3 vertin clinical trials
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3 vertin clinical trials
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3 vertin clinical trials
- 2. 2 Effect of Betahistine on cochlear blood flow Effect of I. V. Betahistine on diameter of anterior inferior cerebellar artery and cochlear blood flow studied in guinea pigs using Laser Doppler Flowmetry Laurikainen, Eur Arch Otorhinolaryngol, 1998, 255, 119-123
- 3. 3 Mean increase of 40% in cochlear blood flow with infusion of Betahistine 90 100 110 120 130 140 150 0 0.5 1 1.5 2 2.5 3 3.5 4 Time (min after infusion) %changefrombaselinein CBF Laurikainen E, Eur Arch Otorhinolaryngol, 1998, 255, 119-123
- 4. 4 Effect of Betahistine on Cochlear blood flow Mean increase of 40% in cochlear blood flow (CBF) with Betahistine Diameter of Anterior Inferior Cerebellar Artery (AICA) increased by 17-20% indicating that Betahistine evoked increases in CBF resulted primarily from vasodilation of AICA Laurikainen E, Eur Arch Otorhinolaryngol, 1998, 255, 119-123
- 5. 5 Effect of Betahistine on Cerebral Blood Flow 50 adult patients with Vertebrobasilar arterial insufficiency with dementia. 2 treatment periods of 6 weeks each. Group I Betahistine 8 mg q.i.d.followed by placebo Group II Reverse order Assessment : Neurologic, Neuropsychologic, cerebral blood flow -- Rivera V M et al, J. Am. Geriatr. Soc, (1974), 22/9, 397-406
- 6. 6 Mean increase of 14. 8 % in cerebral blood flow with Betahistine Betahistine -2.60% + 14.80% -4% 0% 4% 8% 12% 16% Placebo %changeinmean regionalcerebralbloodflow Adapted from Rivera VM et al, J.Am. Geriatr.Soc., (1974), 22/9, 397-406
- 7. 7 020406080100 0 5 10 15 20 Time(Min) after Betahistine administration %spikenumber 0.1mg/kgBH 1mg/kgBH 5mg/kgBH Dose-dependent reduction in spike no. of polysynaptic neurons in Lateral Vestibular Nucleus (LVN) with Betahistine Unemoto et al, Arch Otorhinolaryngol, 1982, 236, 229-236
- 8. 8 Conclusion Spike generation of polysynaptic neurons in Lateral Vestibular Nucleus (LVN) is inhibited by intravenous as well as iontophoretic administration of Betahistine in a dose-dependent manner. Unemoto et al, Arch Otorhinolaryngol, 1982, 236, 229-236
- 10. 10 1.8 2.2 2.6 3 3.4 3.8 0 5 10 crossover weeks MeanFrequencyScore Significant reduction in frequency of vertigo attacks with Betahistine compared to placebo-Prophylactic effect --Oosterveld W J et al, J Drug Ther. & Res. (1989), 14 (4),122-6 Betahistine Placebo
- 11. 11 0.4 0.6 0.8 1 1.2 1.4 0 5 10 crossover weeks Meanseverityscore Significant reduction in severity of vertigo attacks with Betahistine compared to placebo-symptomatic relief --Oosterveld W J et al, J.Drug Ther. Res., (1989), 14(4), 122-6 Betahistine Placebo
- 12. 12 0 1 2 3 4 5 0 30 60 90 days intensityofattacks Significant reduction in intensity of Vertigo attacks with Betahistine Betahistine Placebo -- Legent F et al, Concours Med, (1988), 29 (Examination Time)
- 13. 13 0 5 10 15 20 25 0 30 60 90 days No.ofpatientsfreeofVertiginous attacks -- Legent F et al, Concours Med, (1988), 29 No vertigo attacks in 75% of patients after 3 months of the treatment with Betahistine Betahistine Placebo (Examination Time)
- 14. 14 Improvement of 28 patients with Meniere's disease treated by Betahistine 16 11 1 0 2 4 6 8 10 12 14 16 18 Complete relief Partial relief No response Hicks, Arch Otolaryngol, 1967, 86, 610-3 Numberofpatients
- 15. 15 ADDITIONAL USEFUL FEATURES OF BETAHISTINE Dose-dependent effect Facilitates vestibular compensation
- 16. 16 Dose-Dependent effect of Betahistine in Improving cochlear blood flow (Laurikainen, 1993) Reducing firing frequency of vestibular nuclei (Unemoto, 1982 ) Reducing duration of nystagmus (Oosterveld, 1987) Reduction in resting firing of ampullar receptors (Botta, 2000) Higher the dose, faster and better the effect
