Emerging pharmacotherapy of tinnitus

One in ten adults has clinically significant subjective tinnitus, and for one in hundred, tinnitus severely affects their quality of life. Despite the significant unmet clinical need for a safe and effective drug targeting tinnitus relief, there is currently not a single FDA-approved drug on the market. Even a drug that produces a small but significant effect would have a huge therapeutic impact. In the last few years, there have been significant advances in i) the understanding of the pathophysiology of the different forms of tinnitus, ii) the establishment of valid animal models and iii) the development of clinical trial methodology. A glimpse of hope is appearing in the horizon as an increasing number of pharmaceutical industries now have compounds targeting tinnitus in their pipeline.     

Current pharmacological treatments for tinnitus

Introduction: Tinnitus, the phantom perception of sound, is a highly prevalent disorder and treatment is elusive.

Areas covered: This review focuses on clinical research regarding pharmacological treatments for tinnitus. The authors searched PubMed databases for English language articles related to pharmacological treatment of tinnitus, published through August 2012. The keywords "tinnitus AND pharmacological treatment” and “tinnitus AND drugs” were used. The search focused on clinical trials, but was complemented by other articles and information from clinical trial registries.

Expert opinion: Despite the significant unmet clinical need for a safe and effective drug for tinnitus relief, there is currently no EMA- or FDA-approved drug on the market. Even a drug that produces a small but significant effect would have a huge therapeutic impact. At present, evidence-based pharmacological approaches are limited to the treatment of comorbidities such as depression, anxiety, or insomnia. In the last few years there have been significant advances in the understanding of the pathophysiology of the different forms of tinnitus, the establishment of valid animal models, and the development of clinical trial methodology. A glimpse of hope is appearing in the horizon as an increasing number of pharmaceutical industries now have compounds targeting tinnitus in their pipeline.     

耳鸣诊断方法 的新进展

尽管耳鸣并非全由器质性病变引起，但其对生活质量产生的不良影响及近年不断增高的发病率使其愈加受到重视。由于耳鸣是患者的主观感受，很难将其客观化。所以其发病机制的研究、病因的确定、诊断及治疗均是医学界的难题。经过几十年的深入研究．耳鸣的发病机制、诊断等各方面均已取得进展。笔者通过对近十年国内外文献报道的研究，总结耳鸣常规诊断方法 、影像学、量化、严重程度评估及听尼特删诊疗技术等的最新进展。     

Role of acamprosate in sensorineural tinnitus

Acamprosate with dual mechanism of action as glutamate antagonist and GABA agonist can be a potential target to decrease the severity of sensorineural tinnitus.

Objective:

(1)To study the effectiveness of acamprosate in providing subjective relief and objective improvement in patients having tinnitus of sensorineural origin. (2) To evaluate the adverse events related to the use of acamprosate and also determine the change in quality of life (QOL) parameters.

Materials and Methods:

The study was randomized double-blind, placebo controlled, crossover. Forty adult subjects (>18 years of age), of either sex with tinnitus of sensorineural origin, were administered either acamprosate 333 mg TDS or matched placebo for a period of six weeks followed by a washout period of one week. Drug therapy was switched for another six weeks in consonance with the crossover design. The effect of acamprosate and placebo on subjective relief and objective improvement was evaluated by using modified tinnitus severity, QOL scores and audiometry with tinnitus matching in frequency and loudness.

Results:

At the end of the study, the drug had shown a statistically significant improvement in reducing the tinnitus score in 92.5% of the patients and placebo with an improvement in 12.5% of the patients. The drug was well tolerated without any serious drug reactions.

Conclusion:

Acamprosate is an effective drug in treating the severity of sensorineural tinnitus without causing much of the side effects.KEY WORDS: Acamprosate, audiometry, sensorineural tinnitus, tinnitus matching     

Emerging pharmacotherapy of tinnitus

Tinnitus, the perception of sound in the absence of an auditory stimulus, is perceived by about 1 in 10 adults, and for at least 1 in 100, tinnitus severely affects their quality of life. Because tinnitus is frequently associated with irritability, agitation, stress, insomnia, anxiety and depression, the social and economic burdens of tinnitus can be enormous. No curative treatments are available. However, tinnitus symptoms can be alleviated to some extent. The most widespread management therapies consist of auditory stimulation and cognitive behavioral treatment, aiming at improving habituation and coping strategies. Available clinical trials vary in methodological rigor and have been performed for a considerable number of different drugs. None of the investigated drugs have demonstrated providing replicable long-term reduction of tinnitus impact in the majority of patients in excess of placebo effects. Accordingly, there are no FDA or European Medicines Agency approved drugs for the treatment of tinnitus. However, in spite of the lack of evidence, a large variety of different compounds are prescribed off-label. Therefore, more effective pharmacotherapies for this huge and still growing market are desperately needed and even a drug that produces only a small but significant effect would have an enormous therapeutic impact. This review describes current and emerging pharmacotherapies with current difficulties and limitations. In addition, it provides an estimate of the tinnitus market. Finally, it describes recent advances in the tinnitus field which may help overcome obstacles faced in the pharmacological treatment of tinnitus. These include incomplete knowledge of tinnitus pathophysiology, lack of well-established animal models, heterogeneity of different forms of tinnitus, difficulties in tinnitus assessment and outcome measurement and variability in clinical trial methodology.     

