Introduction
Migraine headaches frequently coexist with vestibular symptoms such as vertigo, motion sickness, and gait instability. Migraine-related vasospasm can also damage the inner ear which results in symptoms such as sudden sensorineural hearing loss (SSNHL) and tinnitus.1 The pathophysiology of these symptoms is not yet fully understood and despite their prevalence, there is no universally approved management.
Due to patient belief, non-universal effectiveness, cost, and fear of the side effects of conventional treatments, many patients with migraine-related symptoms seek complementary and integrative medicine (CIM) alternatives. Traditional medicine (acupuncture, herbal supplements, and manual therapies) originated in China about 3,000 years ago, then spread to Korea and Japan with Buddhism.2 However, some in the U.S. still regard CIM therapies with skepticism mainly because of the lack of randomized clinical trials.3,4 A cross-sectional study conducted between 2002 and 2012 reported that 33.2% of adults in the US use complementary health approaches (dietary supplements, deep-breathing exercises, and yoga),5 with 75% of patients not informing their physician about this practice.3 In this review, we summarize the data on CIM in treating patients with migrainous ear disorders (Tables 1–3).
Table 1:
Symptom | Alternative Medicine Interventions | Study | Study Nature | Sample Size | Key Findings |
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Tinnitus | CBT | Abouzari et al.7, 2021 | Randomized Controlled Trial | 30 Patients | Treatment group: Significant higher improvement in THI scores after smartphone-based CBT and sound therapy. |
McKenna et al.9, 2020 | Meta-analysis | CBT is an effective treatment for tinnitus distress. | |||
Cima et al.10, 2012 | Randomized Controlled Trial | 492 Patients | CBT group: a significantly improvement in QOL, decrease tinnitus severity and tinnitus impairment. | ||
Beukes et al.11, 2019 | Meta-analysis | 15 Studies | Tinnitus: significant favor of tinnitus iCBT over inactive and active controls. Hearing loss: no significant favor for either intervention. Study quality affected the outcome. |
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Andersson12, 2015 | Systemic Review | 9 Controlled Studies | iCBT is more effective than no-treatment condition. iCBT is as effective as face-to-face CBT. |
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Fuller et al.13, 2020 | Meta-analysis | 28 Controlled Studies | In all CBT group; primary outcome: Significant reduction of the impact of tinnitus on QOL. CBT vs no intervention: 14 studies. CBT vs audiological care: 3 studies. Secondary outcome: reduction is depression CBT vs TRT: 1 study. No secondary outcome. CBT vs active control (relaxation, information, Internet-based discussion forums): 16 studies. Secondary outcome: reduction in depression and anxiety. |
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Nolan et al.14, 2020 | Cross-sectional | 268 Patients | Reduction of TQ, QHS, BSI, and BDI-II. | ||
Yoga | Köksoy et al.15, 2018 | Clinical Trial | 12 Patients | Yoga practices reduce stress, handicap and severity of tinnitus. | |
Niedziałek et al.16, 2019 | Randomized Controlled Trial | 38 Patients | Significant decrease in 5 of 8 subscales of TFI global score (Intrusiveness, Sense of control, Sleep, Auditory, and Quality of life). | ||
Neurofeedback | Peter et al.18, 2019 | Review | TMS: to be used for tinnitus localization rather tinnitus suppression. tDCS, Transcranial random noise stimulation: qualify as a promising method in tinnitus treatment. Neurofeedback: should be further investigated as a treatment modality for tinnitus Vagus nerve stimulation: promising treatment option for tinnitus. Invasive brain stimulation: more research is needed. It will always be limited to a very select group because it is invasive. |
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Guillard et al.19, 2021 | Clinical Trial | 33 Patients | Significant decrease of the THI score. Significant increase of the alpha-band power within sessions. |
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Güntensperger et al.22, 2020 | Randomized Controlled Trial | 26 Patients | Significance reduction of tinnitus loudness and related distress (THI, TQ). An increase in the trained alpha/delta ratio. |
