VESTIBULAR SEDATIVE DRUGS- reducing misuse why and how ........Dr. Anirban Biswas,
Vertigo & Deafness Clinic,
BJ-252, Salt Lake, Sector-2,
All pictures presented in this article have been downloaded from different sites in the internet through Google Images.The reader may find the source by searching the caption of each figure in Google Images.
Table of Contents
VESTIBULAR SEDATIVE DRUGS- reducing misuse why and how
Disorders of the balance system affect a very large part of the population. Patients suffering from balance disorders present with head spinning, dizziness, imbalance, unsteadiness and associated symptoms. The overall incidence of balance disorders is 5-7% of the population and is as high as 35% in patients older than 40 years (1) and about 70% in patients above 65 yrs of age (2). International statistics report that 5-10% of the population presents to the doctor with vertigo / imbalance as a new case every year. The incidence of falls is 25% in subjects older than 65 years (1). Prevalence of balance disorders or dizziness is 15.8% of the population according to a study of Wiltink, J., R. Tschan, et al. (2009)(3).65% of individuals (older than 60 years of age) experience dizziness or loss of balance; often on a daily basis (4)(5). Indian statistics are not available but averages of published studies of prevalence of vertigo in different countries shows that 15% of the general population suffer from balance disorders.
Balance disorders are hence a very common disease that affects a very large part of the population. This makes the business potentiality of any drug that can be claimed to be helpful in balance disorders very attractive for commercial exploitation. In a one year span (October 2015 to Oct 2016) the sale of anti-vertigo drugs (comprising of just cinnarizine, flunarizine, betahsitine, and the cinnarizine+dimenhydrinate combination) in India was of about Rs 421.5 crores. There are other popular anti-vertigo drugs also like prochlorperazine and meclizine which if added would take the figure to above Rs.500 crores. In the month of October 2016 alone 757.7 lakh units of anti-vertigo medicines were sold.
Balance disorders are a subjective disorder that causes physical, functional and psychological impairment and a social embarrassment that is not compatible with normal life. It imposes severe restrictions on the patient and also induces psychological disorders like anxiety, apprehension, insecurity and depression. Most balance disorder patients have a very poor quality of life with restricted mobility, persistent fear of losing balance or of falling down and a constant apprehension of impending vertigo. In addition to their physical impairment they are also mentally distressed. Hence patients suffering from balance disorders are a harried lot who would lurch at any opportunity for relief. This makes them easy target for any commercial endeavour. The enormity of the market for drugs than can be sold for the treatment of vertigo and / or balance disorders and the gullible patient’s hankering for trying out anything that promises relief from vertigo is therefore very luring to pharmaceutical companies. No wonder commercial interests overrule ethical and scientific therapeutic principles and influence the treatment of balance disorders. This is harmful to the interest of the patient. Pharmaceutical companies use all marketing means, if not gimmicks to promote the sale of such drugs paying scant attention to medical principles. This happens primarily because there are no restrictions on sale of these drugs (all these are available over the counter and are sold even without valid medical prescriptions) and because of the huge profit margins involved in the sale of these drugs. There is unethical, illogical and unscientific promotion of such medicines and even false propaganda leading to over-prescription and over-use. Vertigo and imbalance are such scary conditions for the patient that often patients are scared to stop the medicines and go on using them by purchasing the anti-vertigo medicines from medicine counters even after the patient is symptom free and is not having the vertigo or any imbalance. The medicines are erroneously used as a prophylaxis against vertigo/ imbalance which is medically wrong, scientifically irrational and logically untenable if not blatantly harmful. Even some naive medical practitioners prescribe these anti-vertigo medications prophylactically being fed with incorrect and biased information by the pharmaceutical companies. All the anti-vertigo medications are at best symptom relieving drugs and have no prophylactic or therapeutic role whatsoever. The loser in the deal is always the patient while all other stake holders profit from it.The outcome of this is dangerous as unnecessary long continued use of these drugs is detrimental to health of the patient. Use of these drugs beyond a specified period and beyond requirement actually damages the balance system and delays if not prevents the restoration of normal balance function