突发性耳聋患者耳鸣状况的危险因素研究

目的探讨突发性耳聋患者耳鸣状况的危险因素。方法收集2006年1月—2012年12月该院收治的507例突发性耳聋患者完整的病历资料,对其听力损失的程度、听力曲线的类型及治疗效果进行评定,对耳鸣响度进行分级。分析不同耳鸣程度的相关影响因素。结果 507例突发性耳聋伴耳鸣患者的耳鸣程度以3级所占的比例最大,为32.94%（167/507）;所占比例最低的为1级,为13.02%（66/507）;2、4级分别各占27.02%（137/507）。不同耳鸣程度的患者在年龄、性别、耳侧、不同听力损害程度及不同听力曲线类型等方面的分布情况相比,均无统计学差异（P〉0.05）。结论患者在年龄、性别、耳侧等方面的不同分布情况、不同听力损害程度及不同听力曲线类型等不同的突发性耳聋的听力学特征及治疗效果与耳鸣的严重程度并不存在相关性,并非造成突发性耳聋患者伴发不同严重程度耳鸣的独立的危险因素。     

天麻素联合利多卡因耳迷根穴位注射治疗特发性耳鸣的疗效分析

目的 探讨天麻素联合利多卡因耳迷根穴位注射治疗特发性耳鸣的疗效.方法 选取该院2012年5月-2015年12月收治的特发性耳鸣患者130例为研究对象,根据随机数字表法将其分为观察组(n=70)和对照组(n=60),其中对照组在基础治疗的基础上口服银杏叶制剂和金纳多口服片剂,观察组在对照组的基础上于耳迷根穴位注射利多卡因和天麻素.比较两组患者治疗前和治疗后耳鸣残疾量表(THI)评分、视觉模拟量表(VAS)评分、耳鸣响度、睡眠量表(SPIEGEL)评分、焦虑量表评分、抑郁量表评分和耳鸣分级的变化,评价两组的临床疗效.结果 治疗后,两组患者的THI评分、VAS评分、耳鸣响度、SPIEGEL评分、焦虑量表评分、抑郁量表评分和耳鸣分级较治疗前均明显降低,且治疗后观察组THI评分、VAS评分、耳鸣响度、SPIEGEL评分、焦虑量表评分、抑郁量表评分和耳鸣分级均低于对照组,两组比较均差异有统计学意义(P<0.05).对照组治疗的总有效率为58.3%,观察组治疗的总有效率为91.4%,两组总有效率比较差异有统计学意义(χ2=19.486,P<0.001).结论 耳迷根穴位注射天麻素和利多卡因可明显改善特发性耳鸣患者的生活质量,提高治疗特发性耳鸣患者的临床有效率.     

前列地尔配合早期高压氧治疗突发性耳聋耳鸣的临床效果观察

目的探讨前列地尔配合早期高压氧治疗突发性耳聋耳鸣的临床效果。方法收集2012年10月～2014年3月来本院就诊的突发性耳聋耳鸣患者72例,按照随机数字表法分为两组,研究组及对照组各36例,研究组采用前列地尔配合早期高压氧治疗;对照组采用葛根素治疗,比较两组纯音测听气导情况及临床效果。结果研究组及对照组治疗后纯音测听气导平均值与治疗前比较均有不同程度的降低,研究组治疗后降低的幅度高于对照组,差异有统计学意义（P〈O．05）,研究组治疗突发性耳聋的总有效率（88．89％）、耳鸣总有效率（87．5％）高于对照组（77．78％、73．91％）,差异有统计学意义（P〈0．05）。结论前列地尔配合早期高压氧治疗突发性耳聋耳鸣的效果较好,可以显著改善纯音测听气导平均值,提高治疗总有效率。     