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Güntensperger et al.21, 2019 | Randomized Controlled Trial | 48 Patients | Significant reduction of tinnitus loudness and related distress in both groups. Significant increase in trained alpha/delta ratio over the course of training and follow-up period. |
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Emmert et al.23, 2017 | Randomized Controlled Trial | 14 Patients | Significant deactivation of the secondary auditory cortex until the last session for the continuous group vs intermittent feedback showed the strongest down-regulation in the first session. Decrease of the TFI scores that was not statistically significant. |
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Hypnosis | Ross et al.26, 2007 | Controlled Clinical Trial | 393 Patients | Significant improvement of the TQ and SF-36 scores in comparison to the waiting-list controls. | |
Maudoux et al.27, 2007 | Clinical trial | 49 Patients | Significant improvement of the THI score in all patients (60.23 before EH therapy to 16.9 at discharge). | ||
Yazıcı et al.28, 2012 | Controlled Clinical Trial | 39 Patients | Significant improvement of the THI and SF-36 scores. | ||
Brüggemann et al.36, 2021 | Meta-analysis | 3 Placebo-controlled Clinical Trials | Significant reduction in tinnitus severity. Significant improvement of anxiety, depression, and cognition. |
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Spiegel et al.37, 2018 | Review | 5 Placebo-controlled Clinical Trials |
EGb761 significantly superior to placebo in alleviating tinnitus and dizziness. | ||
Radunz et al.38, 2020 | Randomized Controlled Trial | 33 Patients | Significant improvement of the THI score with the individual HA and/or GB EGb71. HA were more effective in patients with shorter time to onset of tinnitus. GB alone or in association with HA was effective regardless of tinnitus duration. |
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Zinc | Jun et al.47, 2015 | Case-control | 2225 Patients | After adjustment of sex, age and hearing loss, no significant difference in zinc levels between a tinnitus population and a control population. Significant lower zinc levels in the most severe tinnitus group compared to the control group. |
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Berkiten et al.48, 2015 | Cross-sectional | 100 Patients | Patients in group III (between 61 and 78 years old) have significantly lower serum zinc levels. Significantly higher hearing thresholds of air conduction in zinc-deficient patients. Significantly higher Tinnitus Severity Index Questionnaire and loudness scores in zinc-deficient patients. |
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Coelho et al.49, 2013 | Randomized Controlled Trial | 116 patients | No significant improvement in THQ scores after zinc treatment or placebo. | ||
Person et al.50, 2016 | Systemic Review | 3 Randomized Controlled Trials | Overall, no significant improvement in tinnitus severity and loudness. No significant improvement in any secondary outcome (QOL, anxiety, and depression). | ||
Vitamin B and Antioxidants | Lee and Kim58, 2018 | Cross-sectional | 1,435 Patients |
Less intake of vitamin B2 is associated with tinnitus in middle-aged patients. Less intake of water, protein, and vitamin B3 is associated with tinnitus-related annoyance in elderly. It’s recommended to use vitamin B2 and B3 in combination with pharmacological or behavioral therapy. | |
Singh et al.59, 2016 | Randomized Controlled Trial | 40 Patients | Significant improvement in mean TSI score and VAS after vitamin B12 treatment in patients with tinnitus and cobalamin deficiency. | ||
Hameed et al.60, 2018 | Observational Cohort | 75 Patients | Supplementation with vitamin B complex improve the tinnitus severity, specifically in patients with tinnitus and without hearing loss. DPOAE changing amplitude can be used as a tool to assess the effect of vitamin B complex used in patient with tinnitus with or without hearing loss. |
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Dawes et al.61, 2020 | Cross-sectional | 34,576 Patients | Higher intake of vitamin B12 and protein is associated with reduced odds of tinnitus. Meanwhile, a high intake of calcium, iron, and fat were associated with increased odds of tinnitus. High intake of vitamin D, fruits and vegetables, and protein is associated with reduced likelihood of hearing difficulties. High fat intake was associated with hearing difficulties. |
