharmacother 1999; 33 (4): 429-40
43. Macleod AD. Ondansetron in multiple sclerosis. J Pain Symp-
tom Manage 2000; 20 (5): 388-91
44. Bance M, Mai M, Tomlinson D, et al. The changing direction
of nystagmus in acute Meniere’s disease: pathophysiological
implications. Laryngoscope 1991; 101 (2): 197-201
45. McClure JA, Copp JC, Lycett P. Recovery nystagmus in Me-
niere’s disease. Laryngoscope 1981; 91 (10): 1727-37
46. Smith PF, Darlington CL. Can vestibular compensation be en-
hanced by drug treatment? A review of recent evidence. J
Vestib Res 1994; 4 (3): 169-79
47. Crisostomo EA, Duncan PW, Propst M, et al. Evidence that
amphetamine with physical therapy promotes recovery of
motor function in stroke patients. Ann Neurol 1988; 23 (1):
94-7
48. Torok N. Old and new in Meniere disease. Laryngoscope 1977;
87 (11): 1870-7
49. Ruckenstein MJ, Rutka JA, Hawke M. The treatment of Me-
niere’s disease: Torok revisited. Laryngoscope 1991; 101 (2):
211-8
50. Fischer AJ. Histamine in the treatment of vertigo. Acta
Otolaryngol Suppl 1991; 479: 24-8
51. Kingma H, Bonink M, Meulenbroeks A, et al. Dose-dependent
effect of betahistine on the vestibulo-ocular reflex: a double-
blind, placebo controlled study in patients with paroxysmal
vertigo. Acta Otolaryngol 1997; 117 (5): 641-6
52. Botta L, Mira E, Valli S, et al. Effects of betahistine on vestib-
ular receptors of the frog. Acta Otolaryngol 1998; 118 (4):
519-23
53. Dziadziola JK, Laurikainen EL, Rachel JD, et al. Betahistine
increases vestibular blood flow. Otolaryngol Head Neck Surg
1999; 120 (3): 400-5
54. Colletti V. Medical treatment in Meniere’s disease: avoiding
vestibular neurectomy and facilitating postoperative compen-
sation. Acta Otolaryngol Suppl 2000; 544: 27-33
55. James AL, Burton MJ. Betahistine for Meniere’s disease or
syndrome [CD001873]. The Cochrane Database Systematic
Reviews. Available in the Cochrane Library [database on disk
and CD ROM]. The Cochrane Collaboration; issue 1. Oxford:
Oxford Update Software, 2001
56. Kanigel R. Why patients take Ginkgo. Hippocrates 1999 Oct:
11-3
57. Cesarani A, Meloni F, Alpini D, et al. Ginkgo biloba (EGb 761)
in the treatment of equilibrium disorders. Adv Ther 1998; 15
(5): 291-304
58. Weiser M, Strosser W, Klein P. Homeopathic vs conventional
treatment of vertigo: a randomized double-blind controlled
clinical study. Arch Otolaryngol Head Neck Surg 1998; 124
(8): 879-85
59. Shiller AD, Burke DT, Kim HJ, et al. Treatment with amantad-
ine potentiated motor learning in a patient with traumatic
brain injury of 15 years’ duration. Brain Inj 1999; 13 (9):
715-21
60. Brandt T. Vertigo: its multisensory syndromes. London:
Springer-Verlag, 1991: 17, 48-9
61. Brandt T. Benign paroxysmal positioning vertigo. Adv
Otorhinolaryngol 1999; 55: 169-94
© Adis International Limited. All rights reserved.
99
62. Brandt T, Daroff RB. Physical therapy for benign paroxysmal
positional vertigo. Arch Otolaryngol 1980; 106 (8): 484-5
63. Committee on Hearing and Equilibrium guidelines for the di-
agnosis and evaluation of therapy in Meniere’s disease:
American Academy of Otolaryngology – Head and Neck
Foundation, Inc. Otolaryngol Head Neck Surg 1995; 113:
181-5
64. Brandt T, Steddin S, Daroff RB. Therapy for benign paroxys-
mal positioning vertigo, revisited. Neurology 1994; 44 (5):
796-800
65. Shea Jr JJ. Classification of Meniere’s disease. Am J Otol 1993;
14 (3): 224-9
66. Bergenius J, Borg E. Audio-vestibular findings in patients with
vestibular neuritis. Acta Otolaryngol 1983; 96 (5-6): 389-95
67. Lacour M, Roll JP, Appaix M. Modifications and development
of spinal reflexes in the alert baboon (Papio papio) following
an unilateral vestibular neurotomy. Brain Res 1976; 113 (2):
255-69
68. Furman JM, Balaban CD, Pollack IF. Vestibular compensation
in a patient with a cerebellar infarction. Neurology 1997; 48
(4): 916-20
69. Barion U, Andretta M. Compensation mechanisms after acute
peripheral disorders of the labyrinth as a function of age. Acta
Otorhinolaryngol Belg 1988; 42 (1): 28-34
70. JC. Living without a balancing mechanism. N Engl J Med 1952;
246: 458-60
71. Hinojosa R, Nelson EG, Lerner SA, et al. Aminoglycoside oto-
toxicity: a human temporal bone study. Laryngoscope 2001;