不同年龄突发性耳聋的近期疗效观察

目的分析不同年龄突发性耳聋患者药物治疗的近期疗效。方法240例突发性耳聋患者,根据年龄不同分为A组(年龄30~40岁)、B组(年龄41~50岁)、C组(年龄51~60岁)、D组(年龄61~70岁),每组60例。四组患者均给予丹参川芎嗪注射液、甲钴胺注射液、前列地尔注射液、糖皮质激素、高压氧治疗。比较四组治疗前后言语频率平均听阈及不同发病时间患者疗效、不同听阈患者疗效、耳鸣患者疗效。结果治疗后,四组患者患耳言语频率平均听阈均低于本组治疗前,差异具有统计学意义(P<0.05);A组、B组患者治疗总有效率分别为73.33%、71.67%,均高于C组的53.33%、D组的50.00%,差异具有统计学意义(P<0.05)。以50岁为界,预后呈明显不良。四组发病时间≤7 d患者的治疗总有效率高于同组发病时间>7 d患者,差异具有统计学意义(P<0.05)。四组不同听阈患者总有效率组内比较差异具有统计学意义(P<0.05),听力损失越重,听阈越高,预后越差。四组耳鸣患者治疗总有效率比较差异无统计学意义(P>0.05)。结论病程对突发性耳聋的治疗效果有重要的影响,尽早治疗可以明显改善预后,随着年龄的增长,预后逐渐变差。听阈亦是影响预后的因素,听阈越高,预后越差。耳鸣的治疗效果与年龄无关。     

Drugs affecting the inner ear. A review of their clinical efficacy, mechanisms of action, toxicity, and place in therapy

Many drugs have a site of action within the inner ear. The list includes therapeutic, diagnostic and ototoxic agents. Therapeutic agents are most useful in cases of infections, endolymphatic hydrops, vascular insufficiency, vertigo of peripheral origin, autoimmune disease, otosclerosis (otospongiosis), sudden hearing loss and tinnitus. For infections, the most widely used anti-microbial agents are the penicillins and cephalosporins. There are no antiviral agents that have been proven useful for inner ear viral infections. However, steroids have been of some value for controlling some of the sequelae. Steroids have also been useful in conjunction with ampicillin in cases of syphilitic hearing loss. In cases of endolymphatic hydrops, the diuretics chlorthalidone, hydrochlorothiazide and acetazolamide have been useful. When diuretic and diet therapy cannot control endolymphatic hydrops, ototoxic drugs such as streptomycin have been used. In cases of vascular insufficiency within the inner ear, vasodilators such as carbon dioxide, papaverine, buphenine (nylidrin), naftidrofuryl (nafronyl) and thymoxamine have been recommended, but their true efficacy is questionable. Some success with betahistine has been achieved but the mechanism of this drug's action may be other than vasodilatation. Vertigo is best controlled with antihistamines and anticholinergics and with certain calcium channel blockers. Autoimmune inner ear disease appears to respond to a combination of steroids and cyclophosphamide. Although controversial, current pharmacotherapy for otosclerosis includes sodium fluoride. Sudden hearing loss is treated with a 'shotgun' combination of drugs and/or bed rest. There are as yet no drugs which can be used to routinely reduce tinnitus although some medications may help the patient tolerate the problem. Lignocaine (lidocaine) is useful in diagnosing, and very evanescently reducing, tinnitus. Glycerin (glycerol) is useful in diagnosing endolymphatic hydrops and may at times transiently reduce tinnitus. The drugs most noted for their ototoxicity are the aminoglycoside antibiotics, certain diuretics, non-steroidal anti-inflammatory agents, certain anticancer agents and some miscellaneous chemicals. Some new research drugs are in clinical trials for tinnitus, hearing loss and vertigo, and the rational search for new otopharmacotherapeutic agents is increasing.     

耳声发射在耳鸣患者中的应用分析

目的探讨耳声发射在耳鸣患者中的应用价值。方法对我院于2011年12月-2013年12月收治的84例听力正常患者进行分组,其中观察组44例为听力正常伴耳鸣患者,对照组40例为听力正常无耳鸣患者,分析和对比两组患者的畸变产物耳声发射检查情况。结果观察组在1.00、2.00、4.00和8.00kHz中的检出率分别为50.0%、45.5%、40.9%和43.2%,与对照组的100%、95.0%、97.5%和100%比较,差异有统计学意义（P〈0.05）。并且经治疗后,观察组除1.00kHz外,其余频率点的耳声发射反应幅值明显要优于治疗前（P〈0.05）。结论给予听力正常耳鸣应用耳声发射检查,能够对患者的耳蜗病变情况进行尽早诊断和及时治疗,临床应用价值相对较高,值得进一步推广和使用。     

甲泼尼龙和利多卡因治疗难治性突发性聋伴耳鸣的效果

目的:探析甲泼尼龙和利多卡因在难治性突发性聋伴耳鸣中的治疗效果,及对纯音听阈均值、不良反应的影响。方法:回顾性分析,选择2020年1月至2021年9月焦作市妇幼保健院收治的难治性突发性聋伴耳鸣患者160例作为研究对象,按随机数字表法分为对照组和观察组,各80例。对照组男45例、女35例,年龄（50.52±3.82）岁,...     