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Ekinci et al.62, 2020 | Randomized Controlled Trial | 50 patients | Serum prolidase enzyme and oxidative stress might participate to the etiopathogenesis of tinnitus. | ||
Khan et al.63, 2007 | Clinical Trial | 20 patients | CoQ10 supply in patients with low CoQ10 levels, may decrease tinnitus. | ||
Melatonin | Albu and Chirtes66, 2014 | Randomized Controlled Trial | 60 Patients | In the intratympanic dexamethasone plus melatonin (compared to melatonin alone): Significant improvement in all of the following outcome measures: tinnitus loudness score, tinnitus awareness score, Tinnitus Handicap Inventory (THI), Pittsburgh Sleep Quality Index (PSQI) and Beck Depression Inventory (BDI). | |
Rosenberg et al.68, 1998 | Randomized Controlled Trial | 30 Patients | Statistically significant overall improvement among patients with high THI scores and/or difficulty sleeping taking melatonin when compared to placebo. | ||
Abtahi et al.69, 2017 | Randomized Controlled Trial | 70 Patients | THI scores were significantly reduced in the melatonin and sertraline groups, but the use of melatonin is more effective. | ||
Miroddi et al.70, 2015 | Review | 5 Clinical Studies | The authors were not able to confirm the effectiveness of melatonin in treating tinnitus, however, melatonin improved sleep disturbances associated to tinnitus. | ||
Merrick et al.71, 2014 | Review | Patient with tinnitus can benefit from melatonin through its antioxidant and sleep enhancement properties. | |||
Acupuncture | Tu et al.72, 2019 | Randomized Controlled Trial | 30 Patients | Significant reduction in THI in DA group greater than that in SA group. DA can modulate the autonomic nervous system by activating the sympathetic and parasympathetic nervous system balance. |
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Cai et al.73, 2019 | Clinical Trial | 54 Patients | Significant reduction in temperature differentials of both sides after acupuncture implying an even distribution of blood in both cochlea. | ||
Naderinabi et al.74, 2018 | Randomized Controlled Trial | 88 Patients | TSI and VAS significantly improved in all groups; however the differences by both measures were better with acupuncture compared to placebo at the end of the late sessions. | ||
Pang et al.75, 2019 | Review | 40 Randomized Controlled Trials | The 8 different methods of acupuncture are effective in treating tinnitus. The clinical effect from high to low is as follow: moxibustion acupuncture, moxibustion acupuncture combined with electroacupuncture, moxibustion acupuncture combined with supplementary medication, traditional acupuncture combined with supplementary medication, electroacupuncture combined with supplementary medication, electroacupuncture, traditional acupuncture, and medication-only treatment. |
Abbreviations 1: BDI-II= Beck Depression Inventory, BSI=Brief Symptom Inventory, CBT=Cognitive Behavioral Therapy, DA= Deep Acupuncture, DPOAE=Distortion product otoacoustic emissions, GB= Ginkgo Biloba, HA=Hearing Aid, iCBT=Internet-based CBT, PSQI=Pittsburgh Sleep Quality Index, SA=Shallow Acupuncture, SF-36=Health Survey, tDCS=Transcranial Direct Current Stimulation, TFI=Tinnitus Functional Index, THI=Tinnitus Handicap Inventory, THQ=Tinnitus Handicap Questionnaire, TMS=Transcranial Magnetic Stimulation, TQ= Tinnitus Questionnaire, TRT= tinnitus retraining therapy, TSI= Tinnitus Severity Index, QHS=Questionnaire on Hypersensitivity to Sound, QOL=Quality Of Life, VAS=Visual Analog Scale
Table 3:
Symptom | Alternative Medicine Interventions | Study | Study Nature | Sample Size | Key Findings |
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Hearing Loss |
Ginkgo Biloba | Koo et al.41, 2016 | Randomized Controlled Trial | 56 Patients | Association between systemic steroids and EGb761 showed no superiority in comparison with steroids alone in pure tone threshold. The words recognition score improved in combination therapy. |
Acupuncture | Zhang et al.76, 2015 | Meta-analysis | 12 Randomized Controlled Trials | Manual acupuncture combined with conventional medicine comprehensive treatment was better than conventional medicine alone in treating patients with SSNHL. | |
Chen et al.77, 2019 | Meta-analysis | 20 Randomized Controlled Trials | EA, EA + conventional medicine, and MA+ conventional medicine were superior to conventional medicine alone for the treatment of SSNHL. | ||