- 17. 17 Betahistine - Dose-Dependent Effect on Induced Vestibular Nystagmus 3 different single oral dosages of Betahistine (8, 16, 32 mg) to 10 normal subjects with inter test interval of 1 week Assessment : Duration of induced nystagmus Post-treatment duration calculated as % of pre- treatment duration. --Oosterveld W J, Clin Otolaryngol, (1987), 12, 131-5
- 18. 18 20 40 60 80 100 0 1 2 3 4 5 6 7 8 Hours after drug intake --> Nystagmusduration% 8 mg 16mg 32 mg --Oosterveld W J, Clin Otolaryngol, (1987), 12, 131-5 Betahistine: Dose-dependent reduction in duration of induced nystagmus
- 20. 20 115.6 72.2 70.4 113 73.2 72 0 100 B.P. systolic B.P. diastolic pulse pre-treatment post-treatment No changes in B. P. & pulse after treatment with Betahistine in Normal Subjects Adapted from : --Stough AR, Curr. Ther. Res., 1963, 5, 10, 542-9
- 21. 21 Tolerance of Betahistine No drowsiness No gastric side effects No cardiac side-effects Bradoo et al, Ind. J. Otolaryngol H N S, 2000, 52(2), 151-8, Betahistine IN Collin Dollery Therapeutc drugs B 62-5
- 23. 23 Results: Comparing efficacy of Betahistine and Cinnarizine in facilitating vestibular compensation Lesser Vestibulo Ocular Reflux (VOR) asymmetry score with Betahistine treatment than with Cinnarizine treatment Higher degree of vestibular compensation with Betahistine than with Cinnarizine Faster recovery with Betahistine than Cinnarizine Colletti, Acta Otolaryngol, 2000, suppl 544, 27-33
- 24. 24 Effects of Betahistine metabolite on firing activity of frog ampullar receptors assessed Nerve firing rate recorded from ampullar nerve both in resting & mechanically evoked state 3 Betahistine metabolites administered (10-7 M to 10-2 M ) M1 (aminoethylpyridine), M2 (Hydroxyethyl pyridine), M3 (pyridylacetic acid) --Botta L, Acta Otolaryngol, 2000, 120, 25-7
- 25. 25 Results Only one metabolite M1 (Aminoethyl pyridine) had significant effects on ampullar firing rate. Two other metabolite M2 and M3 were completely inactive M1 (Aminoethyl pyridine) reduced resting ampullar firing rate, mechanically evoked responses unaffected. --Botta L, Acta Otolaryngol, 2000, 120, 25-7
- 26. 26 % changes in firing activity of ampullar receptors Concentration (M) of Betahistine metabolite -Botta L, Acta Otolaryngol, 2000, 120, 25-27 100 100 95 78 100 85 18 0 0 20 40 60 80 100 120 Cont 10(-6) 10 (-4) 10(-2)% Evoked Resting % firing
- 27. 27 Conclusion Betahistine metabolite (Aminoethyl pyridine) reduces the resting discharge / ampullar firing, without affecting the evoked responses Hypothesis put forward -- Antivertigo action of Betahistine is first achieved by Betahistine itself and then sustained by the metabolite-aminoethyl pyridine - Botta L, Acta Otolaryngol, 2000, 120, 25-27
- 28. 28 Management of acute vertigo with Betahistine Dr. R.A. Bradoo Head, Dept. of ENT , Lokmanya Tilak Municipal Medical College and Hospital, Sion, Mumbai Ind. J. Otolaryngol Head Neck Surgery April - June 2000, 52(2), 151-8
- 29. 29 An Open study Methodology 29 patients with at least one episode of vertigo in the preceding month Treatment period maximum of 6 weeks or earlier until remission of attacks Betahistine at a dose of 16 mg.t.i.d. Bradoo RA, Ind. J. Otolaryngol H N S, 2000, 52 (2), 151-8
- 30. 30 Weekly Assessment upto 6 weeks Frequency - number of attacks per week Duration of vertigo attacks in minutes Severity of attacks as No attacks 0 Absent No attacks interfering with routine 1 Mild some interference with routine 2 Severe disruption of daily routine 3 Incapacitating Confined to bed 4 # Effect on associated symptoms such as tinnitus, hearing loss, nausea, vomiting, faintness, headache Bradoo RA, Ind. J. Otolaryngol H N S, 2000, 52 (2), 151-8