中西医结合治疗感音神经性耳鸣的疗效观察

目的探讨中西药结合治疗感音神经性耳鸣的疗效。方法感音神经性耳鸣患者60例60耳根据人院顺序分为两组——治疗组与对照组各30例，两组首先均口服盐酸氟桂利嗪治疗，在此基础上治疗组加用自拟中药汤治疗，两组患者均治疗30d。结果治疗组有效率为93．3％，对照组为66．7％，治疗组的临床疗效好于对照组（P〈0．05）。两组治疗前中医症状评分无明显差异。经过治疗后都有显著性下降，但是治疗组的中医症状评分下降幅度明显高于对照组（P〈0．05）。结论感音神经性耳鸣的听力恢复过程是一个漫长的过程，中西药结合治疗能够提高治疗疗效，改善临床症状，值得推广应用。     

前列地尔联合甲钴胺和长春西汀治疗急性耳鸣的疗效观察

目的探讨前列地尔注射液联合甲钴胺片和长春西汀片治疗急性耳鸣的临床疗效。方法选取2015年6月—2016年9月在天津中医药大学第一附属医院耳鼻喉科治疗的耳鸣患者87例,随机分为对照组(44例)和治疗组(43例)。对照组口服甲钴胺片,0.5 mg/次,3次/d;且口服长春西汀片,5 mg/次,3次/d。治疗组在对照组基础上静脉注射前列地尔注射液,10μg加入到生理盐水10 mL中,1次/d。两组均治疗2周。观察两组临床疗效,比较两组耳鸣临床症状评分和严重程度积分变化。结果治疗后,对照组和治疗组的总有效率分别为61.36%、86.05%,两组比较差异有统计学意义(P0.05)。治疗后,两组耳鸣发生环境、睡眠影响、持续时间、生活工作影响、情绪影响和主观感觉评分均显著下降,同组治疗前后比较差异有统计学意义(P0.05);且治疗组这些观察指标的下降程度明显优于对照组,两组比较差异具有统计学意义(P0.05)。治疗后,两组耳鸣严重程度积分均显著下降,同组治疗前后比较差异有统计学意义(P0.05);且治疗组耳鸣严重程度积分明显低于对照组,两组比较差异具有统计学意义(P0.05)。结论前列地尔注射液联合甲钴胺片和长春西汀片治疗急性耳鸣具有较好的临床疗效,可改善临床症状,具有一定的临床推广应用。     

耳鸣与焦虑情绪及睡眠障碍相关性的研究进展

耳鸣是耳部疾病中最常见的三大症状之一,在不同地区,有7%~35%的一般人群出现过耳鸣症状。焦虑情绪的出现会影响大脑识别有用信息的能力,从而使大脑向听觉神经系统发送不良信号导致听觉系统过敏甚至失认,睡眠的缺乏造成大脑中的代谢物无法清除并不断累积,增强了听觉系统的交感神经反应,这两种情况都可能导致并加重耳鸣的出现。笔者就耳鸣与焦虑情绪及睡眠障碍的相关性进行综述,研究结果提示,焦虑情绪和睡眠障碍与耳鸣密切相关,并且可能是耳鸣的重要影响因素。国内外有关耳鸣的多种评估方法较为成熟,可为临床上评估耳鸣的严重程度提供参考。     

Auditory and vestibular sequelae to traumatic brain injury: a pilot study

AIM: To investigate the incidence of persisting auditory and vestibular sequelae in a group of 30 young adults recovering from Traumatic Brain Injury (TBI). METHODS: 30 participants, aged 21-45 years, with TBI suffered 19 months to 27 years previously, underwent a semi-structured interview and pure-tone hearing test in their home. Participants who failed the hearing screen then undertook a more comprehensive audiological evaluation. RESULTS: A variety of sequelae to TBI were reported. These were interpreted as tinnitus (53%), vestibular dysfunction (83%), abnormal facial sensory symptoms (27%) and intolerance to loud/sudden noises (87%). Ten (33%) participants demonstrated significant sensorineural hearing impairment in addition to speech recognition performance significantly worse than would have been predicted from their hearing impairment. CONCLUSIONS: Findings from this study will be of benefit to health professionals working in this area of rehabilitation as they seek to provide functional assessments and devise programmes to treat the often devastating auditory processing problems of people recovering from TBI.     