HBOT | Huang et al.82, 2021 | Randomized Controlled Trial | 102 Patients | IVS+HBOT: better hearing recovery rate compared to the control group within the first 7 days. No significant improvement of tinnitus. |
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Alimoglu et al.83, 2011 | Clinical Trial | 217 Patients | Patients receiving oral steroids + HBOT had higher chances to recover than patients receiving oral or IV steroids or HBOT alone. | ||
Rhee et al.84, 2018 | Meta-analysis | 19 Clinical Trials | Patients with severe to profound hearing loss may benefit from the adjunction of HBOT to conventional medical treatment. | ||
Bayoumy et al.85, 2019 | Review | 68 Studies | HBOT can be used as an optional therapy in patients with acute hearing loss (idiopathic or acoustic trauma). | ||
Eryigit et al.86, 2018 | Systemic Review | 16 Studies | No significant difference was found between the intervention and control groups. However, patients severe to profound hearing loss may benefit from the combination of steroids and HBOT. |
Abbreviations 3: EA=Electroacupuncture, HBOT=Hyperbaric Oxygen Therapy, IVS=Intravenous steroid SSNHL=Sensorineural Hearing Loss
Cognitive Behavioral Therapy
Cognitive behavioral therapy (CBT) is an active approach that includes a wide array of strategic interventions such as cognitive restructuring, behavioral activation, exposure, and problem-solving. It helps reduce emotional distress and increase adaptative behaviors, thus adopting a problem-solving strategy.6 Several studies evaluating CBT for tinnitus have demonstrated its effectiveness as an alternative approach.7,8,9
In a randomized double-blinded controlled study,10 tinnitus patients were allocated in two groups; the first one receiving CBT with sound-focused tinnitus retraining therapy, and the second group was provided standard audiological intervention. Patients assigned to the CBT showed a decrease in tinnitus severity and improvement in their quality of life (QOL). In another study, Beukes et al. concluded that internet-delivered CBT (iCBT) helped reduce tinnitus distress and associated difficulties (anxiety, depression, and insomnia), hence improving the QOL.11 Andersson reported that iCBT is as effective as face-to-face CBT.12 Furthermore, a smartphone-based CBT and customized sound therapy were found to be effective in treating tinnitus.7 Although in this study no significant improvement was reported in the Generalized Anxiety Disorder 7-item and Perceived Stress Scale, a significant reduction of Tinnitus Handicap Index (THI) –which measures tinnitus-related stress, anxiety, and QOL– was observed in the treatment group.7 Additionally, in a Cochrane systematic review, including 28 studies comparing CBT versus no intervention, audiological care, tinnitus retraining therapy, or any other active control, the authors concluded that CBT may be effective in reducing tinnitus negative impact on QOL and associated depression.13 In line with the previous results, Nolan et al. showed a highly significant reduction in tinnitus, hyperacusis, and concomitant psychological symptoms post-treatment with CBT.14 Based on the data, CBT is a valuable treatment option for the treatment of tinnitus.
Yoga
There are several studies demonstrating the benefits of yoga in patients suffering from tinnitus.15,16,17 The first study by Köksoy et al. showed that yoga practices reduce tinnitus severity and tinnitus stress score. Thus, practicing yoga improves the symptoms of tinnitus and QOL, and reduces stress and anxiety.15 Another study in 25 patients with chronic tinnitus assessed 12-week of yoga training compared to a control group of 13 patients. The yoga group improved on the tinnitus functional index (TFI) global score.16 Both studies were limited by the lack of longer term follow-up and small sample sizes. Gazbare et al. performed a randomized controlled trial comparing the effect of yogasanas (yoga postures) to gaze stabilization and habituation exercises in vestibular dysfunction. The authors concluded that both practices were effective in reducing dizziness. Furthermore, greater improvement in the Motion Sensitivity Quotient was seen with yogasanas and greater improvement in the Dizziness Handicap Inventory (DHI) with stabilization and habituation exercises.17 Based on the limited available data, yoga may have a beneficial effect on dizziness and tinnitus but more confirmatory studies are needed to evaluate their efficacy.