- 31. 31 At the end of the treatment Global Evaluation Patients’ & Investigators’opinion on efficacy & tolerance of the treatment Tolerance of the treatment Side effects observed if any Any gastrointestinal disturbances Questions on experience of drowsiness and effect of drug on the quality of life Bradoo RA, Ind. J. Otolaryngol H N S, 2000, 52 (2), 151-8
- 32. 32 Mean symptom score before & after treatment with Betahistine 16 mg t.i.d. (n=29) Bradoo RA, Ind. J. Otolaryngol H N S, 2000, 52 (2), 151-8 Parameter Weeks of Betahistine treatment 0 1 2 3 4 5 Frequency 14.66 5.62* 3.9** 0.69** 0.41** 0** 100% 38.3% 26.6% 4.7% 2.85 0% Duration 33.81 15.8* 6.4** 2.07** 1.04** 0** (min) 100% 46.8% 18.9% 6.12% 3.1% 0% Severity score 2.9 1.83* 0.69** 0.14** 0.14** 0** 100% 63.1% 23.8% 4.85 4.85 0% * significant, ** highly significant
- 33. 33 Mean symptom score (%) before & after treatment with Betahistine 16 mg t.i.d. (n=29) Bradoo RA, Ind. J. Otolaryngol H N S, 2000, 52 (2), 151-8 100 100 100 18.9 23.8 4.7 6.1 4.8 26.6 0 20 40 60 80 100 120 Frequency Duration Severity wk 0 wk 2 wk 3 Symptomscore%
- 34. 34 Mean symptom score of patients with acute vertigo attacks at baseline (n=18) Bradoo RA, Ind. J. Otolaryngol H N S, 2000, 52 (2), 151-8 Parameter Weeks of Betahistine treatment 0 1 2 3 Frequency 14.39 4.94* 3.89** 0** 100% 30.5% 27% Duration 23.19 6.27** 0.15** 0** (min) 100% 27% 0.7% Severity score 3.0 1.94* 0.67** 0** 100% 64.7% 22.3% * significant, ** highly significant
- 35. 35 Mean symptom score (%) of patients with acute vertigo attacks at baseline ( n=18) Bradoo RA, Ind. J. Otolaryngol H N S, 2000, 52 (2), 151-8 100 100 100 27 0.70 0 0 64.7 34.3 27 22.3 0 20 40 60 80 100 120 Frequency Duration Severity wk 0 wk 1 wk 2 wk 3 Symptomscore%
- 36. 36 Global evaluation (n=29) Parameters Excellent-good rating in % of patients by Patients Physicians Efficacy 100%100% Tolerance 100%100% Effect on associated 95%95% symptoms Bradoo RA, Ind. J. Otolaryngol H N S, 2000, 52 (2), 151-8
- 37. 37 Effect of Betahistine on associated symptoms in vertigo patients Associated No. of Vertigo patients Symptom Weeks of treatment wk 0 wk 1 wk 2 wk 3 Tinnitus 15 7 1 0 Nausea/Vomiting 6 0 Total no. of patients with vertigo = 29 Bradoo RA, Ind. J. Otolaryngol H N S, 2000, 52 (2), 151-8
- 38. 38 15 7 1 0 6 0 0 2 4 6 8 10 12 14 16 No.ofvertigopatients Tinnitus nausea/ vomiting wk 0 wk 1 wk 2 wk 3 Improvement of associated symptoms in vertigo patients with Betahistine Bradoo RA, Ind. J. Otolaryngol H N S, 2000 June, 52 (2), 151-8
- 39. 39 Tolerance of the treatment No drop-outs due to side effects No gastrointestinal disturbances None of the patients experienced drowsiness Drug treatment did not affect quality of life in any patient Bradoo RA, Ind. J. Otolaryngol H N S, 2000, 52 (2), 151-8
- 40. 40 Conclusion Excellent efficacy of Betahistine at dose of 16 mg t.i.d. Excellent tolerance of Betahistine at this dose without side effects - drowsiness, G.I. disturbances Very effective in management of acute vertigo Bradoo RA, Ind. J. Otolaryngol H N S, 2000, 52 (2), 151-8
- 41. 41 Highlights of the trial First Indian Trial of Vertin at a specific dose of 16 mg t.i.d. in medical College Vertin at a dose of 16 mg t.i.d offers faster and better results. 93 % patients completely relieved within 3 weeks of the therapy Also proves the excellent tolerance of Betahistine at a dosage of 16 mg t.i.d. Focus on new insight into the management of acute cases with this therapy Bradoo RA, Ind. J. Otolaryngol H N S, 2000, 52 (2), 151-8