A dose-response analysis of the effects of L-baclofen on chronic tinnitus caused by acoustic trauma in rats

Subjective tinnitus is a chronic neurological disorder in which phantom sounds are perceived. Drugs that increase GABAergic neurotransmission in the CNS are sometimes used as a treatment. One such drug is the GABA(B) receptor agonist L-baclofen. The aim of this study was to investigate the effects of L-baclofen on the psychophysical attributes of tinnitus in rats.The effects of 1, 3 or 5 mg/kg L-baclofen (s.c.) on the psychophysical attributes of tinnitus were investigated using a conditioned lick suppression model, following acoustic trauma (a 16 kHz, 110 dB pure tone presented unilaterally for 1 h) in rats. In pre-drug testing, acoustic trauma resulted in a significant increase in the auditory brainstem-evoked response (ABR) threshold in the affected ear (P < 0.008) and a significant decrease in the suppression ratio (SR) compared to sham controls in response to the 20 kHz tones, but not the broadband noise or the 10 kHz tones (P < 0.002). The 3 and 5 mg/kg doses of L-baclofen significantly reversed the frequency-specific decrease in the SR in the acoustic trauma group, indicating that the drug reduced tinnitus. Following washout from the 3 mg/kg dose, but not the 5 mg/kg dose, the significant decrease in the SR for the acoustic trauma group returned, suggesting a return of the tinnitus. These results suggest that L-baclofen should be reconsidered as a drug treatment for tinnitus. This article is part of a Special Issue entitled 'Post-Traumatic Stress Disorder'.     

耳鸣习服治疗耳鸣84例临床分析

目的探讨耳鸣习服疗法（TRT）治疗耳鸣的临床疗效。方法将84例以耳鸣为第一主诉的长期严重主观耳鸣患者采用习服疗法进行治疗。在治疗开始后2周、1个月和2个月时进行疗效评定。结果 2周时总有效率为71.43%,1个月为78.57%,2个月为82.14%。结论 TRT是临床治疗耳鸣的一种较理想的方法。     

从耳鸣响度看听阈提高的速度

目的　了解神经性渐进性耳鸣、耳聋患者的耳鸣响度与听阈提高速度的关系。方法　对 5 0例 (76耳 )神经性耳鸣并伴听阈提高的患者作纯音听阈及耳鸣响度的测试 ,并根据病程时间计算听阈提高速度。对 2 5耳耳鸣响度在≤ 10 d B听力级 (HL )的患者与 5 2耳耳鸣响度在 >10 d B HL的患者之提高速度进行比较 ,并进行统计学分析。结果　耳鸣响度≤ 10 d B的 2 4耳与 >10 d B的 5 2耳听阈之提高速度在 3 k Hz以上高频区差异有显著性 (P<0 .0 1)。结论　耳鸣响度大小与听阈提高速度有关联。听阈的提高速度随着耳鸣响度的加大而增快     

甲磺酸倍他司汀联合盐酸氟桂利嗪治疗耳鸣的效果及安全性分析

目的 探讨甲磺酸倍他司汀联合盐酸氟桂利嗪治疗耳鸣的效果及安全性。方法 选取2016年1月-2017年12月西宁市第一人民医院收治的耳鸣患者178例,按照治疗方法的不同分为对照组、观察组,每组89例。对照组给予盐酸氟桂利嗪进行治疗,5 mg/次,1次/d,疗程2周。观察组在对照组基础上联合甲磺酸倍他司汀进行治疗,12 mg/次,3次/d,疗程2周。比较两组的临床疗效、治疗前后耳鸣程度、听力水平及治疗期间不良反应的发生情况。结果 观察组临床疗效的总有效率（87.64%）显著高于对照组（42.70%）,差异有统计学意义（P<0.05）。治疗前两组患者的耳鸣评分差异不显著,治疗后两组患者的耳鸣评分均显著降低,同组治疗前后比较差异有统计学意义（P<0.05）;且观察组显著低于对照组,差异有统计学意义（P<0.05）。治疗前两组患者的听力水平差异不显著;治疗后两组患者的听力均显著降低,同组治疗前后比较差异有统计学意义（P<0.05）;且观察组显著低于对照组,差异有统计学意义（P<0.05）。两组不良反应发生率差异不显著。结论 甲磺酸倍他司汀联合盐酸氟桂利嗪治疗耳鸣的效果优于单纯使用盐酸氟桂利嗪,安全可靠,值得临床应用与推广。