Neurofeedback
Several neuromodulation techniques18, including neurofeedback, have been used to target tinnitus.19 Neurofeedback is a form of biofeedback that measures the patient’s brain activity, then generates audio-visual feedback in real-time so the patient can reinforce his/her brain activity consciously via operant conditioning.20 Interestingly, as reported in a randomized controlled study, an increase in alpha activity via neurofeedback training led to a decrease in tinnitus-related distress and loudness.21,22 Similar results were found in a randomized controlled study comparing continuous versus intermittent neurofeedback. This study showed that continuous feedback is superior to intermittent feedback in the long term; the TFI score significantly improved after all the sessions and patients felt more relaxed.23 Targeting larger tinnitus-implicated areas in the brain might lead to even better outcomes, therefore, individualized neurofeedback training could potentially be a promising therapeutic option in the treatment of tinnitus.24
Hypnosis
Although the studies testing the effect of hypnosis on patients with tinnitus have been scarce, the few available ones demonstrated a positive result in the treatment of troublesome tinnitus. The largest study using Ericksonian Hypnosis (EH) included 393 patients suffering from subacute and chronic tinnitus that were treated within an inpatient closed-group over 28 days, and compared to a waiting-list control group. The severity of the tinnitus was measured by Tinnitus Questionnaire (TQ) up to 12-month follow-up. Considering that the minimal clinically important difference of TQ changes was estimated to a reduction of at least 5 points25, significant improvement in TQ was observed compared to the waiting-list group with a mean reduction of 15.9 and 14.1 in the subacute and chronic tinnitus group, respectively.26 Two other trials by Maudoux et al.27 and Yazıcı et al.28, verifying the effect of EH in an outpatient setting, have achieved similar results with less overall session time and with a significant reduction in THI scores compared to admission, thus showing hypnosis efficacy. This area is still under-researched; however, preliminary results are promising.
Physical Therapy
Studies have shown that patients with vestibular dysfunction improve with vestibular rehabilitation (VR).29,30,31 In a systemic review, with 1876 patients, Regauer et al. concluded that VR in any modality (Table 2), except Tai Chi and manual therapy, was superior to usual care in treating older patients with vertigo, dizziness, and balance disorders.32 Moreover, Liu et al. investigated the effect of VR on brain activity in patients with vestibular migraine (VM), using resting-state functional MRI. The results showed a significant decrease in the DHI scores and an increase in the Short Form Health Survey (SF-36) scores after VR training. The amplitude of low-frequency fluctuation was significantly higher in the left posterior cerebellum compared to baseline in patients with VM, asserting that the cerebellum may play a role in vestibular compensation.33 These studies demonstrated the benefits of VR in improving vestibular symptoms and QOL.
Table 2:
Symptom | Alternative Medicine Interventions | Study | Study Nature | Sample Size | Key Findings |
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Vertigo |
Yoga | Gazbare et al.17, 2021 | Randomized Controlled Trial | 32 Patients | Both groups reduced symptoms of dizziness. Yogasanas: better improvement in MSQ. Gaze stabilization and habituation exercises : better improvement in DHI. |
Physical Therapy | Brown et al.29, 2006 | Case-series | 48 Patients | Statistically significant improvement after physical therapy on the ABC, DHI, DGI, the Timed Up & Go test, and the FTSTS Test. | |
Whitney et al.30, 2000 | Case-series | 39 Patients | Statistically significant improvement after physical therapy on the DHI, ABC, PDS, the DGI, and the CS. | ||
Brown et al.31, 2001 | Case-series | 24 Patients | Statistically significant improvement after physical therapy on the DHI, ABC, DGI, Timed “Up and Go” measures, and the CS scores. |
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Regauer et al.32, 2020 | Systematic Review | 20 Randomized and 2 Non-randomized Controlled Trials | Interventions included: VR, CAVR, TCVR, CRM, and MT. VR and VR in addition to CRM and MT are effective in treating patients with VDB. |
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Liu et al.33, 2020 | Clinical Trial | 19 Patients | Significant decrease of the DHI and HAMA scores. Significant increase of the ALFF values in the left posterior cerebellum. |