- 42. 42 Pre and post Betahistine therapy 99m Tc HMPAO BRAIN SPECT studies in patients with vertigo Dr. B.A.Krishna, Head - Nuclear Medicine, Dr. M. V. Kirtane, H.O.D. ENT Dept. P.D. Hinduja Hospital, Mumbai Neurology India, Sept. 2000, 48 , 255-9 To observe the effects of Betahistine on different hypoperfused areas of brain in vertigo patients
- 43. 43 SPECT Principle (Single Photon Emission Computed Tomography) HMPAO labeled with 99m TC- Lipophilic compound taken by brain tissue Can quantitate the blood perfusion in different areas of brain based on color scale Uptake depends on blood perfusion of brain Decay of this compound leads to emission of high energy photons-counted by gamma camera Images reconstructed to obtain transaxial, sagittal, coronal views Krishna BA, Kirtane MV, Neurology India, 2000,48, 255-9
- 44. 44 Vertin - SPECT study Part I - Vertigo patients consulting neurotologists with a probable diagnosis of ischemia of areas of brain -included in the trial Part II - Patients subjected to baseline SPECT images in Nuclear Medicine Department to identify hypoperfusion in different areas of brain Part III - Patients with hypoperfusion given Betahistine 16 mg t.i.d. and clinical examination done every week by Neurotologist for symptoms Part IV - SPECT repeated to observe effects of drug on hypoperfusion, quantify the same and correlate with the clinical improvement Krishna BA, Kirtane MV, Neurology India, 2000,48, 255-9
- 45. 45 SPECT Results No. patients entered the study 11 No. of patients with normal perfusion at baseline 2 No. of patients with hypoperfusion at baseline 9 Patients lost to follow- up 2 No. of patients who completed the study 7 Complete Improvement 6 Partial improvement 1 Krishna BA, Kirtane MV, Neurology India, 2000,48, 255-9
- 46. 46 99m Tc HMPAO transaxial images of brain (6mm slices) P.D. Hinduja National Hospital, Mumbai Figure I: The top row images show HYPOPERFUSION in the left temporal lobe prior to therapy & the bottom row images of the same patient show complete NORMALISATION OF PERFUSION after 4 weeks of Betahistine therapy 16 mg three times daily Pre-Betahistine Therapy (15.06.1999) No. 2540 Post-Betahistine Therapy (12.07.1999) No. 2922 Reference Image SPECT MRI R L R L Krishna BA, Kirtane MV, Neurology India, 2000,48, 255-9
- 47. 47 99m Tc- HMPAO transaxial images of brain (6 mm slices) P.D.Hinduja National Hospital, Mumbai Figure II: The top row images show HYPOPERFUSION in the right inferior cerebellar region prior to therapy. The bottom row images show almost complete NORMALISATION OF PERFUSION following 2 weeks of Betahistine therapy 16 mg three times daily. Pre-Betahistine Therapy (27.02.1998) No.791 Post-Betahistine Therapy (10.03.1998) No. 1950 Reference Image SPECT MRI R L R L Krishna BA, Kirtane MV, Neurology India, 2000,48, 255-9
- 48. 48 99m Tc- HMPAO sagittal images of brain (6 mm slices) P.D. Hinduja National Hospital, Mumbai Figure III: The top row images show a well-defined focalized HYPOPERFUSION in the right parieto-occipital region prior to therapy. The bottom row images show almost complete NORMALISATION OF PERFUSION of this region after 3 weeks of Betahistine therapy 16 mg three times daily. Pre-Betahistine Therapy (17.03.1999) No.1086 Post-Betahistine Therapy (08.04.1999) No.1599 Reference Image SPECT MRI R L R L Krishna BA, Kirtane MV, Neurology India, 2000,48, 255-9
- 49. 49 Regional distribution of perfusion abnormalities and improvement Areas No. of hypoperfused No. of areas areas at baseline improved with Betahistine Temporal 9 7 Cerebellar 4 4 Parieto-occipital 5 3 Total 18 14 Krishna BA, Kirtane MV, Neurology India, 2000,48, 255-9
- 50. 50 Conclusion 99m Tc - HMPAO Brain SPECT - an important diagnostic tool Betahistine at a dose of 16 mg t.i.d. is an effective antivertigo therapy which improves blood perfusion to hypoperfused areas of brain in vertigo patients Ischemia of cerebellar region which is the main cause of vertigo showed complete normalization of perfusion with Betahistine therapy. Krishna BA, Kirtane MV, Neurology India, 2000,48, 255-9