111 (10): 1797-805
72. Minor LB. Gentamicin-induced bilateral vestibular hypofunc-
tion. JAMA 1998; 279 (7): 541-4
73. Oliveira J. Audiovestibular toxicity of drugs. Vol. II. Boca Ra-
ton (FL): CRC Press, 1989
74. Drachman DA, Hart CW. An approach to the dizzy patient.
Neurology 1972; 22 (4): 323-34
75. Bikhazi P, Jackson C, Ruckenstein MJ. Efficacy of antimigrain-
ous therapy in the treatment of migraine-associated dizziness.
Am J Otol 1997; 18 (3): 350-4
76. Diener HC, Kaube H, Limmroth V. A practical guide to the
management and prevention of migraine. Drugs 1998; 56 (5):
811-24
77. Diener HC, Limmroth V. Advances in pharmacological treat-
ment of migraine. Expert Opin Investig Drugs 2001; 10 (10):
1831-45
78. Vahedi K, Taupin P, Djomby R, et al. Efficacy and tolerability
of acetazolamide in migraine prophylaxis: a randomised
placebo-controlled trial. J Neurol 2002; 249 (2): 206-11
79. Juergens S. Alprazolam and diazepam: addiction potential. J
Subst Abuse Treat 1991; 8 (1-2): 43-51
80. Rice GP, Ebers GC. Ondansetron for intractable vertigo com-
plicating acute brainstem disorders. Lancet 1995; 345 (8958):
1182-3
81. Baloh RW, Winder A. Acetazolamide-responsive vestibulo-
cerebellar syndrome: clinical and oculographic features. Neu-
rology 1991; 41 (3): 429-33
82. Averbuch-Heller L, Tusa RJ, Fuhry L, et al. A double-blind
controlled study of gabapentin and baclofen as treatment for
acquired nystagmus. Ann Neurol 1997; 41 (6): 818-25
83. Lawden MC, Bronstein AM, Kennard C. Repetitive paroxys-
mal nystagmus and vertigo. Neurology 1995; 45 (2): 276-80
84. Afzelius LE, Henriksson NG, Wahlgren L. Vertigo and dizzi-
ness of functional origin. Laryngoscope 1980; 90 (4): 649-56
CNS Drugs 2003; 17 (2)
100
85. Spigset O. Adverse reactions of selective serotonin reuptake
inhibitors: reports from a spontaneous reporting system. Drug
Saf 1999; 20 (3): 277-87
86. Trindade E, Menon D, Topfer LA, et al. Adverse effects asso-
ciated with selective serotonin reuptake inhibitors and tricy-
clic antidepressants: a meta-analysis. CMAJ 1998; 159 (10):
1245-52
87. Kyle CJ, Petersen HE, Overo KF. Comparison of the tolerability
and efficacy of citalopram and amitriptyline in elderly de-
pressed patients treated in general practice. Depress Anxiety
1998; 8 (4): 147-53
88. Brauer HR, Nowicki PW, Catalano G, et al. Panic attacks asso-
ciated with citalopram. South Med J 2002; 95 (9): 1088-9
89. Ensrud KE, Blackwell TL, Mangione CM, et al. Central nervous
system-active medications and risk for falls in older women.
J Am Geriatr Soc 2002; 50 (10): 1629-37
© Adis International Limited. All rights reserved.
Hain & Uddin
90. Cumming RG. Epidemiology of medication-related falls and
fractures in the elderly. Drugs Aging 1998; 12 (1): 43-53
91. Herr RD, Zun L, Mathews JJ. A directed approach to the dizzy
patient. Ann Emerg Med 1989; 18 (6): 664-72
92. Sloane PD. Dizziness in primary care: results from the National
Ambulatory Medical Care Survey. J Fam Pract 1989; 29 (1):
33-8
Correspondence and offprints: Dr Timothy C. Hain, Depart-
ments of Neurology, Otolaryngology and Physical Therapy/
Human Movement Science, Northwestern University, 645
N. Michigan, Suite 1100, Chicago, IL 60611, USA.
E-mail: t-hain@northwestern.edu
CNS Drugs 2003; 17 (2)