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Ginkgo Biloba | Sokolova et al.42, 2014 | Randomized Controlled Trial | 160 Patients | Both drugs were similarly effective in the treatment of vertigo, but EGb761 was better tolerated. | |
Hamann et al.43, 2006 | Systematic Review | Preclinical and double-blind clinical studies show that EGb761 promotes compensation and is effective in the treatment of vertigo syndromes |
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Lindner et al.44, 2019 | Preclinical Study | 40 Rats |
Group A: significant reduction of nystagmus scores, of postural asymmetry, and increased motility in the open field when compared to controls. Groups B and C: fast recovery of postural asymmetry. |
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Ginkgo Biloba in combination with Neurofeedback | Decker et al.45, 2021 | Randomized Controlled Trial | 120 Patients | Statistically significant improvement in the fall risk in balance-related situations and proprioceptive components of the gSBDT-CS in the active group. | |
Zinc | Ferreira et al.51, 2009 | Case-control | 16 Patients | Hypozincemia affect the function of the vestibulo-ocular, vestibulo-cerebellar, and vestibula-cortical pathways. | |
Acupuncture | Chiu et al.78, 2015 | Randomized Controlled Trial | 60 Patients | Acupuncture reduced discomfort and VAS of both vertigo and dizziness after 30min treatment in the emergency department. |
Abbreviations 2: ABC=Activities-Specific Balance Confidence Scale, ALFF=Amplitude of low-frequency fluctuations, CAVR= Computed-assisted vestibular rehabilitation, CRM=Canalith Repositioning Maneuvers, CS=Composite Score, DGI=Dynamic Gait Index, DHI=Dizziness Handicap Inventory, FTSTS=Five Times Sit-to-Stand, gSBDT-CS=geriatric Standard Balance Deficit Test Composite Score, HAMA=Hamilton Anxiety Scale MSQ=Motion Sensitivity Quotient, MT=Manual Therapy, PDS=Perception of Dizziness Symptoms, TCVR= Tai Chi vestibular rehabilitation, VR=Vestibular Rehabilitation, VAS=Visual Scale Analog, VDB=Vertigo, Dizziness and Balance disorders
Supplements
Ginkgo Biloba
There are several contradictory studies on the effectiveness of Ginkgo Biloba (GB) as a treatment for tinnitus. The active ingredient has been identified as EGb761.3 In the studies that do not show superiority of GB over placebo, the herbal supplement was used in its non-standardized form (other than GB extract EGb761) or with a lower dose than clinically indicated (<240 mg twice daily).34 Otherwise, most studies have shown the efficacity of GB extract EGb761 as a treatment for patients with tinnitus.35,36,37,38 A randomized placebo-controlled trial investigating the benefit of EGb761 in dementia patients with tinnitus, showed a direct positive effect on the severity of tinnitus, and an indirect positive effect by improving depression, anxiety, and cognition.36 In a meta-analysis of five trials, Spiegel et al. reported that EGb761 displayed significant therapeutic outcomes over placebo after 20 weeks of treatment in terms of tinnitus and dizziness in patients with dementia (at the end of the treatment, the 11-point box scales for tinnitus and dizziness were reduced by 1.06 and 0.77, respectively).37 EGb761 improves cerebral and cochlear blood flow39 as well as mitochondrial functioning40– the desired effect in elderly patients with impaired perfusion and mitochondrial function. Furthermore, Randuz and colleagues demonstrated an improvement in tinnitus severity and loudness after a 3-month period of treatment with GB and/or hearing aids, with no synergism between the treatments.38
EGb761 was also tested in a randomized placebo-controlled trial in patients with idiopathic SSNHL. Although adjuvant systemic steroids with EGb761 showed no superiority in comparison with steroids alone in pure tone threshold, the words recognition score improved in combination therapy.41 Finally, in a randomized, double-blinded trial, Sokolova et al. found that EGb761 was as effective as betahistine in the treatment of unspecified vertigo in all outcome measures.42 EGb761 was also found to be superior to placebo in vestibular and non-vestibular vertigo. This superiority was measured by different means such as vertigo score (intensity, duration, frequency), global assessment of patients (VAS), caloric test, and sway amplitude in the cranio-corpography and posturography.43 Additionally, following a unilateral labyrinthectomy in rats, oral supplementation with EGb761 was shown to be effective on the compensation of static and dynamic vestibular function (nystagmus, postural asymmetry, and locomotor behavior).44 A bimodal therapy consisting of the combination of EGb761 with vibrotactile neurofeedback, resulted in improvement in age-related vertigo and dizziness after 6 weeks of treatment. In addition, no safety issues were reported.45 These results should be confirmed in future clinical trials.
