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Drug treatment of vertigo in neurological disorders
Correspondence Address: Source of Support: None, Conflict of Interest: None DOI: 10.4103/0028-3886.170097
Vertigo is a common symptom in everyday clinical practice. The treatment depends on the specific etiology. Vertigo may be secondary to inner ear pathology, or any existing brainstem or cerebellar lesion but may also be psychogenic. Central vertigo is a consequence of a central nervous system lesion. It is often associated with a focal neurological deficit. Peripheral vertigo is secondary to dysfunction of the peripheral vestibular system and is usually characterized by an acute vertigo with loss of balance, sensation of spinning in the space or around self, and is exaggerated with changes of the head and body position; no other neurological deficit is present. Some medications may also cause vertigo. Depending on the cause of the vertigo, drugs with different mechanisms of action, physical therapy, psychotherapy, as well as surgery may be used to combat this disabling malady. Symptomatic treatment has a particularly important role, regardless of the etiology of vertigo. We reviewed the current medications recommended for patients with vertigo, their mechanisms of action and their most frequent side effects. Keywords: Central vertigo; peripheral vertigo; treatment
Vertigo is a common symptom that may be a manifestation of several underlying etiologies and may be caused by damage within the inner ear, by afflictions of the brain stem and cerebellum, or may even be psychogenic in origin.[1],[2] After headache, vertigo is the second most common symptom encountered in patients in neurological outpatient facilities around the world.[1] An acute onset vertigo with nausea and vomiting usually reflects damage to the vestibular system. Vertigo itself may either be of peripheral or central type.[2] The most frequent causes include vestibular neuritis, labyrinthitis, multiple sclerosis, or stroke in the region of the brainstem or cerebellum.[3] Central type vertigo is caused by lesions of the central nervous system, and is often associated with focal neurological deficits such as hemiparesis, hemisensory loss, speech disturbance, ataxia, or gaze palsy.[3],[4] Acute spontaneous vertigo that is associated with loss of balance, is accompanied by a sense of rotation of the surroundings or self, is worsened with the changing position of the head and body, with the absence of associated neurological deficits, is the main manifestation of peripheral vertigo, that occurs as a consequence of lesions of the peripheral vestibular system.[5] As many as 93% of patients with vertigo seen by a primary care physician suffer from benign paroxysmal positional vertigo (BPPV), acute vestibular neuritis, or Ménière's disease. The differences in the clinical presentation of both syndromes are shown in [Table 1]. The use of medications such as a select group of anticonvulsants, antidepressants, antihypertensives, diuretics, and barbiturates can also cause vertigo [6] Vestibular disorders can be treated, depending on their etiology, with medications, physical therapy, psychotherapy, or by surgical intervention.[2],[7]
Benign paroxysmal positional vertigo The benign paroxysmal positional vertigo (BPPV) occurs secondary to accumulation of calcium in the semicircular canals (canalithiasis).[8],[9] It is characterized by vertigo during sudden head movements, described by the patient, as the feeling of rotation of the surroundings. It most frequently develops in the morning, with changing position of the head while getting out of bed. Nausea and sometimes vomiting accompanies it for a few seconds up to 1 min. Occasionally, patients report the feeling of transient instability after the occurrence of vertigo. Examination reveals vertical-rotatory nystagmus, directed up or down, more pronounced on the side of the affected ear. The Dix- Hallpike' s maneuver, which provokes a characteristic nystagmus, is used to confirm the diagnosis.[10] BPPV usually resolves spontaneously within a few weeks. It is important to advise patients with BPPV to slowly get out of bed and avoid activities that require sudden movements of the head or looking up.[11] In patients with pronounced nausea and vomiting, metoclopramide 10 mg can be recommended via an intramuscular injection, intravenous bolus dose or within an intravenous infusion of normal saline. The drug can be repeated at every 6–8 h during the first 3 days. Another antiemetic drug that may be advised is promethazine 12.5–50 mg every 4–6 h.[12] This is a weak antipsychotic drug but a powerful sedative medicament with antiemetic and anticholinergic effects. The most common side effects of these drugs are due to their effect on dopamine receptors that may precipitate tardive dyskinesia and akathisia; or, their effect on cholinergic receptors that may cause a dry mouth, irritability, disorientation and constipation. Epileptic seizures and neuroleptic malignant syndrome are extremely rare side effects. The use of promethazine is not recommended for children younger than 6 years of age due to the risk of respiratory depression and sleep apnea, as well as in elderly patients, due to the anticholinergic effects of the medication.[13],[14] Significant relief in the symptoms precipitated by BPPV is achieved by applying the Epley maneuver, which is effective in 50–90% of patients.[8],[10] Other interventions, such as the Semont maneuver and positioning test for the horizontal semicircular canal may also be used.