some references of which are cited below. Most drugs used for management of balance disorders have serious side effects some of which is permanent. It is medically established that overuse of most of these drugs can completely jeopardise the natural process of restoration of balance (after the balance system has been damaged by disease). The process of restoration of balance after the balance organs have been damaged is a natural process called vestibular compensation and this is inhibited by most of the anti-vertigo medications. If the compensatory mechanism is jeopardised, the patient remains imbalanced and the normal balance function is not restored. Any imbalance is physically restrictive and mentally traumatic for the patient. Balance disorders induce psychological distress; balance disorders and psychological disorders are comorbid conditions and one perpetuates the other. Since balance disorders are so very common involving so many patients and since the impact on quality of life caused by balance disorders is so very severe, it is high time that an analysis and auditing of the management of balance disorders is undertaken. Nearly all drugs sold in the market that claim to cure balance disorders are OTC (over the counter) products and most do not come under any price restriction which is prevalent for many other drugs like antibiotics, anti diabetics , anti hypertensive and anti cancer drugs. Hence free sale of these are allowed and even a valid medical prescription is not mandated for the sale of these potentially dangerous and harmful drugs. The purpose of this document is to have an in-depth appraisal of the current scenario of management of balance disorders and offer solutions for corrective measures if not to make an attempt to stem the rot and thereby protect the hapless balance disorder patient from falling prey to the unscrupulous propaganda for anti-vertigo drugs . This is necessary since the currently prevalent practice of management of balance disorders esp pharmacotherapy appears unethical, injudicious, flawed and driven primarily by commercial considerations all of which are health-wise damaging and detrimental to the unfortunate balance disorder patients. This document not only highlights the ill effects of the anti vertigo drugs but advocates against overuse and unrestricted sale.
The balance system is very complex and involves multiple organs and multiple systems of the human body; the vestibular labyrinth in the inner ear is one of them. Though the vestibular causes of imbalance are less than 50% (6) yet the drugs used to sedate the vestibular labyrinth are indiscriminately used in patients complaining of any of the symptoms like head spinning (vertigo), dizziness, light-headedness, unsteadiness, blackouts etc. without even ascertaining whether the vestibular labyrinth is really malfunctioning or whether sedating the vestibular labyrinths is actually necessary or not. The drugs used to sedate the vestibular labyrinth are called vestibular sedatives or anti-vertigo drugs.These drugs do much more harm than benefit and are capable of only providing temporary relief from the symptom of acute vertigo or head spinning. Serious adverse effects of these drugs can range from Parkinsonism (7) to even life threatening Neuroleptic Malignant syndrome(8) .The biggest drawback is that these drugs jeopardise the natural process by which the normal balance function is restored after it has been damaged by disease. The vestibular labyrinths are made of special sensory epithelium that detect movement very much like the retina in the eyes that detects light and is responsible for our vision and the cochlea in the ear that detects sound and is responsible for our hearing. All special sensory epithelium cells are made of cells that are non-mitotic and once damaged are damaged for life i.e., they do not regenerate. The anti-vertigo drugs or for that matter any medicine cannot regenerate the cells of the vestibular labyrinth if dead. The purpose of the anti vertigo drugs is just to provide symptomatic relief from any rotating / spinning sensation if there is any and that too only temporarily even though they are unscrupulously touted by the pharmaceutical companies as the panacea for all diseases that manifest as vertigo or imbalance. The anti-vertigo drugs are vestibular suppressants and suppress the sensitivity and functioning of the vestibular labyrinth. If there is no spinning sensation i.e., if the feeling is that of instability / dizziness/ blackouts / sinking anti-vertigo drugs have no role whatsoever. The head spinning i,e. the spinning / rotatory sensation felt by the patient which is called true vertigo or even the related sensations like instability dizziness, sinking sensation are just the manifestation of some underlying disease and are not a disease in itself. The doctor’s job is to ascertain / diagnose the cause of the vertigo and the other symptoms and treat the underlying disease instead of camouflaging / suppressing the symptom of vertigo.
