Kombinasi flunarizin dan betahistin pada penyakit Meniere


Last update: June 3, 2018

Saya menambahkan kedua obat tersebut karena dari dulu memang sudah sering “diadu” efikasinya. Paper tertua yang saya temukan sudah terdokumentasi thn 1988 yang dimuat di Acta Otolaryngol Suppl, 460:143-8,

Flunarizine and betahistine. Two different therapeutic approaches in vertigo compared in a double-blind study.

Kemudian laporan dari penelitian Albera dkk 2003, menyatakan betahistin lebih baik dibanding flunarizin pada pasien dengan vertigo vestibular kambuhan.

Berikut saya lampirkan hasil yg sudah diringkas oleh Dynamed berikut. Alih-alih menggunakan obat ini sendiri-sendiri, kedua obat ini dipadukan untuk menghasilkan efek yang superior (interaksi keduanya tidak diketahui).

betahistin

Update 2018

Betahistine

  • consider a trial of betahistine (a histamine H3 receptor antagonist and weak H1 agonist) to reduce frequency and severity of vertigo attacks(26)
    • suggested dosing regimen 16 mg orally 3 times/day
    • betahistine is inexpensive and generally well-tolerated
    • stop treatment if no improvement in frequency of attacks
  • betahistine might improve vertigo symptoms in patients with Meniere disease (level 2 [mid-level] evidence)
    • based on Cochrane review with wide confidence interval and systematic review without assessment of trial quality
      • Cochrane review of 17 randomized trials comparing betahistine vs. placebo in 1,025 adults with vertigo
      • 5 trials enrolled patients with clinically defined Meniere disease
        • betahistine dose ranged from 16 to 36 mg/day
        • treatment duration ranged from 2 weeks to 3 months
      • no significant difference in symptom improvement (risk ratio 1.56, 95% CI 0.92-2.65) in analysis of 3 trials with 139 patients, but wide confidence interval cannot exclude clinically important differences
      • Reference – Cochrane Database Syst Rev 2016 Jun 21;(6):CD010696
    • systematic review of 12 randomized trials and randomized crossover trials comparing betahistine vs. placebo in 921 patients with Meniere disease or vestibular vertigo
      • betahistine administered orally in divided doses with total daily dose ranging from 24 to 48 mg with a treatment duration of ≥ 1 month (range 1-3 months)
      • compared to placebo, betahistine associated with improved vertigo symptoms
        • overall (odds ratio [OR] 2.42, 95% CI 1.86-3.16) in analysis of all 12 trials with 921 patients
        • in patients with Meniere disease (OR 3.35, 95% CI 2.16 -5.19) in analysis of 6 trials with 333 patients
        • in patients with vestibular vertigo (OR 2.02, 95% CI 1.4-2.93) in analysis of 7 trials with 693 patients
      • Reference – Eur Arch Otorhinolaryngol 2014 May;271(5):887
  • betahistine therapy reported to improve hearing function in patients with unilateral Meniere disease (level 3 [lacking direct] evidence)
    • based on case series
    • 200 patients (mean age 45 years) with untreated unilateral Meniere disease had betahistine with follow-up at 6 months
      • initial dosing regimen 16 mg orally 3 times daily with food
      • maintenance treatment was 24-48 mg/day orally in divided doses to control symptoms
    • general recommendations made for low sodium diet but no other medications allowed during the study period
    • compared to baseline, mean hearing level decreased (indicating an improvement) from 33.3 dB to 26.97 dB at follow-up (p < 0.001)
    • Reference – Braz J Otorhinolaryngol 2016 Sep-Oct;82(5):500 full-text
  • comparative efficacy of betahistine to other treatments for recurrent vertigo
    • high-dose betahistine appears as effective as intratympanic dexamethasone injection for vertigo control at 12-months in patients with Meniere disease (level 2 [mid-level] evidence)
      • based on small randomized trial
      • 66 patients (mean age 60 years) with unilateral Meneire’s disease were randomized to high-dose betahistine plus placebo injections vs. intratympanic (IT) dexamethasone injections plus placebo tablets
        • high-dose betahistine given as 48 mg orally 3 times/day (total 144 mg/day)
        • IT dexamethasone given as 4 mg injections every 3 days (3 injections every 3 days)
      • 59 patients completed treatment and were available for follow-up at 12 months
      • number of vertigo attacks/month at baseline
        • 8.6 in betahistine group
        • 7.9 in IT dexamethasone group
      • both treatments associated with significant reductions in number of vertigo attacks/month
      • comparing high-dose betahistine vs. IT dexamethasone for control of vertigo at 12 months
        • complete control in 41% vs.47% (not significant)
        • substantial control in 17% vs. 20% (not significant)
      • side effects in betahistine group included stomach fullness (4 cases), diarrhea (3 cases), nausea (4 cases), headache (7 patients), and mild vegetative symptoms (6 patients)
      • Reference – Am J Otolaryngol 2015 Mar-Apr;36(2):205
    • addition of nimodipine to betahistine appears more effective than betahistine alone in patients with Meniere disease (level 2 [mid-level] evidence)
      • based on cohort study
      • 113 patients with Meniere disease evaluated
        • 60 patients treated with betahistine 16 mg orally twice daily plus nimodipine 20 mg orally twice daily
        • 53 patients treated with betahistine 16 mg orally twice daily alone for 6 months
      • comparing betahistine plus nimodipine vs. betahistine alone
        • functional level score 1 or 2 (no dizziness or minimal dizziness) in 71% vs. 38% (p < 0.001, NNT 4)
        • stage 1 or 2 hearing (< 40 decibel [dB] threshold) in 42% vs. 32% (p < 0.05, NNT 10)
      • Reference – Acta Otorhinolaryngol Ital 2012 Dec;32(6):393 full-text
  • review of betahistine for treatment of Meniere disease can be found in Neuropsychiatr Dis Treat 2007 Aug;3(4):429 full-text
Diuretics