[1] These maneuvers should not be applied in patients with coexisting diseases of the neck and spine, significant carotid artery stenosis, or severe heart diseases.[9],[11] In patients, in whom these maneuvers are contraindicated, rehabilitation should initially be carried out under the strict supervision of a specialist, Subsequently, the patient's training in the use of self-applied exercises (Brandt - Daroff exercises) is recommended.[9] Vestibular neuritis Acute onset of vertigo, that is described by patients as an illusion of movement or a sense of rotation of objects surrounding the patient or the feeling of rotation of the patient himself in space, may be due to vestibular neuritis (neuronitis, labyrinthitis, neurolabirintitis or unilateral vestibulopathy).[1] The illness usually lasts for a few hours, days or weeks, followed by pronounced nausea, vomiting and gait instability. Most frequently, the disease is associated with herpes simplex virus type 1 which affects the vestibular ganglion and leads to loss of function of the vestibular labyrinth.[5] Neurological examination reveals horizontal nystagmus with a rotatory component, more pronounced on the side of the intact vestibular nerve. The neurological examination is normal. Romberg's test is positive, and the patient falls to the side of the lesion.[5],[15] Useful tests for the quick diagnosis of this disease are head shaking test, which directs the slow phase of the nystagmus to the damaged ear and its quick phase to the undamaged ear.[16] The Head Impulse Thrust Test shows that rapid eye-fixation movements are lost on the side of the damaged ear while saccades may be seen.[15] In addition to the usually occurring unilateral damage that produces the above mentioned manifestations, bilateral damage to the vestibular nerve may also occur, and is usually secondary to the effect of ototoxic drugs such as gentamicin. Bilateral damage may also be seen in cerebellar degeneration, meningitis, autoimmune disease, neuropathies, tumors, vestibular neuritis, and various otologic diseases.[17] Treatment of vestibular neuritis can be symptomatic and specific. The symptomatic therapy is directed towards the treatment of vertigo, nausea, and vomiting during the first 3 days, when the symptoms are most pronounced. With severe vomiting, parenteral therapy may need to be instituted [Table 2].
Antihistaminic drugs are preferred as they have sedative effects, as well as agonistic or antagonistic effects on H1, H2, H3 receptors, and act on the central components of the vestibular system.[13] The recommended dosage of chloropyramine is 20 mg. This medication may be repeated 2–3 times a day. Promethazine 25 mg may be administered intramuscularly every 6 h or may be given orally as tablets or syrup.[12] Meclizine tablets of 50 mg can be taken before the start of nausea, typically early in the morning, in one to two doses per day, and the dose can be repeated at 6 h intervals.[18] The most important side effect of this class of drugs is sedation which is most significant with promethazine. Patients should, therefore, be warned to avoid complex activities such as driving a motor vehicle while taking this medication.[19] Anticholinergics acting on muscarinic receptors such as scopolamine increase the patient's tolerance to movement and thus, play an important role in the treatment of vertigo.[13] Due of this effect, (they are often used to treat motion sickness (including sea-sickness, when they may be applied in the form of patches fixed over the ear. They are often used by divers also in this form. The side effects are rare, occurring in <1% of patients and are caused by anticholinergic effects of the medication. These include dry mouth, mydriasis, sweating disorder, tachycardia followed by bradycardia, urinary retention, and constipation.[14] Elderly patients may develop disorientation, confusion, and and even an hallucinatory syndrome with agitation. These drugs can provoke seizures and are contraindicated in patients with epilepsy. Hypersensitivity reactions are possible.[20] Their use is contraindicated in severe kidney or liver disease, prostatic hypertrophy, ileus, urinary retention, heart arrhythmia, and glaucoma. Their use is not recommended during pregnancy and lactation.[19] Benzodiazepines, in addition to their sedative effect, also inhibit the vestibular response by potentiating the action of gamma-aminobutyric acid. The recommended medications of this group are diazepam 10 mg parenterally or orally, which may be repeated every 6 h, lorazepam 1 mg intravenous or 2.5 mg as the oral dose, or clonazepam 0.5 mg intravenous or 2 mg in the form of tablets. The oral forms of these drugs may be given in patients with less pronounced vomiting. These are usually administered 2–3 times/day with a gradual increase of their dose.[14],[20] Due to their sedative effect, caution is needed in the elderly population. With intravenous administration, hypotension and respiratory depression may occur.[14],[19],[20] In cases of vestibular nerve neuritis, vitamin B is often administered since Vitamin B deficiency may lead to occurrence of nausea and vomiting (specifically due to vitamin B6 deficiency) and ringing in the ear (specifically due to vitamin B3, B6, and B12 deficiency). Vitamin B-complex may be given orally or as an intravenous infusion (the latter in cases with frequent vomiting) and may be repeated 2–3 times a day. They have no other short-term adverse effects with the exception of an occasional hypersensitivity reaction.[21] [Table 3] shows the specific treatment options to be used in cases suffering from vestibular neuritis.