Most of the vestibular disorders that cause vertigo /imbalance have specific therapies which do not require treatment with the vestibular sedative (or anti-vertigo) drugs. The mainstay of treatment remains vestibular rehabilitation and specific treatment directed to the disease that is causing the vertigo /imbalance. The vestibular compensation mechanism which helps a balance disorder person to recover and get back the normal balance function is also hampered by these drugs and long term use of such drugs leads to a permanent instability which cannot be cured by any means. Some of these drugs which are available as OTC products in our country with all chemists are actually not approved by Food and Drug Adminstration (FDA) of USA. Other developed countries also have strict regulations for these drugs.
These drugs do have a limited role in relieving the symptom of head spinning but only in the acute stages of the disease and should not be used for more than 3-5 days (9)(10)(11)(12). Use of these merely symptom relieving drugs for vertigo camouflages the underlying disease which remains undiagnosed, induces a false sense of complacency both in the patient and on the doctor and what is worst is that it also jeopardises the natural process of restoration of balance. This policy paper is presented to highlight this particular aspect and to recommend enlisting these drugs in schedule H so that they cannot be sold without valid medical prescriptions and also to bring all these drugs under price bar so that the profitability is reduced. The later will ensure that the over hyped advertisement and mindless promotion among doctors for the anti-vertigo drugs by the pharmaceutical companies which is sending wrong signals to all stake-holders is reduced.
Vestibular compensation is a unique corrective mechanism ingrained in the human biological system wherein there is reorganization of internal connections of the brain which helps in maintaining the balance in spite of a lesion in the vestibular labyrinth. But for this to occur, brain needs inputs from the vestibular labyrinths in the form of vertigo.
For vestibular compensation to occur sensory input in the form of vertigo is of utmost importance. This helps brain to understand that there is difference in sensitivity of both labyrinths (termed as ‘sensory conflict’ in medical parlance) and that one of them is hypo-functioning or working at suboptimal levels; hence the internal connections are reorganised and recalibrated accordingly. More the sensory conflict, more is the vertigo and better is the compensation (9)(10).
Any drug which reduces the sensory conflict by reducing the feeling of vertigo hampers the process of compensation. There is no drug with adequate and convincing evidence to claim that it helps i.e., enhances / expedites the process of compensation (9) (Figure 1). On the other hand it is known that any drug that depresses the central nervous system (CNS) jeopardises vestibular compensation. Most drugs that are used for supressing vertigo actually depresses the CNS except for betahistine which is not a CNS depressant. But as it reduces the symptom of vertigo it definitely reduces the sensory conflict and hence also inhibits vestibular compensation though may be at a lesser level than the other anti-vertigo drugs all of which depresses the CNS. The compensatory mechanism in the brain is most active in the first few days after a vestibular assault, hence one has to be very discerning in supressing vertigo with the anti vertigo drugs when there is an acute damage to the vestibular labyrinth.
Objectives for medical treatments of vertigo are as follows (9):
Following are the commonly used drugs in the treatment of vertigo.
-Prochlorperazine - Cinnarizine
- Meclizine - Diazepam
All of these drugs are discussed in details in the following pages, but there are few common points to all of these drugs. Prochlorperazine, cinnarizine, dimenhydrinate and meclizine are antihistaminic anti cholinergic drugs and hence share the same effects and adverse effects with minor variations. Betahistine is a histamine analogue and acts differently but no doubt has a anti vertigo effect.
Michel Lacour has mentioned in 2006 scientific paper (figure 2), that following a sudden unilateral vestibular loss, patients exhibit incapacitating symptoms, such as nausea, vomiting and vertigo. These symptoms can be stopped or limited using vestibular suppressive drugs. However, as the literature suggests that drugs with sedative effects slow down the recovery process, it is therefore recommended that these agents are prescribed for a limited period of time, and that the use is restricted to the first 3 or 4 days after an acute vestibular loss.(13)(9)
Baloh R was mentioned in Vestibular Rehabilitation book that drugs exerting sedative effect on Vestibular system should be used only first 24hrs (11)(12)(Figure 3).