Zinc
Studies have shown that the inner ear, especially the stria vascularis, has a high zinc content, which protects the cochlea from injury due to reactive oxygen species, and that a low serum level of zinc could lead to otologic disorders, such as tinnitus, imbalance, and hearing loss.34,46 In a large study, using data from the Korea National Health and Nutrition Examination Survey, Jun et al. found that serum zinc levels were significantly lower in patients with severe tinnitus only and that low serum zinc levels was not correlated to tinnitus in the other sub-population (mild tinnitus, moderate tinnitus, and control group).47 Similarly, Berkiten et al. showed by using the tinnitus severity index questionnaire that lower serum zinc levels were associated with increased severity and loudness of tinnitus. In addition, they demonstrated that serum zinc levels decrease as age increases and that an increase in hearing thresholds is associated with low serum zinc levels.48 In two randomized placebo-controlled trials, zinc supplementation was not more effective than placebo in treating elderly patients with tinnitus.49,50
In a study by Ferreira et al., which included patients with zinc deficiency, it was demonstrated that hypozincemia possibly affected the function of vestibulo-ocular, vestibulo-cerebellar, and vestibulo-cortical pathways when tested using videonystagmography. The authors suggested that zinc may affect the functioning of the vestibular system.51 Overall, the advantage of supplementing of zinc in the treatment of migrainous ear disorders remains an item of debate and requires further assessments.
Vitamin B and Antioxidants
Recent studies have shown a correlation between migraine headache and various vestibular disorders (Meniere’s disease (MD)52, benign paroxysmal positional vertigo53, and Mal de Debarquement syndrome54). As such, it has been shown that treating MD with a migraine diet and lifestyle modifications (preventing dehydration, starvation, and sleep disturbances, avoiding certain foods such as chips, cheese, chocolate, nuts, processed meats, certain fruits, and pickled fruits or vegetables), as well as supplementation with vitamin B2 and Magnesium can control vestibular and cochlear symptoms.55 Similarly, patients suffering from tinnitus can benefit by preventing dehydration and avoiding certain foods such as caffeine, alcohol, processed meats, monosodium glutamate (found in soy sauce or pickled foods), aspartame, avocado, and chocolate.56,57 Furthermore, Lee and Kim reported that less vitamin B2 intake in young ages was associated with tinnitus, while less intake of vitamin B3 in the elderly was significantly associated with tinnitus-related annoyance. The authors recommended that supplementation with vitamin B2 and B3 might be considered in conjunction with conventional pharmacological therapy or CBT, while managing tinnitus in patients.58 Vitamin B12 is an essential cofactor for myelin sheath formation, thus preventing neuronal dysfunction peripherally and centrally. Seidman and Babu believe that there might be an association between vitamin B12 deficiency and increased prevalence and severity of tinnitus in elderly, as supplementation with vitamin B12 showed some relief.4 Consistently, in a randomized, double-blinded clinical trial, patients with tinnitus and cobalamin (vitamin B12) deficiency, receiving vitamin B12, showed a significant improvement in the visual analog scale (VAS) and tinnitus severity index (TSI) after treatment with vitamin B12.59 It has been also demonstrated that following one month of treatment with vitamin B complex, the amplitude of the distortion product otoacoustic emissions increased with clinical improvement, especially in patients with tinnitus.60 Similarly, using the UK Biobank resource, Dawes et al. conducted a study to evaluate the role of diet in tinnitus and hearing disorders. There were associations between a high intake of vitamin B12 and protein with a reduced likelihood of tinnitus, while high calcium, iron, and fat intakes were associated with an increased likelihood of tinnitus.61
Besides B vitamins, and based on the theory that reactive oxygen species contributed to tinnitus, Ekinci and Kamasak supported the use of antioxidants.62 A clinical trial demonstrated that supplementing patients with low plasma Coenzyme Q10 (CoQ10) levels and chronic tinnitus with CoQ10 may decrease tinnitus.63 In addition, it has been reported in two meta-analyses that CoQ10 supplementation significantly reduced the duration and frequency of migraine headache attacks, without a significant effect on severity, when compared with the control group.64,65 Patients with tinnitus, vertigo, and poor hearing may benefit from supplementation with some vitamins and certain antioxidants.