Corticosteroids have an anti-inflammatory and antiedema effect. The use of methylprednisolone 100 mg daily in an intravenous infusion is recommended during the first 3 days of illness, with its dose tapering every 3rd day by 20 mg until the drug is stopped.[22] Prednisone may also be given either orally or as combined intravenous and oral therapy. Corticosteroids should always be used with gastro protective drugs and the patients potassium levels should be constantly monitored. Steroids are contraindicated in patients suffering from uncontrolled hypertension or diabetes mellitus, peptic ulcer, osteoporosis, infections, tuberculosis and hepatic dysfunction.[22],[23] Betahistine acts as an H1 receptor agonist (increasing the cochlear and cerebral circulation) as well as an H3 receptor antagonist (inhibiting the release of histamine and therefore, suppressing the function of the vestibular nuclei). It may be given orally, 2–3 times daily and its dose has to be titrated according to an individual patient. It is more effective at higher doses.[24] The most common side effects are headache and gastric disorders, and the drug is contraindicated in patients with a pheochromocytoma. Hypersensitivity reactions are also described. Its administration has to carefully monitored if the patient has bronchial asthma. It is not recommended for use in pregnancy and in lactating mothers, or in children.[25],[26] Calcium channel blockers such as flunarizine 5 mg orally administered once a day, or cinnarizine 75 mg orally administered 2–3 times/day, are recommended when antihistamines and antiemetics have had no effect. The effect of suppression of the vestibular responses is achieved using these drugs for a longer period of 6–8 weeks.[20] The most common side effects of this class of drugs are drowsiness (which endangers the performance of complex motor tasks such as driving a car) and also weight gain. Gastric disturbances and depression are less common. These drugs are not recommended during pregnancy.[19] In addition to the pharmacological treatment, psychotherapy and physical therapy may also be used in the treatment of chronic vertigo.[27] Ménière's disease This is a chronic disease characterized by intermittent episodes of vertigo that last for minutes or hours, and is associated with tinnitus and hearing loss. The disease can progress to deafness due to disorders of microcirculation in the labyrinth.[28] It is assumed that the cause of Ménière's disease is endolymphatic hydrops, but the pathogenesis is usually multifactorial, with the participation of immunological, metabolic, viral, traumatic, and allergic factors. A patient's genetic predisposition may also play a role. It can occur at any age but usually manifests between 40 and 60 years of age, and occurs more frequently in women.[28] The diagnosis is based on history, clinical presentation, neurological examination, and audiological tests. At the onset of the disease, the examination and investigation typically show hearing loss at low frequencies, and in the further course also at the high frequencies.[28] The same drugs used for the treatment of vestibular neuritis are administered [Table 2] and [Table 3]. In addition, beta-blockers and thiazide diuretics (to reduce fluid from the damaged ear) may be given. In Meniere's disease, vasodilators such as betahistine are used in much larger doses of up to 192 mg/day, and over a longer period of time that may extend to even a year.[29] Betahistine taken orally releases histamine, increases cochlear flow, and causes vasodilation in the stria vascularis, all of which help in reducing endolymphatic pressure.[26],[30] When medical therapy has no effect, surgical treatment should be considered. Patients are recommended bed rest and told to avoid movements. They are also asked to stop their alcohol and tobacco usage, and to bring about a modification in their diet (to avoid salt in order to reduce body's fluid retention).[31] Phobic postural vertigo The underlying pathological processes in this condition are different mental disorders, depression, and anxiety. According to some data, phobic postural vertigo is the second most common diagnosis in a patient with vertigo.[32] Patients often complain of postural vertigo, which they describe as dizziness and postural sway, drift or gait instability. All of these manifestations increase or decrease in different provocative situations. The affected persons often fall, and this symptom is usually manifested in front of other people. A patient with an obsessive-compulsive personality and a tendency towards introspection, or a depressed patient, is prone to this condition.[32] Neurological examination is always normal. In 25% of patients with phobic vertigo, a well-defined vestibular disorder actually precedes this condition.[32] After detailed diagnostic tests have ruled out other causes of vertigo, physicians should explain to the patient that no organic disease has been found; treatment is then directed at addressing the patient's fear. Psychoeducational therapy and an interview with a psychologist or psychiatrist usually leads to good results.[33] If pharmacoherapy is needed for depression, selective serotonin reuptake inhibitors are recommended, which are administered once a day, in the morning These include fluoxetine 20 mg, paroxetine 10 mg, sertraline 50 mg or tricyclic antidepressants, such as imipramine 25 mg divided into three daily doses or amitriptyline 10 mg (at bed time). The side effects of this class of drugs are anxiety, insomnia, gastrointestinal disturbances, decreased libido, and sexual dysfunction. The use of paroxetine is not recommended during pregnancy because of its teratogenic potential.