Mukherjee et al mentioned in in an article on vertigo and dizziness (Figure 4) that- Vestibular suppressants should be prescribed over a limited period of time following an acute vestibular lesion. Chronic use is not advocated as it probably retards the process of central vestibular compensation. A process of rehabilitation should be started after the acute phase and this includes vestibular rehabilitative exercise. Vestibular suppressants and other central depressant medicine should be discontinued as both can interfere with the adaptive plasticity considered the basis for successful rehabilitation. (14)
These drugs are commonly used in patients of vertigo. They are often misused and are also available over the counter (OTC). We are discussing over here the mechanism of action and harmful effects of these drugs on individual basis.
Belongs to the phenothiazine group of antipsychotics.. Antipsychotic drugs are tranquilisers that are used to treat serious mental disorders like schizophrenia, bipolar disorders, depression, mania, hallucinations, delusions and similar mental states. Though it is used to treat dizziness it itself may induce dizziness and vomiting in addition to, drowsiness restlessness., constipation, and dry mouth in patients when prescribed as these are the common side effects of all antipsychotic drugs. Though prochlorperazine offers very good symptomatic relief in acute vertigo yet, it is an antipsychotic drug meant for serious mental disorders with many untoward effects and so should be used with utmost caution.
Prochlorperazine has following pharmacological effects-
Following are the possible adverse effects of prochlorperazine
Figure 5 Oculogyric Crisis
Figure 14 Neuroleptic Malignant Syndrome(15)
Has following mechanisms of action
It provides a good symptomatic relief to the patient but its side effects outweigh the benefits and hence this drug is best avoided more so because we have other alternatives.
Following is the list of adverse effects of cinnarizine
The anticholinergic effect induces CNS depression and drowsiness by virtue of which the vestibular compensatory mechanism is inhibited
Figure 22 Drowsiness
Best used for symptomatic relief and hence use like for all other anti vertigo drugs should be limited to a maximum of 3-5 days or as soon as the symptom is relieved whichever is earlier. Competitively antagonizes the actions of histamine at H1 receptors. Its main advantage is that the anticholinergic effects are lesser compared to other conventional antihistaminic antivertigo drugs like prochlorpearzine, cinnarizine and dimenhydrinate. It is approved as OTC product by FDA hence safety profile is comparatively much better than the other anti vertigo drugs
Adverse effects of meclizine are due to both anticholinergic and antihistaminic properties which have been elaborated earlier but the effects are much milder in nature.
It is a anti-vertigo drug without any CNS depressive effects. It provides symptomatic relief in vertigo by its action on some histaminergic receptors in the higher vestibular pathways. It has been shown to be effective in the treatment of Meniere’s disease which is one of the not so common causes of vertigo.
Adverse Effects of Betahistine
It is a very good anxiolytic and has a CNS depressive effect and by this provides symptomatic relief in acute vertigo. As it is a CNF depressant just one or two doses to control symptoms in very acute stage is the most that is allowable. It has tranquilising & anxiolytic effects. Since it decreases resting activity of vestibular nuclei ; hence provides symptomatic relief. It acts upon the reticular formation and limbic systems in the brain hence reduces concomitant anxietyBut as it is a CNS depressant it should best be totally avoided.
Apart from the above drugs which are basically symptom relieving medicines, pharmacological treatment of vertigo should be directed towards treating the underlying disease causing the vertigo after identifying it. Treatment includes drugs for migraine prophylaxis, diuretics, anti epileptics, steroids, anti-virals, antibiotics, SSRIs, benzodiazepines, nootropic agents, anti-oxidants etc.