- 51. 51 CLINICAL STUDIES BETAHISTINE VS. MAJOR COMPETITORS CINNARIZINE PROCHLORPERAZINE
- 52. 52 0 2 4 6 8 10 12 14 16 18 1 2 3 4 5 6 months Meanno.ofattackspermonth Betahistine Significantly better than Cinnarizine in reducing frequency of vertigo attacks Adapted from Deering et al, Curr. Med. Res & Opin, (1986), 10(4), 209-214 Betahistine Cinnarizine
- 53. 53 Cinnarizine 18% 0% Betahistine 18% drop-outs due to drowsiness in patients reporting side-effects with Cinnarizine treatment. Adapted from Deering et al, Curr. Med.Res & Opin,(1986), 10(4), 209-214
- 54. 54 A comparison of Betahistine and Cinnarizine Betahistine Cinnarizine No drowsiness Drowsiness - side effect Facilitates compensation slows down compensation Suitable for use with should not be used with vestibular habituation vestibular habituation therapy therapy Kirtane MV, Ind. J. Otolaryngol H N S, 1999, 51 (2), 27-36 , Colletti V, Acta Otolaryngol Suppl 544, 27-33.
- 55. 55 Double- blind crossover trial of Betahistine vs. Prochlorperazine Vs. Placebo 12 healthy volunteers High dosage of Betahistine used (72 mg tds for 3 days) Subjects performed driving tests weaving in & out of traffic cones driving through a narrow gap between traffic cones Assessed carelessness (Hitting cones!), errors of judgement and slowing of response Betts,Brit. J. Clin. Pharmacol, 1991, 32, 455-8
- 56. 56 Driving test: mean number of cones hit 9.0 5.5 4.0 Prochlorperazine Betahistine Placebo Bettts, Brit. J. Clin. Pharmacol, 1991, 32, 455-8
- 57. 57 Betahistine : Summary Improves cerebral & cochlear blood flow Reduces resting firing of ampullar receptors without affecting evoked responses Provides faster relief & better efficacy in relieving vertigo Free from drowsiness Facilitates vestibular compensation Offers a dose-dependent effect Relieves associated symptoms like nausea, vomiting, tinnitus
- 58. 58 Betahistine Features Improves cochlear and cerebral blood flow Regulates firing activity of vestibular nuclei Dose dependent effect Does not slow down compensation Benefits Prophylactic effect by reducing frequency of vertigo attacks Symptomatic relief by reducing severity of attacks Higher the dose, better the action. Higher dose useful for acute attacks Suitable for use with Vestibular Habituation therapy
Editor's Notes
- <number> Study Design : double-blind , cross-over No. of patients : 50 adult patients with Vertebrobasilar arterial insufficiency (VBI) with dementia Two treatment periods of 6 wks.each. . Grp I (n=29) Betahistine (32mg/d) for 1st period followed by identical placebo in IInd period, Grp II (n=21) Reverse order. Assessment :Evaluations made initially & at intervals of 6 weeks each , included detailed assessment of neurologic functions according to quantitative scale. Neuropsychologic tests included Wechsler Adult Intelligence scale(WAIS), Wechsler Memory Scale, Halstead - Wepman Aphasia Screening Test (Reitan Modification), Reitan Trailmaking Test, Finger Tapping Test , Tactual Performance Test for elderly & Reitan Sensory- Perceptual Examination. Regional cerebral blood flow measurements were carried out in 15 patients using intracarotid injections of xenon133 & gamma camera.
- <number> Out of 15 patients , only in 5 patients the assessment was complete at all intervals. Administration of placebo resulted in a mean decrease of 2.6 % in mean regional Cerebral Blood Flow (rCBF) (p < 0.05) whereas administration of Betahistine resulted in mean increase of 14.8 % in mean rCBF (p < 0.025). The difference between placebo & Betahistine was significant at (p < 0.005).