  • diuretics are widely used in treatment of Meniere disease but may have adverse effects, especially in older patients, and strong evidence for efficacy is lacking(16)
    • diuretics affect ion pumps and ionic gradients in the ear and kidney
    • therapeutic effect of diuretics theorized to work via influence on inner fluid and electrolyte processing, but strong evidence for efficacy is lacking
  • no high-quality randomized trials evaluating diuretics for Meniere disease
Corticosteroids

  • intratympanic dexamethasone
    • consider intratympanic (IT) dexamethasone in patients with vertigo refractory to lifestyle changes, betahistine, and diuretics(5)
      • exact mechanism of action unknown, but dexamethasone is an immune modulator so it may be effective in patients with Meniere disease that is autoimmune in nature
      • corticosteroids such as dexamethasone may influence sodium and fluid dynamics in the inner ear due to their mineralocortocoid properties
    • intratympanic dexamethasone may reduce vertigo and hearing loss in patients with Meniere disease (level 2 [mid-level] evidence)
      • based on small randomized trial
      • 22 adults with untreated Meniere disease were randomized to intratympanic (IT) dexamethasone 4 mg/mL vs. placebo per day for 5 days
      • 4 (36%) placebo patients dropped out due to need for treatment
      • comparing IT dexamethasone vs. placebo at 2 years
        • complete vertigo control in 9 patients (82%) vs. 4 patients (57%) (p < 0.001, NNT 4)
        • improvement in hearing loss in 35% vs. 10% (p < 0.001, NNT 4)
      • Reference – Otolaryngol Head Neck Surg 2005 Aug;133(2):285
      • no additional trials found in Cochrane review of intratympanic steroids for Meniere disease (Cochrane Database Syst Rev 2011 Jul 6;(7):CD008514)
    • intratympanic dexamethasone reported to be effective for Meniere disease refractory to other treatments (level 3 [lacking direct] evidence)
      • based on 3 case series
      • case series of 43 patients (median age 44 years) with refractory Menieres disease had intratympanic (IT) dexamethasone 5 mg (1 ml) with follow-up at 18 months
        • at follow-up, IT dexamethasone associated with
          • complete vertigo control in 49% and substantial vertigo control in 21%
          • reduced tinnitus in 49%
          • alleviated or diminished aural fullness in 34.9%
        • no further hearing loss reported after administration of IT dexamethasone
        • Reference – Int J Clin Exp Med 2015;8(4):6016 PDF
      • case series of 100 patients (mean age 41 years) with refractory Meniere disease had slow injection of 0.4 to 0.5 ml IT dexamethasone (4 mg/ml)
        • IT dexamethasone associated with
          • improvement in pure tone audiometry (PTA) in 52% of 84 patients with baseline pure tone audiometry level greater > 20 decibels [db]
          • improvement in speech discrimination scores (SDS) in 35% of 73 patients with baseline abnormal SDS
          • improvement in tinnitus score in 57% of 87 patients with baseline tinnitus
        • Reference – Iran J Otorhinolaryngol 2014 Jul;26(76):129 PDF
      • case series of 159 patients (mean age 51 years) with unilateral Meniere disease refractory to dietary changes and medical therapy had ≥ 1 intratympanic (IT) dexamethasone treatment with mean follow-up 47 months
        • dosing regimen
          • dexamethasone 24 mg/ml applied transtympanically to middle ear in sequence of 3 perfusions for total of 1 ml (each injection 10 minutes apart)
          • follow-up visits performed every 3 months with patient given choice of further IT dexamethasone, IT gentamicin, endolymphatic sac surgery, surgical labyrinthectomy, or no treatment
        • treatment success defined as control of symptoms so no further treatment modalities required
        • 81% of patients had successful control of Meniere disease symptoms at 24 months of follow (no ablative surgery required)
        • 20% increased likelihood of symptom control with each successive perfusion sequence
        • Reference – Otol Neurotol 2014 Oct;35(9):1638
  • oral prednisone may decrease the frequency and duration of vertigo episodes and tinnitus in patients with Meniere disease (level 2 [mid-level] evidence)
    • based on small randomized trial without blinding
    • 16 patients with Meniere disease with limited vertigo control and severe disability were given diphenidol 25 mg/day plus acetazolamide 250 mg every 48 hours and randomized to prednisone 0.35 mg/kg orally vs. no additional treatment daily for 18 weeks
    • compared to no additional treatment, prednisone associated with reduced
      • frequency of daily vertigo episodes by 6 weeks (p < 0.01)
      • duration of vertigo episodes by 12 weeks (p < 0.05)
      • tinnitus by 18 weeks (p < 0.05)
    • no significant differences in aural fullness or hearing
    • Reference – Otol Neurotol 2005 Sep;26(5):1022
Other medications