[19] A potentially life-threatening serotonin syndrome, secondary to excess of serotonin in the body can occur while this class of drugs is being given. The risk is increased when a new combination of medications is administered, both of which affect serotonin levels. It may also occur when the dosage of an existing drug affecting serotonin levels is additionally increased. Therefore, monoamine oxidase inhibitors or triptans should not be used with selective serotonin reuptake inhibitors. It is advisable to avoid food material containing tyramine, for example, aged cheese or red wine. However, the side effects are rare and significantly less pronounced than encountered when tricyclic antidepressants are used. Tricyclic antidepressants may cause drowsiness or insomnia, tremors, antimuscarinic effects such as blurred vision, constipation and urinary retention, hypotension and cardiac arrhythmia, disorientation, and seizures. These medications often lead to weight gain and sexual dysfunction.[14] Tricyclic antidepressant therapy should be started in a low dose, especially in elderly patients, and the doses should be stepped up gradually.[14],[19] For the treatment of anxiety, benzodiazepines are recommended. These include diazepam, bromazepam and lorazepam administered orally in low doses 2 to 3 times a day [Table 4].[19],[20]
The most common causes of central vertigo are stroke in the region of the brainstem or cerebellum, migraine, multiple sclerosis, and vestibular nerve tumors.[34],[35],[36] Vertigo has been reported within the clinical spectrum of migraine attack and is treated according to the standard principles of treatment of an acute migrainous attack. It can also occur as a side effect of drugs administered for the management of acute migraine. These drugs include triptans, as well as drugs used in the prophylactic therapy of migraine, such as beta-blockers or calcium channel blockers.[2],[37] The treatment depends on the underlying disease [Table 5].
In the case of stroke, standard acute stroke management with measures for the secondary prevention of stroke are instituted.[4] If vertigo occurs as a symptom of a stroke, other symptomatic drugs with differng mechanisms of action could be used [Table 2] and [Table 3]. In the case of multiple sclerosis, standard therapeutic principles are applied.[14] Besides vestibular nerve tumors, vertigo can also be due to arachnoidal cysts in the posterior fossa or Arnold- Chiari malformation More Details More Details; in these cases, besides symptomatic therapy, surgical intervention may also be considered. In rare cases of episodic ataxia type 2, caused by an autosomal dominant mutation in the CACNA1A gene resulting in the dysfunction of voltage-dependent calcium channels, the use of 4-aminopyridine (potassium channel blocker) and acetazolamide is recommended.[38] The side effects of both these drugs are distal paresthesias; aminopyridine can predispose to epileptic seizures and arrhythmia, while acetazolamide can be associated with changes in taste as well as nausea, vomiting, diarrhea, polyuria, and drowsiness or confusion (the latter due due to dehydration). The use of acetazolamide may precipitate the development of renal calculi so patients should be advised to drink plenty of fluids while being on this medication.[38],[39] For patients with central vertigo of vascular etiology, especially in the geriatric population, the use of nicergoline, a derivative of ergot alkaloids can be recommended.[40] This drug is a potent, selective antagonist of the alpha-1A adrenergic receptors with a primary effect of raising blood flow by its vasodilatory mechanism.[41] The drug also inhibits platelet aggregation, increases the cholinergic and catecholaminergic transmission and has neurotrophic and antioxidant properties.[42] The recommended doses are 5–10 mg, 3 times a day. The side effects include nausea, hot flushes, mild gastric disturbances, and hypotension. High doses of the drug can cause bradycardia, increased appetite, agitation, diarrhea, and sweating. The drug is not recommended during pregnancy. It is also contraindicated in porphyria. Rare but important complications of ergot derivatives are fibrosis and ergotism. It is necessary to avoid its concomitant use with propranolol whose cardiodepressive effects are potentiated. Caution is also needed if this drug is combined with other vasodilators.[14],[42] For patients with chronic vertigo, vestibular rehabilitation is also recommended.[27]
Vertigo is a common complaint in everyday clinical practice. The causes of vertigo are numerous and treatment depends on the underlying etiology. Drugs with different mechanisms of action, physical therapy, psychotherapy, and in some cases, surgical intervention may be administered. Symptomatic treatment has a special role in the amelioration of vertigo regardless of its etiology. While administering medications for the treatment of vertigo, it is important to understand their mechanisms of action and side effects. Acknowledgment This work was supported by the project of the Ministry of Science of Serbia No. 175022. Financial support and sponsorship This work was supported by the project of the Ministry of Science of Serbia. Conflicts of interest There are no conflicts of interest.
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]
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