Various types of physical therapy especially excercises like Cawthorne Cooksey Excercises; Yogic Asanas; Tai Chi excercises are recommended for vestibular rehabilitation and promoting of vestibular compensation. Depending on which part of vestibular labyrinth is involved specific exercises are available and many more are being developed helping the person to lead a normal life. For disorders like positional vertigo, the different liberatory manoeuvres work wonders. The commonest cause of vertigo in any clinic that can diagnose the cause of the vertigo is a disorder called Benign Paroxysmal Positional Vertigo (BPPV) for which there is no medical cure and can be corrected by different physical therapies called liberatory manoeuvres then and there in the clinic itself. In spite of this, patients of BPPV are prescribed medicines for prolonged periods which they continue even after the BPPV gets corrected by itself. BPPV like some other causes of vertigo is a self limiting condition that is corrected in a few days without any treatment
This is the most important aspect of treatment as the patient needs to be reassured about his condition and also to overcome his apprehension and anxiety. Very often some psychological impairment co-exists which requires counselling.
The relevant authorities like drug controllers and health care regulatory bodies should take steps to:-
1) Bring all anti-vertigo medicines under a fixed price bar so that the profitability is reduced.
2) Make wrong propaganda and irrational promotion of medicines by pharmaceutical companies a punishable offence
3) Introduce auditing of prescriptions so that medicines and the dosage prescribed by doctors is medically justifiable at least for the anti-vertigo drugs. A suitable legislation will be a effective deterrent for irrational prescriptions.
4) Bring all anti-vertigo drugs under schedule H, so that these drugs cannot be sold without a valid medical prescription.
Vertigo and imbalance are very common disorders which not only cause a severe physical morbidity and also have a psychological impact both of which together bring about a poor quality of life in the patient. However both vertigo and imbalance are not a disease in themselves. Like fever and pain, vertigo / imbalance is just a symptom or manifestation of an underlying causative disorder. This underlying cause needs to be diagnosed and treated. Unfortunately, the current trend in medical practice is to treat vertigo and imbalance by symptom relieving anti-vertigo drugs which camouflage the underlying disorder without in any way curing the causative pathology. This happens primarily because of the hype in promotion of the anti-vertigo drugs which are touted by different pharmacological companies selling them as the panacea for vertigo and imbalance irrespective of the cause. The pharmaceutical companies promote the long continued use of the anti vertigo drugs using different marketing gimmicks and use different tricks of disinformation and misinformation to convince doctors on the curative effects of the anti vertigo drugs. Their professional marketing strategies easily dupe naive doctors into towing their line. This results in over-prescription and irrational use of the anti-vertigo drugs. The price for this in terms of health and money is paid by the hapless patient. All the anti-vertigo drugs have very serious side effects and even prevent the proper development of a natural corrective process called ‘vestibular compensation’ ingrained in our systems which actually restores balance after the balance organs have been damaged by disease. If the vestibular compensation does not take place as desired, the patient remains imbalanced which has a serious impact on the physical and mental wellbeing of the patient. Persistent vertigo and imbalance causes a sense of insecurity, fear and other psychological disorders like mental depression and anxiety. These psychological conditions further augment the imbalance and starts a vicious cycle where one perpetuates the other. The current consensus among neurotologists (medical specialists who specialise in the treatment of vertigo/ imbalance) is that anti-vertigo drugs should never be used for more than 3-5 days. In fact some authorities recommend that they should not be used for more than 24 hours. But the scenario in medical practice is completely different and doctors are found to prescribe these drugs for weeks and months together and what is worse is that patients then go on taking these drugs by purchasing them over the counter for years at a stretch. The impact of this on the balance system is very bad and most such patients develop a permanent instability and consequently a very poor quality of life more so because of the induced psychological impact caused by the balance disorder. What was once a correctable / controllable medical disorder now becomes unmanageable and the patient becomes a wreck more mentally than physically because of the persistent imbalance induced by the irrational and unscientific therapy which is totally against medical consensus. The underlying disease remains undiagnosed and progresses unabated. This is a real menace and drastic steps, if not ‘surgical strikes’ need to be taken immediately to stop this illogical and harmful practice of prolonged use of anti-vertigo drugs. Some recommendations are presented in the document.
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