- <number> This electrophysiological study, by Japanese researchers studied effects of Betahistine on neuron activity of Lateral Vestibular Nucleus (LVN). No.of sub : 30 adult cats Method : A bipolar electrode for stimulation of vestibular nerve was inserted through round window of middle ear in cats & single neuron activity was recorded as spike generated on an oscilloscope. Betahistine mesylate was intravenously injected at cumulative doses of 0.1, 1 & 5 mg/kg at 20 min intervals. Betahistine was also administered iontophoretically, i.e. directly by means of an electric current & effect on spike generation was observed. Results :Spike generation of monosynaptic neurons remain unaffected by i.v. & iontophoretic administration of Betahistine. Spike generation of polysynaptic I neurons was inhibited by i.v. Betahistine in a dose-dependent manner (As in graph). Spike generation of polysynaptic I neurons was also inhibited by iontophoretic admin. of Betahistine in a dose-dependent manner (not shown in graph).
- <number> Dose-dependent inhibitory effect of Betahistine on spike generation of LVN neurons was similar with both i.v. & iontophoretic application. This suggests that inhibition is due to direct action of the drug on polysynaptic neurons, not resulting from an indirect effect such as increase in blood flow in brain stem.
- <number> Study design: double-blind, randomized, placebo-controlled, cross-over, multicenter. No. of patients : 114 patients suffering from paroxysmal vertigo attacks of various origin Treatment period : 2 treatment periods of 5 wks each. Grp I (n=38) Betahistine (16 mg t.i.d) for 1st period , then identical placebo for 2 nd period . Grp II :(n=44). Two treatments in reverse order. Results :analyzed in 82 patients. As shown in graph, during 1 st treatment period, Betahistine gave a significant improvement in contrast to placebo. When patients crossed over from Betahistine to placebo, no further improvement could be found. While crossing over from placebo, Betahistine gave a better result although not significant. (p= 0.06). Comparison of all Betahistine treatment periods with placebo showed a significant change in frequency of attacks in favor of Betahistine (p = 0.006). Thus Betahistine treatment provides prophylactic effect by causing significant reduction in frequency of attacks which could be explained by modulation of cerebral & labyrinthine circulation.
- <number> As shown in graph, during 1 st treatment period, Betahistine significantly diminished severity of attacks while placebo did not. After crossing over Betahistine gave further , though not significant, improvement while placebo gave a slight deterioration . Comparison of all Betahistine treatment periods with placebo showed a significant difference in favor of Betahistine (p= 0.02) with respect to change in severity of attacks. Betahistine treatment thus provides symptomatic effect by reducing severity of attacks which may be explained by inhibition of vestibular nuclei firing.
- <number> Study Design : double-blind, multicenter No. of patients : 81 with recurrent paroxysmal vertigo attacks with or without cochlear symptoms typical of Meniere’s disease. Treatment period of 90 days with either Betahistine (dosage 16 mg t.i.d. = 48 mg/d) or identical placebo Results were analyzed in 72 patients (36 Betahistine , 36 Placebo) The average monthly intensity expressed according to a scale increased gradually from a score of 1 (simple discomfort ) to 5 ( bedridden) showed a numerical decrease which was always in favor of Betahistine as compared with placebo (as shown in graph). This difference was statistically significant on day 90 (p= 0.02). After 3 months of treatment , the patients with Betahistine had an average intensity score of 0.53 while those with placebo had an average score of 1.79 .
- <number> At the three examination times on day 30, day 60 & day 90, the patients who no longer had vertigo symptoms were recorded for each treatment group. From the first month onwards, twice the no. of patients were in remission with Betahistine than with placebo. The results were always in favor of Betahistine. The positive results increased with the duration of the treatment. After 3 months of treatment , nearly three quarters of the patients treated with Betahistine no longer had vertigo symptoms.
- <number> Following ref. Shows that Betahistine increases cochlear blood flow in a dose-dependent manner. -- Laurikainen EA et al, Am.J. Otol, (1993),14,1 Hence dose-dependent effect of Betahistine in vascular effect, neuron activity, & on nystagmus is shown. Hence higher the dose, better & faster are the effects of Betahistine. Also Betahistine 16 mg t.i.d. is more effective than 8 mg t.i.d.. This dose-dependent effect of Betahistine implies that by doubling the dose of Betahistine from 8 mg t.i.d. to 16 mg t.i.d. , faster & better will be its effect.
- <number> Study Design : double-blind , randomized No. of subjects : 10 normal subjects 23-30 yrs. of age Method : Vestibular nystagmus was induced by means of a torsion swing. The oscillation time of the swing was kept constant .Each individual received 3 different single oral doses of Betahistine (8, 16, & 32 mg) on 3 different occasions with an inter-test interval of 1 wk. Assessment :The duration of nystagmus, following drug administration was calculated as a % of pre-treatment duration. The duration of nystagmus was measured before administration of the drug & at 1/2 , 1, 2, 3, 4, 6, 8 hr. after.