Melatonin
The precise mechanism of action of melatonin on tinnitus is not well known, but it is thought that its favorable outcomes are possibly related to the regulation of the labyrinthine perfusion, reduction of the muscular tone and sympathetic drive, anti-depressive effects, and antioxidant effects.66,67 Rosenberg et al. performed the first randomized, double-blinded, placebo-controlled trial evaluating the efficacy of melatonin as a treatment for tinnitus. They found that patients with high THI scores and/or difficulty sleeping would benefit from melatonin.68 Abtahi and colleagues demonstrated that melatonin may outperform sertraline in treating tinnitus. They found that after 3 months of 3 mg melatonin once daily or 50 mg sertraline once daily, the THI scores significantly decreased in both groups, however, the decrease was significantly more for melatonin (reduction of THI score from 45 to 30 in melatonin group and from 45 to 37 in sertraline group). These results asserted that both drugs are effective, but melatonin was more helpful especially since no side effects, 69 apart from nightmares have been reported to date.34 Along with these findings, Albu and Chirtes demonstrated that after 3 months of treatment, patients receiving intratympanic (IT) dexamethasone plus melatonin or only melatonin attained statistically significant improvement on the tinnitus loudness score, tinnitus awareness score, THI, Pittsburgh Sleep Quality Index and Beck Depression Inventory, favoring the IT dexamethasone plus melatonin in patients with acute unilateral tinnitus.66 Therefore, it would be desirable to redirect the available evidence through high-quality clinical trials, especially given that in all studies the efficacy of melatonin in tinnitus and associated sleep disturbances has been recognized.70,71 It is likely that improvement of sleep may be the primary reason melatonin improves quality of life in patients with tinnitus. Melatonin may be beneficial for patients with tinnitus who also suffer from sleep-onset delay.
Acupuncture
Acupuncture has been widely used to treat tinnitus in Eastern Asia countries.34 It seems that deep acupuncture (needles inserted approximately 10 mm to 30 mm deep) improved tinnitus symptoms by modulating the sympathetic and parasympathetic nervous system balance.72 Another study using infrared thermography test pre and post acupuncture treatment in patients with tinnitus showed that the efficacy of acupuncture is due to an improvement of cochlear blood flow in both ears even if acupuncture was applied on one side.73 As such, multiple studies have demonstrated the superiority of acupuncture as a treatment for tinnitus when compared to placebo or conventional medication.74,75 Additionally, two meta-analyses showed a better effect of acupuncture combined with conventional medicine (such as systemic or intratympanic steroids, hyperbaric oxygen, and vasodilators) than conventional medicine alone in the treatment of SSNHL and sudden deafness76,77 Finally, a controlled clinical trial demonstrated that acupuncture reduces the discomfort and VAS of dizziness and vertigo, after 30 minutes of treatment in the emergency department.78
Hyperbaric Oxygen Therapy
Cochlear migraine (fluctuating or SSNHL) is a new concept that was first described in 2018.79,80 One of the etiological hypothesis has been attributed to an abnormal blood flow to the cochlea.81 Thus, based on the principle of hypoxia of the inner ear, several studies supported the implementation of hyperbaric oxygen therapy (HBOT) in combination with steroids as a treatment for SSNHL82,83,84,85, specifically in patients with severe or profound hearing impairment.86 Currently, there is mixed evidence in support of HBOT for SSNHL. If there is a benefit, it is best provided early after the onset.
Conclusions
Several CIM treatment options may be beneficial for migrainous tinnitus, vertigo, and ear symptoms. Although many physicians may be hesitant to consider these treatment modalities, CIM should be used as a complementary approach combined with conventional treatment, especially with patients who did not sufficiently benefit from medical therapy. More randomized controlled studies are needed to define the efficacy of the various CIM therapies on otologic migraine. These studies are best performed by collaboration of neurotologists and complementary and integrative medicine specialists. In general, most treatments are well-tolerated with limited side effects. Therefore, CIM should be in the repertoire of every clinician treating otologic migraine.
Key Points.
Migraine is a chronic disorder that frequently coexists with vestibular and neuro-otological symptoms leading to significant physical and psychological disabilities including tinnitus and hearing loss.
The evidence currently encourages the use of cognitive behavioral therapy and supplements for the treatment of tinnitus and vestibular rehabilitation for vertigo.
Based on the review results, complementary and integrative medicine should undergo further high-quality clinical trials to obtain more definitive data to translate these therapies into routine recommendations for patients.
Financial Disclosure:
Mehdi Abouzari is supported by the National Center for Research Resources and the National Center for Advancing Translational Sciences, National Institutes of Health, through Grant TL1TR001415.
Footnotes
Conflicts of Interest: Hamid R. Djalilian holds equity in MindSet Technologies, Elinava Technologies, and Cactus Medical LLC. He is a consultant to NXT Biomedical.
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