  • intratympanic medications
    • intratympanic latanoprost may be associated with reduced vertigo and improved speech discrimination in patients with unilateral Meniere disease (level 2 [mid-level] evidence)
      • based on small randomized trial
      • 10 patients aged 39-65 years with unilateral Meniere disease were randomized to latanoprost 50 mcg/mL (0.2-0.4 mL) vs. placebo injected into middle ear once daily for 3 days
      • compared to placebo, latanoprost associated with reduction of vertigo or dysequilibrium (p = 0.039) and improved speech discrimination (p ≤ 0.05)
      • no significant differences in visual analog score assessments of hearing or tinnitus
      • Reference – Otolaryngol Head Neck Surg 2005 Sep;133(3):441
    • intratympanic lidocaine reported to be effective for treating vertigo in 70% of 40 patients with Meniere disease (level 3 [lacking direct] evidence)
      • based on case series
      • 40 patients with Meniere had intratympanic lidocaine
      • intratympanic lidocaine effective in treating vertigo in 70% of patients with Meniere disease
      • mean attack-free period of 12.6 months
      • Reference – B-ENT 2011;7(3):157
  • oral medications
    • proton pump inhibitors may be associated with decreased number of menieric attacks in patients with Meniere disease (level 2 [mid-level] evidence)
      • based on retrospective cohort study
      • 42 patients (mean age 57 years) with Meniere disease were evaluated for number of menieric attacks yearly
        • 18 patients had used PPI for gastro-protective reasons for at least 12 months (PPI group)
        • 24 patients had never used PPI (non-PPI group)
      • menieric attacks defined as vertigo plus any other signs or symptoms of hearing loss, tinnitus, or aural fullness
      • mean follow-up 22 months
      • comparing PPi group vs. non-PPI group at follow-up
        • < 1 menieric crisis per year in 72.2% vs 16.7% (p < 0.001)
        • > 1 menieric crisis per year in 27.8% vs. 83.3% (p < 0.001)
      • Reference – Swiss Med Wkly 2010 Oct 7;140:w13104 full-text
    • famciclovir does not appear to reduce vertigo in patients with Meniere disease (level 2 [mid-level] evidence)
      • based on small randomized trial
      • 23 patients with Meniere disease were randomized to famciclovir vs. placebo
      • reduced number of vertigo spells in 25% with famciclovir vs. 18% with placebo (not significant)
      • all patients had improvements in dizziness and health-related quality of life
      • no serious adverse events reported
      • Reference – Otolaryngol Head Neck Surg 2004 Dec;131(6):877

Bacaan lebih lanjut:

Artikel menarik tentang betahistin, suatu agonis lemah H1 tapi antagonis kuat terhadap H3, bisa ditemukan di sini: [Link]

 

 

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