- <number> The graph shows that Betahistine reduces duration of nystagmus in a dose-dependent manner. 16 mg Betahistine was more effective (p< 0.0005) in reducing duration of nystagmus (mean reduction 48 %) than 8 mg Betahistine (mean reduction 35 %). Further 32 mg Betahistine was more effective (p< 0.0005) (mean reduction 59 %) than 16 mg Betahistine. Also note, higher the dose, faster is the action of Betahistine. This can be explained by considering any particular % reduction in duration of nystagmus, say 20 % reduction (i.e. 80 % of the initial duration of nystagmus), time required by 32 mg Betahistine is lesser than that for 16 mg which in turn is lesser than that for 8 mg. Hence higher the dose of Betahistine, better & faster is its action.
- <number> This American study determined the side effects which may occur with Betahistine. No. of subjects : 10 normal captive males Treatment period :Gr. I (n=5) Betahistine 4 x 4 mg daily, Gr. II (n=5) Betahistine 4 x 12 mg daily , both for 60 days. Assessment parameters : blood pressure, pulse etc. Each patient was interrogated daily & the sitting blood pressure , pulse etc. was recorded before & after 60 days of medication. Results :The above graph represents the systolic & diastolic blood pressure before & after 60 days of medication. The average of all the 10 subjects is considered. There were no changes of statistical significance in blood pressure, pulse after treatment with Betahistine. Hence Betahistine does not cause any adverse side effects which will affect CVS.
- Whole labyrinth was isolated from frog.Posterior canal with ampullary nerve was micro-dissected free and bathed in artificial periplymph fluid. Nerve firing rate ( both in resting and evoked ) from ampullary nerve was recorded. 3 Betahistine metabolites were administered to the preparation by perfusion of bath. M1 (aminpethyl pyridine), M2 (hydroxyethyl pyridine), M3 (pyridyl acetic acid). Vertigo is generally produced by imbalance or sudden, uncontrolled vestibular firing activity. Hence it is desirable that antivertigo drug should reduce the resting firing rate. Evoked response is the firing or impulse which gives information on the stimuli e.g. sudden head movement etc. Hence to maintain the normal vestibular sensitivity it is desirable that antivertigo drug should not hamper the evoked response.
- The two metabolites M2 and M3 were completely inactive. Only one metabolite M1 was effective or active. M1 produced the progressive reduction in the ampullar resting firing rate without affecting evoked response.
- This study being the research study in this field, we can not comment whether dosage adjustment is possible with Betahistine since Metabolite is active. Future studies in this area may focus more details on this aspect.
- This open prospective study was carried out as an out patient trial. All patients received 16 mg tds for 6 weeks or earlier till remission of attacks. Any other antivertigo medication was stopped. Patients were included one week after stoppage of the earlier therapy.
- Global evaluation: Patients as well as clinicians assessed the overall efficacy of the treatment, tolerance, effect on associated symptoms on a four-point scale as excellent, fair, good poor.
- Overall 29 patients were analyzed. The above are the scores of the 3 parameters frequency, duration, severity of vertigo attacks. Kindly note that by week 3, almost 95 % reduction is seen in all the 3 parameters. A statistically significant improvement was seen from the first month itself.
- The most interesting aspect of this study was the sub-group analysis of patients with severe vertigo attacks at baseline. (n=18). Kinldy note that the earlier graph shows results of all (acute attacks) the 29 patients in the study. While this table and graph shows the results of only 18 patients with sever vertigo attacks at baseline. A statistically significant improvement was seen from 1 st week itself in these acute vertigo cases with Betahistine. By week 3 all the patients with acute or severe vertigo attacks were completely free of attacks.
- This graph shows the improvement of patients with sever or acute attacks at baseline (n=18) ( for values refer the table on earlier slide). By week 3 all the patients with acute attacks were completely free of vertigo.
- Both physicians as well as patients rated the overall efficacy and tolerance of the treatment to be excellent to good in 100 % patients. Effect on associated symptoms such as nausea, vomiting was rated as excellent to good in 95 % patients. The rating of both physicians and patients is equivalent . This indicated that there was no placebo effect.
- 15 patients suffered from tinnitus at baseline. 14 patients completely relieved after 2 weeks of therapy. On completing 3 weeks of therapy, no patient was complaining of tinnitus. Six patient complained of nausea and vomiting. Treatment with Betahistine relieved this associated symptom on completing just 1 week of therapy.
- Dr. Krishna , H.O.D. - Nuclear Medicine is very well known in his field. Dr. Kirtane , H.O.D. ENT dept. is an eminent neurotologist in India. Hinduja Hospital is one of the well recognized hospital in Mumbai. This study was published in Neurology India. This prestigious journal is indexed journal and an official publication of Neurological society of India (N.S. I.). Vertigo due to vascular insufficiency to brain is very common. SPECT (Single Photon Emisssion Computed Tomography) is emerging as a powerful diagnostic tool for vertigo in nucleaar medicine. Betahistine an antivertigo drug known worldover is shown to increase cochlear micirculation .Old clincial studies have also shown that it increase scerebral blood flow in patients with VBI (vertebrobasilar insufficiency) . This present study was undertaken to detect and quantify the hypoperfused areas in vertigo patients, to assess the effects of Betahistine in improving this hypoerfusion to brain using SPECT
- Brain SPECT uses a lipophilic molecule such as HMPAO ( hexa methyl propylene amine oxime) that crosses the blood brain barrier. It is labeled with a conventional single photon emitters such as Technetium (Tc). The labeled molecule 99m -Tc- HMPAO is lipophilic and crosses the blood brain barrier. Brain uptake is proportional to blood perfusion to brain.The physical decay of this compound leads to emission of single photons directly from radionuclide. SPECT instrument comprises a gamma camera that detects single photons. The SPECT imaging device collects information in a 360o circle around the brain and generates a three-dimensional image that can be displayed in a transaxial, coronal and sagittal views. The image display uses a radiographic grey scale or can be converted to a color scale. For clinical purposes,a qualitative image locating the areas is important. For quantitaive purposes, the blood flow can be be measured in particular region as region of Interest.
- <number> Study Design : double-blind , crossover, No.of patients:88 patients with peripheral vertigo of unknown origin Two treatment periods of 3 months each . Grp I Betahistine (24 mg t.i.d.for 1st period then Cinnarizine 30 mg t.i.d. in 2nd period. Grp II :reverse order Assessment : Severity, duration,intensity of attacks, side effects. Results : Both drugs were equally effective in reducing severity & duration of attacks. As shown in the graph, Betahistine was significantly better in reducing the no. of attacks.When patients crossed over from Betahistine to Cinnarizine , they suffered a sharp increase in no. of attacks during 1 st month. , there was a small decrease in 2 nd & 3 rd month , but frequency was still double of that achieved after 3 months on Betahistine. When patients crossed over from Cinnarizine to Betahistine, frequency of attacks continued to decrease. Comparing last two months of each treatments, frequency of attacks with Betahistine treatment was significantly less (p=0.025) than that with Cinnarizine.
- <number> Polysynaptic I neurons is one of the sites involved in the occurrence of vertigo. Vertigo is generally produced by imbalance in bilateral vestibular function or massive impulses from peripheral organs. Antivertigo action of Betahistine could be explained as inhibition of massive impulses to the polysynaptic neurons of the LVN. In contrast to Betahistine, Cinnarizine produced an enhancement of responsiveness of LVN mono & polysynaptic neurons in a non dose-dependent manner. Hence Cinnarizine may prevent vestibular disorders such as vertigo by increasing cerebral blood flow , but not by directly exciting LVN neurons. Betahistine has the benefit of giving dose-dependent effect which is not the case with Cinnarizine.
- With the both the tests, effects of Betahistine could not be distinguished from those of placebo. Even at high doses, Betahistine did not appear to impair driving performance. By contrast, Prochlorperazine, impaired driving performance, casuinb increased carelessness, (hitting more cones as shown above), errors of judgement (trying to drive between the cones which were not wide enough apart), some slowong of response. Improtantly the subjects were usually unawre of their impaired performance whilest on Procholrperazine. As shown above, while on betahistine, there were 5.5 cones hit, and 4.0 when on placebo. With Procholrperazine, there were 9.0 cones hit.
- <number> Betahistine offers all the benefits expected from a true Antivertigo drug. It has proven efficacy of improving cochlear , cerebral blood flow, normalizing firing frequency of vestibular nuclei & hence provides faster & better relief to vertigo patients. It has a dose-dependent effect. Betahistine is well tolerated & does not cause drowsiness. The interesting aspect is that it allows the normal adaptation process in vertigo patients.